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BACKGROUND The " long/short"polymorphism ( 5HTTLPR ) in the promoter of the serotonin transporter gene ( SLC6A4 ) has been proposed as a pharmacogenetic marker for antidepressant efficacy . Some but not all studies have found that the short form of 5HTTLPR ( S allele ) results in decreased efficacy of selective serotonin reuptake inhibitors . OBJECTIVE To determine if the 5HTTLPR polymorphism influences the efficacy and tolerability of mirtazapine and paroxetine hydrochloride , 2 frequently prescribed antidepressants with differing pharmacologic profiles , in geriatric depression . DESIGN Double-blind , r and omized 8-week study . SETTING Eighteen academic and private outpatient clinics . PATIENTS We evaluated 246 cognitively intact patients 65 years or older with major depression . INTERVENTIONS Antidepressant therapy with 15 to 45 mg/d of mirtazapine ( n = 124 ) or 20 to 40 mg/d of paroxetine ( n = 122 ) . MAIN OUTCOME MEASURES The Hamilton Depression Rating Scale-17 and Geriatric Depression Scale , severity of adverse events and dosing compliance indexes , and discontinuations due to adverse events . Outcome measures were stratified according to 5HTTLPR genotypes . RESULTS Geriatric Depression Scale scores indicated that S allele carriers treated with paroxetine showed a small impairment in antidepressant response . Among mirtazapine-treated patients , there was little indication that the 5HTTLPR genotype affected antidepressant efficacy . However , the 5HTTLPR polymorphism had a dramatic effect on adverse events . Among paroxetine-treated subjects , S allele carriers experienced more severe adverse events during the course of the study , achieved significantly lower final daily doses , and had more discontinuations at days 14 , 21 , 28 , 42 , and 49 . Surprisingly , among mirtazapine-treated subjects , S allele carriers had fewer discontinuations due to adverse events , experienced less severe adverse events , and achieved higher final daily doses . CONCLUSIONS These results support the hypothesis that the S allele of 5HTTLPR at the SLC6A4 locus is associated with a poor outcome after treatment with selective serotonin reuptake inhibitors . However , the major effect was on the tolerability of these drugs rather than efficacy . Results from mirtazapine-treated patients indicate that the effect of this polymorphism on outcome may depend on the mechanism of antidepressant action Abstract Introduction : Depression is a major global problem associated with large medical , sociological and economic burdens . Mirtazapine ( Remeron ® , Organon NV , The Netherl and s ) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression . However , this agent has not yet been tested in patients with severe depression alone . Objective : To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression ( ≥25 points on the first 17 items of the Hamilton Depression Rating Scale [ HDRS-17 ] ) . Methods : In this double-blind study , 297 severely depressed patients were r and omised to receive mirtazapine 15–60 mg/day ( n = 147 ) or fluoxetine 20–40 mg/day ( n = 152 ) for 8 weeks . 294 subjects were actually treated and 292 included in the intent-to-treat population . Symptom severity was measured by the HDRS-17 , Montgomery-Asberg Depression Rating Scale ( MADRS ) and Clinical Global Impression ( CGI ) rating scale . Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Question naire and the Quality of Life , Enjoyment and Satisfaction Question naire . Adverse events were recorded throughout the study . Results : No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point ; both treatments were associated with large ( ∼15 points ) decreases by study end . However , more mirtazapine-treated patients tended to exhibit a ≥50 % decrease in HDRS score ( significant at day 7 ; 9.0 % vs 0.7 % , p = 0.002 ) . Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores ( −10.9 vs −8.5 , p = 0.006 ) and the proportion of patients with ≥50 % decrease in MADRS score ( 21.4 % vs 10.9 % , p = 0.031 ) . On the CGI , the proportion of ‘ much/very much improved ’ patients tended to be greater with mirtazapine ( significant at day 7 ; 9.7 % vs 3.4 % , p = 0.032 ) . No significant between-group differences were observed for the majority of quality -of-life measures . However , mirtazapine produced significantly better improvements on ‘ sleeping assessment 1 ’ ( 14.9 ± 5.2 vs 13.7 ± 5.4 , p = 0.028 ) and ‘ sleeping assessment 2 ’ ( p = 0.013 ) than fluoxetine . Both agents were generally well tolerated  but mirtazapine-treated patients experienced a mean weight gain of 0.8 ± 2.7 kg compared with a mean decrease in weight of 0.4 ± 2.1 kg for fluoxetine-treated patients ( p < 0.001 ) . Conclusions : Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression Modulations of serotonergic and noradrenergic systems are thought to be critical to the therapeutic effect of most antidepressants , and their efficacies have been shown to depend on a functional polymorphism within the promoter region of the serotonin transporter gene ( 5-HTTLPR ) . Mirtazapine has a dual-action profile , combining the enhancement of the noradrenergic neurotransmitter system with specific actions on particular serotonergic receptor subtypes . The goal of this study was to eluci date whether the 5-HTTLPR polymorphism is associated with the mirtazapine antidepressant response in subjects with major depressive disorder ( MDD ) . One hundred and one MDD patients were evaluated during 4 weeks of mirtazapine treatment . The severity of depression was assessed with the 21-item Hamilton Depression Rating scale , and the 5-HTTLPR genotypes in the patients were determined using the polymerase chain reaction . Our results showed that responses at the 2nd and 4th weeks were significantly better for the s/s genotype of the 5-HTTLPR polymorphism than for l-allele carriers . These results support our hypothesis that the response to noradrenergic and specific serotonergic antidepressants is significantly associated with the 5-HTTLPR polymorphism OBJECTIVE Authors studied the efficacy and tolerability of mirtazapine and paroxetine in elderly patients with major depression during an acute phase ( 8 weeks ) and an extension phase ( 16 weeks ) . METHODS Patients with major depression and without dementia , at least 65 years old , were eligible ; they were r and omized to mirtazapine or paroxetine once daily , with doses increasing over 42 days . Efficacy was assessed with the Ham-D and Clinical Global Impressions Scale , and tolerability was assessed from adverse events . RESULTS Of 255 patients r and omized , 126 on mirtazapine and 120 on paroxetine were included in the efficacy analysis . Differences favoring mirtazapine were observed for the mean change from baseline in Ham-D-17 score . Other significant differences were in the proportion of patients classified as responders ( 50 % decrease from baseline Ham-D-17 scores ) at Day 14 and in remission ( Ham-D-17 score of 7 or less ) at Day 42 . The median time to response was 26 days in the mirtazapine group and 40 days in the paroxetine group . The mirtazapine group also showed more reduction in Ham-D Factor I ( Anxiety/Somatization ) and Factor VI ( Sleep Disturbance ) scores . Efficacy of both drugs was maintained during the extension phase . Patients on paroxetine were more likely to discontinue therapy in the acute phase because of adverse events . CONCLUSION During the first weeks of treatment , antidepressant effects were more pronounced in the mirtazapine group , suggesting that mirtazapine has an earlier onset of action . Mirtazapine also demonstrated a better tolerability profile and represents a valuable option for the treatment of depression in elderly patients Abstract Aim : Sexual dysfunction , common in schizophrenia , may be further exaggerated by antipsychotics , especially those of First Generation ( FGAs ) , and antidepressants , such as Selective Serotonin Reuptake Inhibitors ( SSRs ) . Mirtazapine , an antidepressant characterized by its different action mechanism compared with that of the majority of other antidepressants , may improve SSRI-induced sexual dysfunction in patients with depression . It is unknown , however , whether mirtazapine improves sexual functioning in schizophrenia . Methods : This study r and omly assigned FGA-treated patients with schizophrenia to receive either an add-on  mirtazapine ( n = 20 )  or a placebo  ( n = 19 ) for 6 weeks . Sexual functioning was prospect ively measured using five relevant items from the Udvalg for Kliniske Undersogelser side-effect rating scale ( UKU-SERS ) . Results : Orgasmic function improved with statistical significance in the mirtazapine group ( p = .03 ) , with no changes in any other sexual functions in either group . Conclusion : Add-on mirtazapine appears to relieve orgasmic dysfunction in FGA-treated patients with schizophrenia This r and omized , multicenter , double-blind study was design ed to compare specifically the onset of antidepressant action of mirtazapine orally disintegrating tablets ( ODT ) with venlafaxine extended-release ( XR ) formulation in out patients with major depression . Both treatments were administered in a rapidly escalating dosing regimen . Target doses ( mirtazapine ODT , 45 mg OD ; venlafaxine XR , 225 mg OD ) were reached by day 6 of treatment . On the primary efficacy parameter [ the average of the change in HAM-D ( 17-item ) total score on days 5 , 8 , 11 , and 15 ] , mirtazapine ODT was significantly superior to venlafaxine XR ( P = 0.008 ) . In addition , calculating the HAM-D score without the sleep items result ed in significant reductions in favor of mirtazapine ODT on days 8 ( P = 0.006 ) and 11 ( P = 0.037 ) . The proportion of responders ( HAM-D decrease of ≥50 % from baseline ) was higher in the mirtazapine ODT group on all assessment days , being significant on days 8 ( P = 0.002 ) , 11 ( P = 0.004 ) , and 22 ( P = 0.027 ) . More patients in the mirtazapine ODT group achieved remission ( HAM-D total score of ≤7 ) up to day 29 , and the difference was statistically significant on day 15 ( P = 0.016 ) . Significant differences in favor of mirtazapine ODT were evident in the CGI of change on days 8 ( P = 0.019 ) , 11 ( P = 0.004 ) , and 15 ( P = 0.031 ) , and the CGI of severity on days 8 ( P = 0.014 ) and 11 ( P = 0.033 ) . Both treatments were well tolerated . These results indicate that mirtazapine ODT has a faster onset of antidepressant efficacy  than venlafaxine XR in patients with major depressive disorder , and that this effect is independent of its sleep-improving properties Cancer patients are commonly associated with various physical and psychological symptoms . In palliative setting , the aims are to relieve those symptoms , improve quality of life , and increase medication adherence among cancer patients . Antidepressants are generally accepted for the treatment of depression among patients with or without cancer . Some other potential benefits of the antidepressants have been reported in cancer patients . OBJECTIVE This study aims to review the use of antidepressants for physical and psychological symptoms in cancer patients . RESULTS Our findings showed the mixed result of positive and negative findings in various symptoms associated with cancer patients . These studies are categorised according to the hierarchy of evidence from high to low level , namely r and omised controlled trials , cohort studies , case-control studies , case series , case reports , as well as other type of publications . The majority of antidepressants used in cancer patients seem to be beneficial for the treatment of depression , anxiety , hot flashes and other symptoms such as sexual dysfunction , fatigue , nicotine dependence , vasomotor symptoms , executive functions , sleep problems , pruritus , as well as for hypochondriasis . While fluoxetine was found to be associated with the reduction of antiemetic property in ondansetron , mirtazapine was identified to be a good alternative in treating nausea and cachexia among cancer patients . CONCLUSION More research studies with adequate statistical power are warranted to vali date the use of antidepressants among cancer patients in treating these physical and psychological symptoms Genetic variation at the FKBP5 locus has been reported to affect clinical outcomes in patients treated with antidepressant medications  in several studies . However , other reports have not confirmed this association . FKBP5 may regulate the sensitivity of the hypothalamic – pituitary – adrenal axis . We tested two  FKBP5 single nucleotide polymorphisms ( rs1360780 and rs3800373 ) in a sample of 246 geriatric patients treated for 8 weeks in a double‐blind r and omized comparison trial of paroxetine and mirtazapine .  These two polymorphisms had previously been reported to predict efficacy in depressed patients treated with selective serotonin reuptake inhibitors such as paroxetine , and those treated with mirtazapine , an agent with both serotonergic and noradrenergic actions . However , we found no significant associations between these FKBP5 genetic variants and clinical outcomes . Neither mean Hamilton Depression Rating Scale scores nor time to remission or response were predicted by FKBP5 genetic variation . These results suggest that FKBP5 is unlikely to play a major role in determining antidepressant treatment outcomes in geriatric patients . © 2009 Wiley‐Liss , Objectives : Although antidepressant medications are effective , they have a delayed onset of effect . Mirtazapine , an atypical antidepressant is an important option for add-on therapy in major depression . There is insufficient data on mirtazapine in Indian population ; hence this study was design ed to study the add-on effect of low-dose mirtazapine with selective serotonin reuptake inhibitors ( SSRIs ) in major depressive disorder ( MDD ) in Indian population . Material s and Methods : In an open , r and omized study , 60 patients were divided into two groups . In Group A ( n=30 ) patients received conventional SSRIs for 6 weeks . In Group B ( n=30 ) patients received conventional SSRIs with low-dose mirtazapine for 6 weeks . Patients were evaluated at baseline and then at 1 , 2 , 3 , 4 , 5 , and 6 weeks . Results : There was significant improvement in Hamilton Depression Rating Scale ( HDRS ) , Montgomery and Asberg depression rating scale ( MADRS ) scores ( P<0.05 ) in both groups . Mirtazapine in low dose as add on therapy showed improvement in scores , had earlier onset of action , and more number of responders and remitters as compared to conventional treatment ( P<0.05 ) . No serious adverse event was reported in either of the groups . Conclusion : Low-dose mirtazapine as add-on therapy has shown better efficacy , earlier onset of action and more number of responders and remitters as compared to conventional treatment in MDD in Indian patients This multinational , r and omized , double-blind study was specifically design ed to prospect ively compare the onset of antidepressant efficacy of mirtazapine orally disintegrating tablets and sertraline at dosages commonly used in clinical practice . A total of 345 patients with major depressive episode ( DSM-IV ) received mirtazapine ( 30–45 mg/d ) or sertraline ( 50–150 mg/d ) for 8 weeks . Mirtazapine was administered in the newly developed fast dissolving , orally disintegrating tablet formulation . Assessment s were performed at baseline and on days 4 , 7 , 10 , 14 , 28 , 42 , and 56 . The primary efficacy variable ( mean absolute change from baseline in the Hamilton Depression Rating Scale [ HAMD ] total score [ 17 items ] ) showed that mirtazapine was significantly ( P < 0.05 ) more effective than sertraline at all assessment s during the first 2 weeks of the study . After this time , HAMD total scores were similar in both groups . These findings were supported by analysis of the HAMD response rate ( ie , ≥50 % reduction in HAMD total score from baseline ) , HAMD remission rate ( HAMD total score of ≤7 ) , and the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . Both treatments were well tolerated . In addition , mirtazapine had a greater effect  than sertraline  on sexual functioning . In conclusion , this first prospect i ve onset of action study using the orally disintegrating tablet indicates that mirtazapine has a faster onset of therapeutic effect  than sertraline . The orally disintegrating tablet formulation of mirtazapine used in this study is known to enhance the convenience and compliance by the patient OBJECTIVE Various classes of antidepressant medications generally induce remission of major depressive disorder  in only about one-third of patients . In a previous study using mirtazapine or paroxetine alone or in combination from treatment initiation , the rate of patients who remitted within a 6-week period was twice that of patients using either drug alone . In this double-blind study , the authors sought to produce evidence for the superiority of different combinations of antidepressant drugs from treatment initiation . METHOD Patients ( N=105 ) meeting DSM-IV criteria for major depressive disorder were r and omly assigned to receive , from treatment initiation , either fluoxetine monotherapy ( 20 mg/day ) or mirtazapine ( 30 mg/day ) in combination with fluoxetine ( 20 mg/day ) , venlafaxine ( 225 mg/day titrated in 14 days ) , or bupropion ( 150 mg/day ) for 6 weeks . The primary outcome measure was the Hamilton Depression Rating Scale ( HAM-D ) score . RESULTS The overall dropout rate was 15 % , without notable differences among the four groups . Compared with fluoxetine monotherapy , all three combination groups had significantly greater improvements on the HAM-D. Remission rates ( defined as a HAM-D score of 7 or less ) were 25 % for fluoxetine , 52 % for mirtazapine plus fluoxetine , 58 % for mirtazapine plus venlafaxine , and 46 % for mirtazapine plus bupropion . Among patients who had a marked response , double-blind discontinuation of one agent produced a relapse in about 40 % of cases . CONCLUSIONS The combination treatments were as well tolerated as fluoxetine monotherapy and more clinical ly effective . The study results , which add to a growing body of evidence , suggest that use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication Objective : To examine the antidepressant efficacy of a dual-acting antidepressant ( mirtazapine ) in patients with post-myocardial infa rct ion ( MI ) depressive disorder . Antidepressants used in post MI trials with a r and omized , double-blind , placebo-controlled design have been restricted to selective serotonin reuptake inhibitors ( SSRIs ) . Antidepressant effects have been limited . Methods : In a prospect i ve multicenter study , 2177 patients with MI were evaluated for depressive disorder during the first year post MI . Ninety-one patients who met the Diagnostic and Statistical Manual of Mental Disorders , 4th Edition ( DSM-IV ) criteria for major or minor depressive disorder were r and omized to a 24-week , double-blind , placebo-controlled trial . Antidepressant efficacy was tested using last-observation-carried-forward procedure and repeated measurements analysis using the SPPS mixed models approach , with as primary outcome reduction in depressive symptomatology on the 17-item Hamilton-Depression Rating Scale ( Ham-D ) , and secondary outcomes the Beck Depression Inventory ( BDI ) and depression subscale of the Symptom Check List 90 items ( dSCL-90 ) as well as the Clinical Global Impression ( CGI ) scale . Results : Using the “ last observation carried forward ” ( LOCF ) method , mirtazapine did not show to be superior to placebo on the Ham-D , but did on the BDI , dSCL-90 , and CGI scale over the acute treatment phase of 8 weeks ( n = 91 ) . Using mixed models analysis over the entire 24 weeks of treatment ( n = 40 ) , we did find a significant difference favoring mirtazapine to placebo on the Ham-D , BDI , and CGI , but on the dSCL-90 , this difference was not significant . Conclusions : This trial shows efficacy of mirtazapine on primary and secondary depression measures . Mirtazapine seems to be safe in the treatment of post-MI depression . MI = myocardial infa rct ion ; RCT = r and omized controlled trial ; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders ; CAD = coronary artery disease ; SSRI = selective serotonin reuptake inhibitors ; TCA = tricyclic antidepressant ; Ham-D = Hamilton-Depression Rating Scale ; BDI = Beck Depression Inventory ; CGI = Clinical Global Impression ; dSCL-90 = Symptom Check List 90 items , depression subscale ; SES = st and ardized effect size BACKGROUND The necessity of antidepressant continuation-phase therapy following acute-phase response has result ed in the need to characterize the longer-term efficacy and safety of all new medications . Previous studies using " extension " protocol s suggest that mirtazapine has sustained antidepressant effects . The current study was performed to evaluate the efficacy and safety of up to 1 year of mirtazapine therapy , using a more rigorous , r and omized , placebo-controlled discontinuation design . METHOD An intent-to-treat sample of 410 patients meeting DSM-IV criteria for moderate-to-severe recurrent or chronic major depressive episodes began 8 to 12 weeks of open-label therapy with mirtazapine ( flexibly titrated , 15 - 45 mg/day ) . Thereafter , 156 fully remitted patients ( according to Hamilton Rating Scale for Depression and Clinical Global Impressions-Improvement scores ) were r and omly assigned to receive 40 weeks of double-blind continuation-phase therapy with either mirtazapine or placebo . RESULTS Mirtazapine therapy reduced the rate of depressive relapse by more than half , with 43.8 % of patients relapsing on treatment with placebo as compared with 19.7 % of the mirtazapine-treated patients . The discontinuation rate due to adverse events was 11.8 % for active mirtazapine therapy versus 2.5 % for placebo . Although weight gain was significantly greater in the group receiving active medication during the double-blind phase ( p = .001 ) , patients taking mirtazapine gained only 1.4 kg ( 3.1 lb ) across the 40 weeks of continuation therapy , and there was no difference in the rates of weight gain as a newonset adverse event . CONCLUSION Continuation-phase therapy with mirtazapine is effective and well tolerated ABSTRACT Introduction :  Chronic breathlessness  is a common and distressing symptom of advanced disease with few effective treatments . Central nervous system mechanisms are important in respiratory sensation and control . Consequently , drugs which may modify processing and perception of afferent information in the brain may have a role . Antidepressants have been proposed ; however , current evidence is limited . Of potentially suitable antidepressants , mirtazapine is an attractive option given its tolerability profile , low cost , and wide availability , along with additional potential benefits . Areas covered : The paper provides an overview of the physiology of breathlessness , with an emphasis on central mechanisms , particularly the role of fear circuits and the associated neurotransmitters . It provides a potential rationale for how mirtazapine may improve chronic breathlessness and quality of life in patients with advanced disease . The evidence was identified by a literature search performed in PubMed through to October 2018 . Expert opinion : Currently , there is insufficient evidence to support the routine use of antidepressants for chronic breathlessness in advanced disease . Mirtazapine is a promising c and i date to pursue , with definitive r and omized controlled trials required to determine its efficacy and safety in this setting OBJECTIVE Antidepressants with different mechanisms of action might have different effects on brain functions . The aim of the study was therefore to investigate effects of 2 antidepressants on brain activation and to identify predictors for therapy response . METHOD Twenty-four untreated patients with major depressive disorder ( according to Structured Clinical Interview for DSM-IV ) were enrolled in a prospect i ve , r and omized , 4-week trial with mirtazapine and venlafaxine . Functional magnetic resonance imaging ( fMRI ) was performed at baseline and after 4 weeks in the patients and in 15 healthy controls . The primary outcome measure was fMRI blood-oxygen-level dependence ( BOLD ) activation .  The patients were recruited in 2007 and 2008 . RESULTS Comparison between patients and controls revealed that emotional face matching elicited enhanced activation in the anterior cingulate cortex ( ACC ) , dorsomedial prefrontal cortex , dorsolateral prefrontal cortex , and basal ganglia in patients . During treatment , a significant decrease of BOLD responses was seen in the hippocampus , basal ganglia , thalamus , and cerebellum of venlafaxine-treated patients , and a significant increase in BOLD responses was seen in the middle cingulate gyrus and supplementary motor area of mirtazapine-treated patients ( P < .05 , family wise error [ FWE ] cluster-level corrected ) . Larger BOLD responses in the left fusiform gyrus at baseline predicted a better response to venlafaxine , and smaller BOLD responses in the right rol and ic operculum at baseline predicted a better response to mirtazapine ( P < .05 , FWE cluster-level corrected ) . CONCLUSIONS These fMRI results indicate that antidepressants with different mechanisms of action have different effects on brain function . It therefore seems that fMRI can be used for therapy evaluation and response prediction and can facilitate the development of new pharmaceuticals To compare the efficacy and tolerability of antidepressants switch with extended-release venlafaxine ( venlafaxine-XR ) , mirtazapine , and paroxetine in Chinese patients with major depressive disorder who had 2 consecutive unsuccessful antidepressant trials . One hundred fifty adult patients with treatment-resistant depression according to their medical records and /or response to current treatments were r and omly assigned to receive fixed-dosage treatment of venlafaxine-XR 225 mg/d ( n = 50 ) , mirtazapine 45 mg/d ( n = 55 ) , or paroxetine 20 mg/d ( n = 45 ) for 8 weeks . The primary outcome was the remission rates that were defined as a score 7 or lower on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) . Secondary outcomes included the remission rate defined by the Self-Rating Depression Scale of 50 or lower and the response rate defined by a 50 % reduction or greater on the HRSD-17 total score , and the improvement of patients ' general health functions . The completion rates were 82 % for venlafaxine-XR , 81.8 % for mirtazapine , and 82.2 % for paroxetine . Only one patient in paroxetine arm discontinued the study owing to an adverse event . The remission rates based on the HRSD-17 were 42.0 % for venlafaxine-XR , 36.4 % for mirtazapine , and 46.7 % for paroxetine . There were no statistical significance s between treatment arms in remission rates . Similarly , there were also no significant differences between groups in secondary outcome measure .  Venlafaxine-XR , mirtazapine , and paroxetine were equally effective in the treatment of Chinese patients with major depressive disorder who failed at least 2 previous antidepressant treatments . Selecting any of these 3 antidepressants as a third-step antidepressant is a reasonable choice for this group of patients BACKGROUND AND OBJECTIVE Poststroke depression is one of the most frequent complications of stroke , affecting approximately 20 % to 40 % of all patients . In spite of the importance of this neuropsychiatric disorder , little attention has been given to the prevention of poststroke depression . The purpose of this study was to examine whether prophylactic treatment with the antidepressant mirtazapine in patients with acute stroke given from day 1 after the incidence prevents poststroke depression . METHOD Patients with ischemic stroke received either 30 mg mirtazapine or no antidepressant medication from day 1 after the stroke in an open , r and omized study design . Data were collected from August 2001 to December 2002 . Seventy patients were enrolled in the study and were reexamined on days 7 , 44 , 90 , 180 , 270 , and 360 using neurologic , functional , and depression rating scales . Those poststroke patients who developed depression ( DSM-IV criteria ) but had been r and omly assigned to the nontreatment group were given the antidepressant mirtazapine after the diagnosis of depression had been established . RESULTS Forty percent ( 14/35 ) of the nontreated patients and only 5.7 % ( 2/35 ) of the patients who were treated with mirtazapine developed poststroke depression . Altogether , 16 patients developed poststroke depression , 15 of whom remitted after initiation of treatment with mirtazapine . CONCLUSION Mirtazapine significantly reduced the rate of poststroke depression in patients with acute stroke . The study also demonstrated that this antidepressant was highly effective in treating poststroke depression OBJECTIVE Few controlled studies have addressed the issue of which antidepressant medications should be recommended for out patients who have not responded to multiple treatment trials . This study compared the efficacy of switching to mirtazapine to that of switching to a tricyclic antidepressant ( nortriptyline ) following two prospect i ve , consecutive , unsuccessful medication treatments for nonpsychotic major depressive disorder . METHOD Following lack of remission or an inability to tolerate an initial trial of citalopram for up to 12 weeks ( first step ) and a second trial with either monotherapy involving another antidepressant or augmentation of citalopram with bupropion or buspirone ( second step ) , adult out patients ( N=235 ) with nonpsychotic major depressive disorder were r and omly assigned to 14 weeks of treatment with mirtazapine ( up to 60 mg/day ) ( N=114 ) or nortriptyline ( up to 200 mg/day ) ( N=121 ) . The primary outcome , symptom remission , was defined a priori as a total exit score of < /=7 on the 17-item Hamilton Rating Scale for Depression . The 16-item Quick Inventory of Depressive Symptomatology-Self-Report ( QIDS-SR(16 ) ) , obtained at treatment visits , provided secondary outcomes of remission ( score < /=5 at exit ) and response ( > /=50 % reduction in score from baseline ) . RESULTS For mirtazapine , remission rates were 12.3 % and 8.0 % per the Hamilton and QIDS-SR(16 ) scores , respectively . For nortriptyline , remission rates were 19.8 % and 12.4 % , respectively . QIDS-SR(16 ) response rates were 13.4 % for mirtazapine and 16.5 % for nortriptyline . Neither response nor remission rates statistically differed by treatment , nor did these two treatments differ in tolerability or adverse events . CONCLUSIONS Switching to a third antidepressant monotherapy regimen after two consecutive unsuccessful antidepressant trials result ed in low remission rates ( < 20 % ) among patients with major depressive disorder There is a need to identify clinical ly useful biomarkers in major depressive disorder ( MDD ) . In this context the functional connectivity of the orbitofrontal cortex ( OFC ) to other areas of the affect regulation circuit is of interest . The aim of this study was to identify neural changes during antidepressant treatment and correlates associated with the treatment outcome . In an exploratory analysis it was investigated whether functional connectivity measures moderated a response to mirtazapine and venlafaxine .  Twenty-three drug-free patients with MDD were recruited from the Department of Psychiatry and Psychotherapy of the Ludwig-Maximilians University in Munich . The patients were subjected to a 4-wk r and omized clinical trial with two common antidepressants , venlafaxine or mirtazapine .  Functional connectivity of the OFC , derived from functional magnetic resonance imaging with an emotional face-matching task , was measured before and after the trial . Higher OFC connectivity with the left motor areas and the OFC regions prior to the trial characterized responders ( p<0.05 , false discovery rate ) . The treatment non-responders were characterized by higher OFC-cerebellum connectivity . The strength of response was positively correlated with functional coupling between left OFC and the cau date nuclei and thalami . Differences in longitudinal changes were detected between venlafaxine and mirtazapine treatment in the motor areas , cerebellum , cingulate gyrus and angular gyrus . These results indicate that OFC functional connectivity might be useful as a marker for therapy response to mirtazapine and venlafaxine and to reconstruct the differences in their mechanism of action BACKGROUND Some positive therapeutic effects in fibromyalgia syndrome ( FS ) were reported with both tricyclic and new antidepressant drugs as well as serotonergic agents ( 5HT2 and 5HT3 receptor blockers ) . METHODS In the present study , a novel antidepressant drug mirtazapine , 15 - 30 mg/day , has been used in 29 patients with FS in an open trial . RESULTS Twenty-six patients completed the six-week study . Ten ( 38 % ) were considered responders on account of the reduction of > or = 40 % on pain , fatigue and sleep disturbances and remission of depressive symptoms at the end of study . Eighteen patients had at least moderate depression before mirtazapine treatment and 8 patients presented mild depressive symptoms .  Reduction on main symptoms of FS after 6 weeks of mirtazapine treatment significantly correlated with the reduction in depression . However , the percentage of responders and patients with > or = 40 % reduction on main symptoms of fibromyalgia was similar in high and low depression groups . CONCLUSIONS The results obtained suggest that mirtazapine may be promising method of FS treatment . Further double-blind placebo-controlled studies are required to confirm these results Tricyclic antidepressants and more recent antidepressants are generally considered to have equivalent efficacy in the treatment of depression . After a previous report of a marked difference in the response to mirtazapine compared to imipramine , we report here an analysis of different symptom clusters . One hundred seven consecutive in- patients with major depression ( Diagnostic and Statistical Manual III-R , DSM-III-R ) and a Hamilton Rating Scale for Depression ( HRS-D ) score of 18 points or more were r and omly assigned to double-blind treatment . Two and four weeks after predefined blood levels had been obtained , the severity of depression was assessed using the HRS-D. The mean dosages used were 235 mg/day of imipramine and 77 mg/day of mirtazapine , the latter being in excess of the 15 - 45 mg/day range currently advised . Total HRS-D scores and seven symptom clusters were analyzed in the 85 patients ( 79 % ) who were not receiving any co-medication .  Imipramine was more effective against the clusters related to core symptoms of depression : " depression and guilt " , " retardation " , and " melancholia " , respectively . Mirtazapine showed a biphasic response with regard to the clusters " sleep " and " anxiety/agitation " , respectively , which consisted of a marked response after two weeks of predefined blood level , but with a waning of this effect at four weeks . Imipramine produced a more gradual response on these clusters , which was more pronounced at four weeks than with mirtazapine . Two aspects of the present study could be related to this finding : blood level control result ed in optimal treatment with imipramine but not mirtazapine , and - most importantly - the patients were not receiving any anxiolytic or hypnotic co-medication . These findings suggest that mirtazapine may have anxiolytic and sedative properties and fewer antidepressant properties than imipramine in severely depressed in- patients Major depression ( MD ) is underdiagnosed and undertreated in patients with temporal lobe epilepsy ( TLE ) . Side effects of some antidepressants , like increased risk of seizures and drug-drug interactions with anticonvulsants , contribute to undertreatment of MD in patients with TLE . We analyzed post hoc the data from 2 years of treatment of in patients with MD and TLE . Seventy-five patients received st and ard treatment with citalopram , mirtazapine , or reboxetine , respectively , at recommended dosage . Examinations were done with the Hamilton Rating Scale for Depression at admission and after 4 and 20 - 30 weeks . Plasma levels of anticonvulsants were examined at admission and discharge . Seizures were documented . The antidepressive treatment was efficacious in all antidepressant groups . No case of serious adverse event or drug interaction occurred . There was no increase in frequency or severity of seizures . At endpoint the dropout rate for mirtazapine was significantly higher than that for reboxetine or citalopram . Reboxetine showed a trend to be more efficacious than citalopram but not mirtazapine at Week 4 Major depression disorder is most commonly treated with antidepressants . However , due to their side effects clinicians seek non-pharmacologic options , and one of these is exercise . The literature on the benefits of exercise for depression is extensive . Nevertheless , two recent review s focusing on antidepressants vs. other therapies as a basis for clinical practice guidelines recommended mainly antidepressants , excluding exercise as a viable choice for treatment of depression . The aim of this perspective is to analyze the literature exploring the reasons for this discrepancy . Two categories of publications were examined : r and omized controlled trials ( RCTs ) and meta-analyses or systematic review s. Based on this re assessment , RCTs comparing exercise to antidepressants reported that exercise and antidepressants were equally effective . RCTs comparing exercise combined with antidepressants to antidepressants only reported a significant improvement in depression following exercise as an adjunctive treatment . Almost all the review s examining exercise vs. other treatments of depression , including antidepressants , support the use of exercise in the treatment of depression , at least as an adjunctive therapy . The two review s examining pharmacologic vs. non-pharmacologic therapies as a basis for clinical practice guidelines examined limited evidence on exercise vs. antidepressants . In addition , it is possible that academics and health care practitioners are skeptical of viewing exercise as medicine . Maybe , there is a reluctance to accept that changes in lifestyle as opposed to pharmacological treatment can alter biological mechanisms . Longitudinal studies are needed for assessing the effectiveness of exercise in real clinical setting s , as well as studies exploring dose-response relationship between exercise and depression We aim ed to compare the antidepressant and anxiolytic effects , tolerability and effects on quality of life of mirtazapine and citalopram in a r and omized , double-blind , multicentre , 8-week study . Patients with a Major Depressive Episode ( DSM-IV ) and a baseline score of > or = 22 on the Montgomery-Asberg Depression Rating Scale ( MADRS ) were r and omized to 8 weeks treatment with either mirtazapine  ( n = 137 , 15 - 60 mg/day ) or citalopram ( n = 133 , 20 - 60 mg/day ) . Efficacy was evaluated by the MADRS , Hamilton Anxiety Scale ( HAM-A ) , Clinical Global Impression scales ( CGI ) , the Leeds Sleep Evaluation Question naire ( LSEQ ) and Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . The efficacy analyses were performed on the Intent-To-Treat Group using the Last Observation Carried Forward method . Vital signs and laboratory variables are measured and adverse events recorded at each weekly visit . The magnitude of reduction from baseline in group mean MADRS scores was large in both groups , reaching after 8 weeks of treatment mean scores of 9.1 in the mirtazapine group and 8.9 in the citalopram group . Both treatments also result ed in a substantial improvement in anxiety symptoms , sleep disturbances and quality of life , and high percentage of responders . However , at day 14 , statistically significantly larger magnitudes of change favouring mirtazapine were present in the group mean MADRS , HAM-A and CGI-Severity of illness and Quality of life scores . A difference of 2.3 points on MADRS favouring mirtazapine is considered indicative for a clinical ly relevant superiority between two proven antidepressants . Mirtazapine treatment was also related to faster improvement of sleep , quality of sleep and improved alertness following awakening , as shown by statistically significant differences on the self-rating LSEQ at various time points . There were no differences between two treatment groups on self-rating QLSEQ . Both drugs were well tolerated , with a low number of patients in either group prematurely terminating the study due to adverse events  ( mirtazapine : 3.6 % , citalopram , 3.0 % ) . Sweating and nausea were statistically significantly more frequent in the citalopram group and increased appetite and complaints of weight increase in the mirtazapine group . There were no clinical ly relevant changes in laboratory parameters and vital sign variables with either treatment , except for clinical ly relevant increase in body weight , occurring more frequently in mirtazapine patients . In this study , mirtazapine and citalopram were equally effective in reducing symptoms of depression and anxiety , and well tolerated . However , mirtazapine was significantly more effective than citalopram after 2 weeks of treatment on the MADRS , HAM-A and CGI Severity of illness and Quality of life scales . This finding , consistently present at all major efficacy variables , suggests potentially faster onset of efficacy of mirtazapine over citalopram OBJECTIVE Current clinical knowledge holds that antidepressants have a delayed onset of efficacy . However , the delayed onset hypothesis has been question ed recently by survival analytical approaches . We aim ed to test whether early improvement under antidepressant treatment is a clinical ly useful predictor of later stable response and remission . METHOD We analyzed data from a r and omized double-blind controlled trial with  mirtazapine and paroxetine  in patients with major depression ( DSM-IV ) .  Improvement was defined as a 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) score reduction of > or = 20 % . Stable response was defined as > or = 50 % HAM-D-17 score reduction at week 4 and week 6 , and stable remission as a HAM-D-17 score of < or = 7 at week 4 and week 6 . Sensitivity , specificity , positive predictive value ( PPV ) , and negative predictive value ( NPV ) were calculated . RESULTS Improvement occurred in a majority of the analyzed patients within 2 weeks ( mirtazapine : 72.7 % of 109 patients ; paroxetine : 64.9 % of 103 patients ) . Early improvement was a highly sensitive predictor of later stable response or stable remission for both drugs . NPV approached maximum values as early as week 2 for mirtazapine and week 3 for paroxetine . After 2 weeks of treatment with mirtazapine and 3 weeks with paroxetine , almost none of the patients who had not yet improved became a stable responder or stable remitter in the later course . CONCLUSION Our results strongly suggest that early improvement predicts later stable response with high sensitivity . These empirically derived data question the delayed onset hypothesis for both antidepressants tested and provide important clinical clues for an individually tailored antidepressant treatment This study investigated the possible association of the MAOA T941 G gene variant with differential antidepressant response to  mirtazapine and /or paroxetine in 102 patients with major depression ( DSM‐IV criteria ) participating in a r and omized double‐blind controlled clinical trial . Female mirtazapine‐treated  patients homozygous for the T‐allele had a significantly faster and better treatment response than TG/GG‐ patients . In males , we failed to show an association between MAOA T941 G gene variant and mirtazapine response . In the paroxetine‐treated group , there were no significant differences in treatment response between MAOA T941 G genotype groups . Time course of response and antidepressant efficacy  of mirtazapine , but not paroxetine , seem to be influenced in a clinical ly relevant manner by this allelic variation within the MAOA gene , at least in female patients . An independent replication of our finding is needed . If replicated , genotyping of this locus could become a promising tool to predict response to mirtazapine treatment in females suffering from major depression . © 2006 Wiley‐Liss , This double-blind study compared initial combination therapy against monotherapy using two antidepressant drugs with complementary mechanisms of action on the serotonin ( 5-HT ) and norepinephrine ( NE ) systems . Sixty one adult patients with a DSM-IV diagnosis of unipolar depression were r and omized to receive mirtazapine ( 30 mg/day ) , paroxetine ( 20 mg/day ) , or the combination of both drugs for 6 weeks . Response at week 4 was defined as a 30 % reduction in the Montgomery-Asberg Depression Rating Scale ( MADRS ) , and at week 6 as a 50 % reduction in the MADRS . Remission was defined as a reduction in the MADRS score to 10 points or less . After 4 weeks , non-responders in the monotherapy groups had their medication dose increased by 50 % . After 6 weeks , non-responders on monotherapy had the second trial drug added to their current regimen . Non-responders on combination therapy had the dosage of both drugs increased by 50 % . There was a significantly greater decrease in MADRS scores in the combination group compared to the monotherapy groups at days 28 , 35 and 42 , with a 10 point difference separating the combination from the monotherapies at day 42 . Remission rates at week 6 were 19 % on mirtazapine , 26 % on paroxetine , and 43 % on the combination . Fifteen patients in the mirtazapine arm and 10 in the paroxetine arm who did not respond had the other drug added to their current regimen , and 5 on the combination had an increase in dose of both drugs secondary to non-response . Of these 30 patients , approximately 50 % went on to achieve remission in the subsequent 2 weeks . These results indicate that the combined use of two antidepressants was well tolerated and produced a greater improvement than monotherapy BACKGROUND The purpose of this study was to compare the overall effectiveness of 2 treatment strategies for in patients with severe major depressive episode ( DSM-III-R ) : ( 1 ) mirtazapine ( phase 1 ) and subsequent lithium addition ( phase 2 ) or ( 2 ) imipramine ( phase 1 ) and subsequent lithium addition ( phase 2 ) . We previously reported the results of phase 1 . METHOD In phase 1 , patients were r and omly assigned to treatment with either mirtazapine or imipramine , and doses were adjusted to obtain predefined blood drug levels . Nonresponders had lithium added to the double-blind mirtazapine or imipramine medication . The dose was adjusted to obtain a blood lithium level of 0.5 - 1.0 mmol/L. Treatment effects were evaluated weekly by the Montgomery-Asberg Depression Rating Scale for up to 2 weeks on this blood lithium level . RESULTS Data for 100 patients were available for comparison of the 2 treatment strategies . 80 patients received no comedication . By the end of phase 2 , 24 ( 48 % ) of 50 had responded to mirtazapine and 32 ( 64 % ) of 50 had responded to imipramine ( intent-to-treat analysis ) . A survival analysis of the total patient group intent-to-treat showed a significant difference in favor of the treatment strategy with imipramine and subsequent lithium addition . CONCLUSION Efficacy of imipramine and subsequent lithium addition for nonresponders is superior to the same treatment strategy with mirtazapine . This applies to the patient sample studied , which consisted of 100 severely depressed in patients , 29 of whom were psychotically depressed . More serious side effects of imipramine , however , led to discontinuation of imipramine in 5 patients . No serious side effects were observed during the phase of lithium addition to either imipramine or mirtazapine . We , therefore , prefer to start treatment with imipramine and test for fixed blood drug levels , and , if necessary , add lithium . In the case of prohibitive side effects , patients are switched to a modern antidepressant such as mirtazapine , and , if necessary , lithium is added to this antidepressant The catechol-O-methyltransferase ( COMT ) is a major degrading enzyme in the metabolic pathways of catecholaminergic neurotransmitters such as dopamine and norepinephrine . This study investigated whether the functionally relevant Val108/158Met gene variant is associated with differential antidepressant response to mirtazapine and /or paroxetine in 102 patients with major depression ( DSM-IV criteria ) participating in a r and omized clinical trial with both drugs . In patients treated with mirtazapine , but not paroxetine , allelic variations in the COMT gene were associated with differential response . COMTVAL/VAL and COMTVAL/MET genotype carriers showed a better response than COMTMET/MET-bearing patients in the mirtazapine group . Moreover , carriers of the COMTVAL/VAL or COMTVAL/MET genotype had significantly greater HAMD-17 ( Hamilton Rating Scale for Depression 17 item version ) score reductions than COMTMET/MET homozygotes from week 2 to 6 , respectively , in the mirtazapine group . Time course of response and antidepressant efficacy of mirtazapine , but not paroxetine , seem to be influenced in a clinical ly relevant manner by this allelic variation within the COMT gene AIM To explore the effects and mechanism of action of antidepressant mirtazapine in functional dyspepsia ( FD ) patients with weight loss . METHODS Sixty depressive FD patients with weight loss were r and omly divided into a mirtazapine group ( MG ) , a paroxetine group ( PG ) or a conventional therapy group ( CG ) for an 8-wk clinical trial . Adverse effects and treatment response were recorded . The Nepean Dyspepsia Index-symptom ( NDSI ) checklist and the 17-item Hamilton Rating Scale of Depression ( HAMD-17 ) were used to evaluate dyspepsia and depressive symptoms , respectively . The body composition analyzer was used to measure body weight and fat . Serum hormone levels were measured by ELISA . RESULTS ( 1 ) After 2 wk of treatment , NDSI scores were significantly lower for the MG than for the PG and CG ; ( 2 ) After 4 or 8 wk of treatment , HAMD-17 scores were significantly lower for the MG and PG than for the CG ; ( 3 ) After 8 wk of treatment , patients in the MG experienced a weight gain of 3.58 ± 1.57 kg , which was significantly higher than that observed for patients in the PG and CG . Body fat increased by 2.77 ± 0.14 kg , the body fat ratio rose by 4 % , and the visceral fat area increased by 7.56 ± 2.25 cm(2 ) ; and ( 4 ) For the MG , serum hormone levels of ghrelin , neuropeptide Y ( NPY ) , motilin ( MTL ) and gastrin ( GAS ) were significantly upregulated ; in contrast , those of leptin , 5-hydroxytryptamine ( 5-HT ) and cholecystokinin ( CCK ) were significantly downregulated . CONCLUSION Mirtazapine not only alleviates symptoms associated with dyspepsia and depression linked to FD in patients with weight loss but also significantly increases body weight ( mainly the visceral fat in body fat ) . The likely mechanism of mirtazapine action is regulation of brain-gut or gastrointestinal hormone levels OBJECTIVE Depression is common in dementia , causing considerable distress and other negative impacts . Treating it is a clinical priority , but the evidence base is sparse and equivocal . This trial aim ed to determine clinical effectiveness of sertraline and mirtazapine in reducing depression 13 weeks post r and omisation compared with placebo . DESIGN Multicentre , parallel-group , double-blind placebo-controlled r and omised controlled trial of the clinical effectiveness of sertraline and mirtazapine with 13- and 39-week follow-up . SETTING Nine English old-age psychiatry services . PARTICIPANTS A pragmatic trial . Eligibility : probable or possible Alzheimer 's disease ( AD ) , depression ( 4 + weeks ) and Cornell Scale for Depression in Dementia ( CSDD ) score of 8 + . EXCLUSIONS clinical ly too critical ( e.g. suicide risk ) ; contraindication to medication ; taking antidepressants ; in another trial ; and having no carer . INTERVENTIONS ( 1 ) Sertraline ; ( 2 ) mirtazapine ; and ( 3 ) placebo , all with normal care . Target doses : 150 mg of sertraline or 45 mg of mirtazapine daily . MAIN OUTCOME MEASURES OUTCOME CSDD score . R and omisation : Allocated 1 : 1 : 1 through Trials Unit , independently of trial team . Stratified block r and omisation by centre , with r and omly varying block sizes ; computer-generated r and omisation . Blinding : Double blind : medication and placebo identical for each antidepressant . Referring clinicians , research workers , participants and pharmacies were blind . Statisticians blind until analyses completed . RESULTS Numbers r and omised : 326 participants r and omised ( 111 placebo , 107 sertraline and 108 mirtazapine ) . OUTCOME Differences in CSDD at 13 weeks from an adjusted linear-mixed model : mean difference ( 95 % CI ) placebo-sertraline 1.17 ( -0.23 to 2.78 ; p = 0.102 ) ; placebo-mirtazapine 0.01 ( -1.37 to 1.38 ; p = 0.991 ) ; and mirtazapine-sertraline 1.16 ( -0.27 to 2.60 ; p = 0.112 ) . HARMS Placebo group had fewer adverse reactions ( 29/111 , 26 % ) than sertraline ( 46/107 , 43 % ) or mirtazapine ( 44/108 , 41 % ; p = 0.017 ) ; 39-week mortality equal , five deaths in each group . CONCLUSIONS This is a trial with negative findings but important clinical implication s. The data suggest that the antidepressants tested , given with normal care , are not clinical ly effective ( compared with placebo ) for clinical ly significant depression in AD . This implies a need to change current practice of antidepressants being the first-line treatment of depression in AD . From the data generated we formulated the following recommendations for future work . ( 1 ) The secondary analyses presented here suggest that there would be value in carrying out a placebo-controlled trial of the clinical effectiveness and cost-effectiveness of mirtazapine in the management of Behavioural and Psychological Symptoms of Dementia . ( 2 ) A conclusion from this study is that it remains both ethical and essential for trials of new medication for depression in dementia to have a placebo arm . ( 3 ) Further research is required to evaluate the impact that treatments for depression in people with dementia can have on their carers not only in terms of any impacts on their quality of life , but also the time they spend care-giving . ( 4 ) There is a need for research into alternative biological and psychological therapies for depression in dementia . These could include evaluations of new classes of antidepressants ( such as venlafaxine ) or antidementia medication ( e.g. cholinesterase inhibitors ) . ( 5 ) Research is needed to investigate the natural history of depression in dementia in the community when patients are not referred to secondary care services . ( 6 ) Further work is needed to investigate the cost modelling results in this rich data set , investigating carer burden and possible moderators to the treatment effects . ( 7 ) There is scope for re analysis of the primary outcome in terms of carer and participant CSDD results & NA ; Primary care patients with a major depressive disorder and 17‐item Hamilton Rating Scale for Depression ( 17‐HAM‐D ) score > 18 were r and omized to 24 weeks of treatment with mirtazapine  30‐45 mg/day ( n= 99 ) or paroxetine 20‐30 mg/day ( n=98 ) . Both treatments were efficacious in improving depressive symptomatology , as assessed by group mean 17‐HAM‐D scores , percentages of HAM‐D responders and remitters and Clinical Global Improvement responders . The mirtazapine group showed statistically significantly larger decreases from baseline in group mean 17‐HAM‐D scores at weeks 1 , 2 and 4 , and the difference with the paroxetine group reached the level of clinical relevance at weeks 2 and 4 . Antidepressant efficacy was maintained throughout both the acute and continuation phase of treatment . Both treatments were well tolerated . The only adverse event with a statistically significantly higher incidence in the mirtazapine group was fatigue . Statistically significantly more paroxetine‐treated patients complained of increased sweating , headache and nausea . The results demonstrate that both mirtazapine and paroxetine were efficacious and well tolerated when used for 24 weeks in depressed patients treated in primary care . An observed difference in efficacy favouring mirtazapine between weeks 1 and 4 indicates that mirtazapine patients had improved earlier compared to those on paroxetine , and corroborates similar findings in other comparisons of mirtazapine versus selective serotonin reuptake inhibitors Background : the efficacy and tolerability of the new antidepressant mirtazapine were evaluated in a multicentre , r and omized , double-blind , amitriptyline-controlled , 5 week clinical study . Method : 156 patients with a DSM-III diagnosis of major depressive episode and 21-item Hamilton Psychiatric Rating Scale for Depression ( HPRSD ) score ≥ 18 , were r and omized to treatment with either mirtazapine  20 - 60 mg/day or amitriptyline  75 - 225 mg/day . Results : mirtazapine and amitriptyline were equally effective in reducing depressive symptoms , as assessed by the 17-item HPRSD and MADRS scales . Mirtazapine was better tolerated than amitriptyline , with fewer drop-outs due to adverse events and lower incidences of adverse events both at the beginning and at the end of the trial . Conclusion : this study shows that mirtazapine is as effective as amitriptyline in treating major depression , while at the same time better tolerated BACKGROUND Major depressive disorder ( MDD ) is a common and debilitating illness in patients with cancer . However , the optimal treatment of depression in these patients remains uncertain , with limited evidence to support the use of pharmacologic therapy . We conducted a pilot study to evaluate the feasibility of an antidepressant clinical trial in the oncology population and the process of symptom-oriented selection of antidepressants ( citalopram or mirtazapine ) in patients with cancer and MDD . METHODS This was a single center , two-arm , nonr and omized , open-label , nine-week pilot study of mirtazapine or citalopram in cancer patients with MDD . The primary endpoint was the feasibility to recruit and to retain patients . Secondary outcomes included changes in Patient Health Question naire-9 ( PHQ-9 ) ( depression ) , Functional Assessment of Cancer Therapy-General ( FACT-G ) ( quality of life ) , Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-Fatigue ) ( fatigue ) , and Pittsburgh Sleep Quality Index ( PSQI ) ( sleep ) . We conducted descriptive statistics and responder analyses . RESULTS Of 21 patients , 18 ( 86 % ) successfully completed the study . An average of 2.8 subjects were enrolled per month . Mean scores on the PHQ-9 improved overall by 6.4 points ( 95 % confidence interval [ CI ] 3.6 - 9.2 ) . Additionally , mean FACT-G , FACIT-Fatigue , and PSQI scores improved in both study arms . CONCLUSION Conducting antidepressant clinical trials is challenging in the oncology population . We approached but did not meet our feasibility goals . Depression and quality of life ( QOL ) scores improved with both mirtazapine and citalopram , but evidence -based pharmacologic treatments for depression in cancer patients are needed The negative symptoms of  schizophrenia  remain a major clinical challenge . Mirtazapine is an antidepressant with antagonist properties at 5-HT2A , 5-HT3 and alpha 2 receptors as well as indirect 5-HT1a agonist effects . Many of these pharmacological actions have clinical or pre clinical evidence of efficacy in schizophrenia . This study was a 6-week r and omized placebo-controlled trial of mirtzepine or placebo add on to haloperidol 5 mg in the treatment of 30 patients with DSM-IV schizophrenia . The primary finding of the trial was a 42 % reduction in Positive and Negative Syndrome Scale ( PANSS ) negative symptom scores in the mirtazapine group compared to placebo at the end of 6 weeks ( mirtazapine 13.9 , SD 1.56 ; placebo 23.9 , SD 1.56 ; P = 0.000 , F = 20.31 , d.f . = 1 ) . The PANNS total scores , Clinical Global Impression severity and improvement scales in addition showed superiority of mirtazapine over placebo . There was no difference between the groups on the Hamilton depression scale at endpoint , suggesting that the improvement in negative symptoms was not an artifact of mood improvement . These results suggest a potential role for mirtazapine in the negative symptoms of schizophrenia BACKGROUND Sexual side effects are a common and bothersome reaction to selective serotonin reuptake inhibitors ( SSRIs ) , frequently leading to cessation of treatment . Mirtazapine , an alpha2-adrenoceptor and serotonin-2/3 receptor antagonist , appears to cause few sexual problems . METHOD Nineteen patients ( 12 women and 7 men ) , with SSRI-induced sexual dysfunction who were in remission from major depressive disorder ( total Hamilton Rating Scale for Depression [ HAM-D ] score < or = 10 ) , were switched to open-label mirtazapine for up to 6 weeks . Mirtazapine was titrated from 7.5 mg to 45 mg daily , as tolerated . Sexual functioning was measured weekly with the Arizona Sexual Experiences Scale ( ASEX ) , and depression was measured weekly with the HAM-D. RESULTS Eleven patients ( 58 % ) had a return of normal sexual functioning ( mean + /- SD ASEX score = 12+/-3 ) , and another 2 ( 11 % ) reported significant improvement in sexual functioning ( mean ASEX score reduced from 24+/-1 to 20+/-0 ) . All nineteen patients maintained their antidepressant response ( HAM-D score after 6 weeks of mirtazapine = 6+/-3 ) . The most commonly reported side effects ( using moderate/severe rating on a symptom checklist ) were initial sedation ( N = 3 ) , irritability ( N = 6 ) , and muscle soreness and stiffness ( N = 3 ) . Weight gain of 10 to 20 lb ( 4.5 - 9 kg ) was seen in 3 patients ( 2 women and 1 man ) . CONCLUSION Mirtazapine is an effective antidepressant for many patients experiencing SSRI-induced sexual dysfunction No studies have compared mirtazapine with duloxetine in patients with major depressive disorder ( MDD ) . Fifty-six patients were nonr and omly assigned to a 4-week treatment with either 15 to 45 mg/day of mirtazapine ( n = 22 ) or 20 to 60 mg/day of duloxetine ( n = 34 ) . The primary efficacy measurements were the Hamilton Rating Scale for Depression ( HRSD ) and the Montgomery – Åsberg Depression 6-point Rating Scale ( MADRS ) scores . The second efficacy measurements were the response and remission rates of treatment . Tolerability assessment s were also performed . Fifty-six patients ( 43 male ; age , 43.6 years ) were recruited . There was no significant difference in the discontinuation rate between the mirtazapine and duloxetine treatment groups ( P = 0.867 ) . Both mirtazapine and duloxetine significantly improved the HRSD and MADRS scores from baseline ( P < 0.0001–0.0004 ) . While mirtazapine was superior to duloxetine in the reduction of HRSD scores ( P = 0.0421 ) , there was no significant change in MADRS scores in terms of between-group differences ( P = 0.171 ) . While more somnolence was observed with mirtazapine ( P = 0.0399 ) , more nausea was associated with duloxetine ( P = 0.0089 ) . No serious adverse events were observed for either antidepressant . Mirtazapine and duloxetine were safe and well-tolerated treatments for Japanese patients with MDD . Double-blind controlled studies are needed to further explore the efficacy and safety of mirtazapine and duloxetine in Japanese patients with MDD Background A number of studies have suggested a link between the patient 's psyche and the course of inflammatory bowel disease ( IBD ) . Although pharmacotherapy with antidepressants has not been widely explored , some investigators have proposed that treating psychological co-morbidities with antidepressants may help to control disease activity . To date a systematic analysis of the available studies assessing the efficacy of antidepressants for the control of somatic symptoms in IBD patients has not been performed . Methods We search ed electronic data bases , without any language restriction . All relevant papers issued after 1990 were examined . Results 12 relevant publications were identified . All of them referred to non-r and omised studies . Antidepressants reported in these publications included paroxetine , bupropion , amitriptyline , phenelzine , and mirtazapine . In 10 articles , paroxetine , bupropion , and phenelzine were suggested to be effective for treating both psychological and somatic symptoms in patients suffering from IBD . Amitriptyline was found ineffective for treating somatic symptoms of IBD . Mirtazapine was not recommended for IBD patients . Conclusion Although most of review ed papers suggest a beneficial effect of treatment with antidepressants in patients with IBD , due to the lack of reliable data , it is impossible to judge the efficacy of antidepressants in IBD . Properly design ed trials are justified and needed based upon the available uncontrolled data INTRODUCTION Depression , stress and antidepressant treatment have been found to modulate the expression of brain-derived neurotrophic factor ( BDNF ) . Recent research suggests that serum BDNF concentration is reduced in depression and that antidepressant treatment leads to an increase in serum BDNF concentration . METHODS We studied depressed patients receiving a r and omized antidepressant treatment with either mirtazapine ( n=29 ) or venlafaxine ( n=27 ) for 28 days in a prospect i ve design . Changes in the concentrations of serum neurotrophins in response to antidepressant treatment were assessed . RESULTS There was a significant " treatment " by " medication " interaction effect on BDNF serum concentrations that indicated a decline of BDNF in venlafaxine-treated patients ( 7.82±3.75 - 7.18±5.64 ng/mL ) , while there was an increase in mirtazapine-treated patients ( 7.64±6.23 - 8.50±5.37 ng/mL ) . There was a trend for a " treatment " by " remission " interaction with a favourable clinical course being related to increasing serum BDNF . DISCUSSION Changes in BDNF serum concentrations as a result of antidepressant therapy depend on the antidepressant and potentially on the clinical course BACKGROUND Antidepressants , especially selective serotonin reuptake inhibitors ( SSRIs ) , venlafaxine , and clomipramine , are frequently associated with sexual dysfunction . Other antidepressants ( nefazodone , mirtazapine , bupropion , amineptine , and moclobemide ) with different mechanisms of action seem to have fewer sexual side effects . The incidence of sexual dysfunction is underestimated , and the use of a specific question naire is needed . METHOD The authors analyzed the incidence of antidepressant-related sexual dysfunction in a multicenter , prospect i ve , open-label study carried out by the Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction . The group collected data from April 1995 to February 2000 on patients with previously normal sexual function who were being treated with antidepressants alone or antidepressants plus benzodiazepines . One thous and twenty-two out patients ( 610 women , 412 men ; mean age = 39.8 + /- 11.3 years ) were interviewed using the Psychotropic-Related Sexual Dysfunction Question naire , which includes questions about libido , orgasm , ejaculation , erectile function , and general sexual satisfaction . RESULTS The overall incidence of sexual dysfunction was 59.1 % ( 604/1022 ) when all antidepressants were considered as a whole . There were relevant differences when the incidence of any type of sexual dysfunction was compared among different drugs : fluoxetine , 57.7 % ( 161/279 ) ; sertraline , 62.9 % ( 100/159 ) ; fluvoxamine , 62.3 % ( 48/77 ) ; paroxetine , 70.7 % ( 147/208 ) ; citalopram , 72.7 % ( 48/66 ) ; venlafaxine , 67.3 % ( 37/55 ) ; mirtazapine , 24.4 % ( 12/49 ) ; nefazodone , 8 % ( 4/50 ) ; amineptine , 6.9 % ( 2/29 ) ; and moclobemide , 3.9 % ( 1/26 ) . Men had a higher frequency of sexual dysfunction ( 62.4 % ) than women ( 56.9 % ) , although women had higher severity . About 40 % of patients showed low tolerance of their sexual dysfunction . CONCLUSION The incidence of sexual dysfunction with SSRIs and venlafaxine is high , ranging from 58 % to 73 % , as compared with serotonin-2 ( 5-HT2 ) blockers ( nefazodone and mirtazapine ) , moclobemide , and amineptine Abstract Background : Depression is quite common among cancer patients . It has yet to be determined which antidepressant is the most effective in cancer patients with depression . Methods : The present study included 21 consecutive depressed oncology patients of whom 19 were followed up for 6 months . All patients initially received mirtazapine 15 mg/day and the dose was increased in the absence of significant treatment response and adverse effects . Results : Depressive symptoms diminished at the end of month 1 and this improvement was maintained for the remaining 23 weeks of the study . Mean 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) scores fell significantly from 21.4 ± 4.9 at baseline to 6.5 ± 3.2 at the end of the first month of treatment ( p < 0.001 ) . Among the 19 patients who were followed up , five reported at least one adverse effect during treatment ; however , the vast majority of these adverse effects were described as mild to moderate . Conclusion : This prospect i ve , open-label study provides preliminary evidence regarding the efficacy , safety and tolerability  of mirtazapine treatment in cancer patients with depression . Relatively low doses of mirtazapine appeared to be safe and effective for treating cancer patients undergoing radiotherapy and /or chemotherapy , and the reduction in the severity of depressive symptoms was maintained until the end of the 24-week treatment period OBJECTIVE Psychomotor disturbances can frequently be found in depressed patients and may have an important influence on the ability to drive . Additionally , effects of sedation , as seen with some antidepressants , probably impair driving performance . The present study was design ed to evaluate the effects of antidepressant monotherapy on psychomotor functions related to car-driving skills in depressive patients in a routine clinical setting . METHOD In patients ( N = 100 ) who met the ICD-10 and DSM-IV criteria for major depressive disorder were tested under steady-state plasma level conditions prior to being discharged to out-patient treatment . The study ran from January 2004 through March 2005 . All patients participated voluntarily and gave informed consent . According to the German guidelines for road and traffic safety , data were collected with the computerized Act & React Testsystem ART-90 and the Wiener Testsystem , measuring visual perception , reaction time , selective attention , vigilance , and stress tolerance . Psychopathologic symptoms were rated with the Hamilton Rating Scale for Depression . RESULTS Before discharge to outpatient treatment , 24 % of the patients tested were without clinical ly relevant psychomotor disturbances . In 60 % of the cases , mild to moderate impairments could be seen , and about 16 % of the patients were considered as severely impaired in psychomotor functions related to car-driving abilities . Data show that patients treated with selective serotonin reuptake inhibitors ( SSRIs ) or the noradrenergic and specific serotonergic antidepressant ( NaSSA ) mirtazapine had an altogether better test performance in comparison with patients receiving tricyclic antidepressants ( TCAs ) . Differences were most pronounced in measures of reactivity , stress tolerance , and selective attention . Statistically significant differences between patients treated with TCAs or the serotonin-norepinephrine reuptake inhibitor ( SNRI ) venlafaxine could not be found . Among the newer antidepressants there is an advantage for patients treated with mirtazapine , especially in tasks with high multi-channel perception and output dem and s. CONCLUSION About 16 % of depressive patients discharged from hospital to outpatient treatment must be considered unfit to drive . In 60 % of the cases , patients performed at a question able level of fitness for driving , and it seems justified to counsel patients individually , taking into account compensational factors . Data point to an advantage for patients treated with SSRIs or mirtazapine when compared with TCAs or venlafaxine . However , causal relationships can not be drawn from our data Depression is common in schizophrenia and worsens its course . The role of antidepressants for schizophrenic depression remains unclear . In this study , the efficacy of add-on mirtazapine on depression in schizophrenia was explored in a subsidiary arm of a recent r and omized controlled trial . Patients ( n = 41 ) with chronic but stable schizophrenia and inadequate response to stable doses of different first-generation antipsychotics  were treated with add-on mirtazapine 30 mg or placebo during a 6-week double-blind phase and with open-label add-on mirtazapine during a 6-week extension phase . Efficacy measures were the Calgary Depression Scale for Schizophrenia ( CDSS ) and the Positive and Negative Syndrome Scale depression item . During the double-blind phase , both measures ' scores decreased significantly in the mirtazapine group but not in the placebo group ( for the CDSS , 52.0 % vs 19.6 % , respectively ) . During the open‐label phase , both groups demonstrated significant improvements . In between‐group comparison , a trend favoring mirtazapine did not reach statistical significance . The changes in the CDSS correlated positively with those in the Positive and Negative Syndrome Scale negative , positive and total (sub)scales  for mirtazapine‐treated patients during the double‐blind phase . Depressed patients with schizophrenia may benefit from mirtazapine – first‐generation antipsychotics combination , with no increased risk for psychosis . However , more studies are needed BACKGROUND Sexual dysfunction commonly occurs during  antidepressant treatment .  However , the reported rates of sexual dysfunction vary across antidepressants and are typically underreported in product literature . The objectives of this study were ( 1 ) to estimate the prevalence of  sexual dysfunction among patients taking newer antidepressants ( bupropion immediate release [ IR ] , bupropion sustained release [ SR ] , citalopram , fluoxetine , mirtazapine , nefazodone , paroxetine , sertraline , venlafaxine , and venlafaxine extended release [ XR ] )  and ( 2 ) to compare physician-perceived with patient-reported prevalence rates of antidepressant-associated sexual dysfunction . METHOD This cross-sectional , observational study was conducted in 1101 U.S. primary care clinics . Adult out patients ( 4534 women and 1763 men ) receiving antidepressant monotherapy were enrolled . The prevalence of sexual dysfunction was measured using the Changes in Sexual Functioning Question naire . RESULTS In the overall population , bupropion IR ( 22 % ) and SR ( 25 % ) and nefazodone ( 28 % ) were associated with the lowest risk for sexual dysfunction , whereas selective serotonin reuptake inhibitor ( SSRI ) antidepressants , mirtazapine , and venlafaxine XR were associated with higher rates ( 36%-43 % ) . In a prospect ively defined sub population unlikely to have predisposing factors for sexual dysfunction , the prevalence of sexual dysfunction ranged from 7 % to 30 % , with the odds of having sexual dysfunction 4 to 6 times greater with SSRIs or venlafaxine XR than with bupropion SR . Physicians consistently underestimated the prevalence of antidepressant-associated sexual dysfunction . CONCLUSION Ours is the first study to assess sexual dysfunction across the newer antidepressants using consistent methodology and a vali date d rating scale . Overall , SSRIs and venlafaxine XR were associated with higher rates of sexual dysfunction than bupropion or nefazodone . Because antidepressant-associated sexual dysfunction is considerably underestimated by physicians , greater recognition and education are imperative when prescribing antidepressant treatment Mirtazapine is an antidepressant whose side effect profile differs from that of first-line agents ( selective serotonin reuptake inhibitors ) used in the treatment of panic disorder . The present study compared the effect of mirtazapine and fluoxetine in the treatment of panic disorder in a double-blind , r and omized , flexible-dose trial conducted with out patients . After a 1-week single-blind placebo run-in , 27 patients entered an 8-week double-blind phase in which they were r and omly assigned to treatment with either mirtazapine or fluoxetine . Both groups improved significantly in all but one efficacy measure ( P < or = 0.01 ) . ANOVA showed no significant differences between the two treatment groups in number of panic attacks , Hamilton Anxiety Scale or Sheehan Phobic Scale , whereas measures of patient global evaluation of phobic anxiety were significantly different between groups ( F1,20 = 6.91 , P = 0.016 ) favoring mirtazapine . For the 22 patients who completed the study , the mean daily dose of mirtazapine was 18.3 + /- 1.3 vs 14.0 + /- 1.0 mg for fluoxetine at the endpoint . Weight gain occurred more frequently in the mirtazapine group ( 50 vs 7.7 % , P = 0.04 ) and nausea and paresthesia occurred more often in the fluoxetine group ( P = 0.01 ) . Results suggest that mirtazapine has properties that make it attractive for the treatment of panic disorder STAR*D is a multisite , prospect i ve , r and omized , multistep clinical trial of out patients with nonpsychotic major depressive disorder . The study compares various treatment options for those who do not attain a satisfactory response with citalopram , a selective serotonin reuptake inhibitor antidepressant . The study enrolls 4000 adults ( ages 18 - 75 ) from both primary and specialty care practice s who have not had either a prior inadequate response or clear-cut intolerance to a robust trial of protocol treatments during the current major depressive episode . After receiving citalopram ( level 1 ) , participants without sufficient symptomatic benefit are eligible for r and omization to level 2 treatments , which entail four switch options ( sertraline , bupropion , venlafaxine , cognitive therapy ) and three citalopram augment options ( bupropion , buspirone , cognitive therapy ) . Those who receive cognitive therapy ( switch or augment options ) at level 2 without sufficient improvement are eligible for r and omization to one of two level 2A switch options ( venlafaxine or bupropion ) . Level 2 and 2A participants are eligible for r and om assignment to two switch options ( mirtazapine or nortriptyline ) and to two augment options ( lithium or thyroid hormone ) added to the primary antidepressant ( citalopram , bupropion , sertraline , or venlafaxine ) ( level 3 ) . Those without sufficient improvement at level 3 are eligible for level 4 r and om assignment to one of two switch options ( tranylcypromine or the combination of mirtazapine and venlafaxine ) . The primary outcome is the clinician-rated , 17-item Hamilton Rating Scale for Depression , administered at entry and exit from each treatment level through telephone interviews by assessors masked to treatment assignments . Secondary outcomes include self-reported depressive symptoms , physical and mental function , side-effect burden , client satisfaction , and health care utilization and cost . Participants with an adequate symptomatic response may enter the 12-month naturalistic follow-up phase with brief monthly and more complete quarterly assessment An open-label , non-r and omized , pilot study has been performed in in patients in need of treatment with an antipsychotic ( risperidone ) and an antidepressant ( mirtazapine )  with the objective to preliminarily assess a possible pharmacokinetic interaction and the tolerability of this combination . A 1 - 4-week single drug treatment phase ( risperidone 1 - 3 mg bid or mirtazapine 30 mg nocte ) was followed by a 2 - 4-week combined drug treatment phase at unchanged doses . Twelve patients were enrolled , nine of whom were treated with risperidone  in the single drug phase . Results of plasma level measurements are available for six patients and indicate that adding mirtazapine to risperidone does not alter steady-state plasma concentrations of risperidone and its 9-hydroxy metabolite . Data from one patient suggest that adding risperidone to mirtazapine does not result in clinical ly relevant changes in plasma concentrations of either compound . The combination was well tolerated and no major or relevant adverse events were observed . Adding risperidone to mirtazapine probably does not necessitate a change of the dosage of either drug , but more extensive investigations are needed Brain-derived neurotrophic factor ( BDNF ) is a c and i date molecule for influencing the clinical response to antidepressant treatment . The aims of this study were to determine the relationship between the Val66Met polymorphism in the BDNF gene and the response to  mirtazapine in 243 Korean subjects with major depressive disorder ( MDD ) . The reduction in the Hamilton Depression score over the 8-week treatment period was not influenced by BDNF V66 M genotypes . A marginal effect of genotype on somatic anxiety score was observed at baseline ( P = 0.047 in the dominant model ) . However , genotype – time interaction had no effect on somatic anxiety score after the 8-week a treatment period . Plasma BDNF levels tended to increase during mirtazapine treatment , although without statistical significance ( P = 0.055 ) . After 8 weeks of mirtazapine  treatment , plasma BDNF levels were higher in Met allele homozygotes ( 1499.7 ± 370.6 ng/mL ) than in Val allele carriers ( 649.7 ± 158.5 ng/mL , P = 0.049 ) . Our results do not support the hypothesis that the Val66Met promoter polymorphism in the BDNF gene influences the therapeutic response  to mirtazapine in Korean MDD patients . However , our data indicate that this polymorphism results in increased plasma BDNF  after mirtazapine treatment Antidepressant effects of mirtazapine and imipramine were compared in a r and omized , double blind , fixed blood-level study with in- patients in a single centre . Patients with a DSM-III-R diagnosis of major depression and a Hamilton ( 17-item ) score of ≥18 were selected . After a drug-free and a placebowashout period of 7 days in total , 107 patients still fulfilling the HRSD criterion of ≥18 , started on active treatment . The dose was adjusted to a predefined fixed blood level to avoid suboptimal dosing of imipramine . Concomitant psychotropic medication was administered only in a few cases because of intolerable anxiety or intolerable psychotic symptoms . Eight patients dropped out and two were excluded from analyses because of non-compliance ; 97 completed the study . According to the main response criterion ( 50 % or more reduction on the HRSD score ) 11/51 ( 21.6 % ) patients responded on mirtazapine and 23/46 ( 50 % ) on imipramine after 4 weeks ' treatment on the predefined blood level . Such a dramatic difference in efficacy between antidepressants has not often been reported before . The selection of ( severely ill ) in- patients , including those with suicidal or psychotic features , may have significance in this respect . Optimization of treatment with the reference drug imipramine through blood level control , exclusion of non-compliance for both drugs , exclusion of most concomitant medication and a low drop-out rate may also have contributed . It is concluded that imipramine is superior to mirtazapine in the patient population studied OBJECTIVE To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed in patients and out patients . METHOD Patients with a major depressive episode ( DSM-III-R ) , a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression ( HAM-D ) , and > or=2 on HAM-D Item 1 ( depressed mood ) were r and omly assigned to a 6-week treatment with either mirtazapine ( N=66 , 15 - 60 mg/day ) or fluoxetine ( N=67 , 20 - 40 mg/day ) . The upper limit of the mirtazapine dose range was above the dose range approved in the United States ( 15 - 45 mg/day ) . Efficacy was evaluated by the HAM-D , Clinical Global Impressions , the Visual Analogue Mood Rating Scale ( VAMRS ) , and the Quality of Life Enjoyment and Satisfaction Question naire ( QLESQ ) . The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method . RESULTS Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group . The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period , reaching statistical significance at days 21 and 28 . At assessment s from day 21 and onward , the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points , the magnitude of difference usually seen between an efficacious antidepressant drug and placebo . Mean dosages at weeks 1 - 4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine ; the respective dosages at weeks 5 - 6 were 56.3 mg and 35.8 mg . Similar numbers of patients dropped out due to adverse events ; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group . CONCLUSION We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy BACKGROUND Sleep complaints are common in patients with major depressive disorder ( MDD ) . Both MDD and antidepressant drugs characteristically alter objective sleep measures . This study compares the effects of mirtazapine and fluoxetine on sleep continuity measures in DSM-IV MDD patients with insomnia . METHOD Patients ( N = 19 ) received initial baseline polysomnography evaluations over 2 consecutive nights . Subjects were r and omly assigned to either fluoxetine ( 20 - 40 mg/day ) or mirtazapine ( 15 - 45 mg/day ) treatment for an 8-week , double-blind , double-dummy treatment trial . Single-night polysomnograms were conducted at weeks 1 , 2 , and 8 , with depression ratings assessed at baseline and weeks 1 , 2 , 3 , 4 , 6 , and 8 . Statistical analysis was performed by repeated- measures analysis of variance followed by Dunnet 's post hoc analyses . RESULTS Patients receiving mirtazapine ( N = 8) had significant improvement in objective sleep physiology measures at 8 weeks . Improvements in sleep latency , sleep efficiency , and wake after sleep onset were significant after only 2 weeks of mirtazapine treatment . No significant changes in sleep continuity measures were observed in the fluoxetine group ( N = 11 ) . Both groups improved clinical ly in mood and subjective sleep measures from baseline , with no differences between groups . CONCLUSION These data demonstrate the differential effects of mirtazapine and fluoxetine , with significant improvement in favor of mirtazapine , on objective sleep parameters in MDD patients with insomnia Background . Non-adherence to antidepressant treatment is not routinely measured in practical clinical trials . It has not been related to outcomes in a large sample of adults with chronic and /or recurrent major depressive disorder ( MDD ) or any sample treated with antidepressant combinations . Methods . Adult out patients with chronic and /or recurrent MDD were r and omized to 12 weeks of treatment with bupropion-SR plus escitalopram , venlafaxine – XR plus mirtazapine , or escitalopram plus placebo . We compared non-adherence ( the frequency with which daily medications were not taken ) and specifically the frequency of temporarily stopping and /or skipping medication , or reducing or increasing the dose across treatments in 567 participants using a self-report question naire collected at each visit . We tested the association between non-adherence , and both treatment type and outcomes . Results . A non-adherence rate under 10 % was reported by 77.9 % , 70.9 % , and 71.6 % of participants during weeks 1–4 , 5–12 , and 1–12 , respectively . Antidepressant combinations were associated with a higher non-adherence rate than monotherapy during weeks 1–4 and 1–12 . During weeks 1–4 , 24.1 % stopped/skipped doses and 6.1 % reduced the dose . During weeks 5–12 , 34.7 % stopped/skipped doses and 9.4 % reduced the dose . Across 12 weeks , 43.2 % stopped/skipped doses , and 12.9 % reduced the dose . Stopping/skipping doses during all time frames and dose decreases during weeks 1–12 occurred most frequently with combination treatments . Non-adherence was unrelated to symptom remission , response , or symptom change . Conclusions . With closely monitored treatment , non-adherence is low and unrelated to depressive symptom outcome . Nonadherence is highest with antidepressant combinations . Specific non-adherent events are most often sporadic . ( Journal of Psychiatric Practice 2014;20:118–132 Our objective was to determine if pretreatment anxiety levels were associated with preferential response to bupropion sustained release ( n = 122 ) or sertraline ( n = 126 ) during a 16-week r and omized acute phase treatment study . Both agents had comparable antidepressant activity , and comparable anxiolytic effects using the intent-to-treat sample . Baseline anxiety levels were not related to antidepressant efficacy , and they did not differentiate responders to each agent . Time to clinical ly significant anxiolysis did not differentiate between treatment groups or between responders to each agent . These results contradict the commonly held , but unsubstantiated , belief that in clinical ly depressed anxious patients , serotonergic antidepressants are especially anxiolytic and that such patients preferentially benefit from the antidepressant or anxiolytic effects of selective serotonin reuptake inhibitors . Thus , the clinical decision to select between these two agents when treating depressed out patients can not rest on either levels of pretreatment anxiety or on anticipation of more rapid or more complete anxiolysis Background : The tricyclic antidepressant amitriptyline is the only drug with prophylactic efficacy for chronic tension-type headache .  However , amitriptyline is only moderately effective , with headache reduction of approximately 30 % , and treatment is often hampered by side effects . Mirtazapine is a relatively new so-called noradrenergic and specific serotonergic antidepressant , which is more specific and therefore generally better tolerated . Objective : To evaluate the efficacy of mirtazapine . Methods : Twenty-four nondepressed patients with chronic tension-type headache were included in a r and omized , double-blind , placebo-controlled , crossover trial . All patients had tried numerous other treatments .  Mirtazapine 15 to 30 mg/day or placebo was each given for 8 weeks separated by a 2-week wash-out period . Results : Twenty-two patients completed the study . The primary efficacy variable , area-under-the-headache curve ( AUC ; duration × intensity ) , was lower during treatment with mirtazapine ( 843 ) than during treatment with placebo ( 1,275 ) ( p = 0.01 ) . Mirtazapine also reduced the secondary efficacy variables headache frequency ( p = 0.005 ) , headache duration ( p = 0.03 ) , and headache intensity ( p = 0.03 ) and was well tolerated . Conclusions : Mirtazapine  reduced AUC by 34 % more than placebo in difficult-to-treat patients . This finding is clinical ly relevant and may stimulate the development of prophylactic treatments with increased efficacy and fewer side effects for tension-type headache and other types of chronic pain Of 580 patients r and omly assigned to short-term , double-blind treatment with either mirtazapine , amitriptyline or placebo , a total of 217 patients clinical ly judged to be responders subsequently continued on the same medication for up to 2 years in the long-term treatment study  ( mirtazapine , n = 74 ; amitriptyline , n = 86 and placebo , n = 57 ) . The efficacy of mirtazapine in relapse prevention was seen in an analysis of the first 20 weeks data . Significantly fewer patients relapsed during treatment with mirtazapine compared with placebo ( p < 0.05 ) , and a significantly longer time to relapse was shown on the survival analysis . There was a significant advantage for amitriptyline compared with placebo in the first 20 weeks , with fewer patients relapsing . There was a significant advantage for mirtazapine compared with amitriptyline at 20 weeks seen on the survival analysis ( p < 0.05 ) . The significant advantage for mirtazapine compared with placebo was also seen in the prophylactic phase of treatment after 20 weeks . At the endpoint there were significantly more patients in the placebo group with a return of symptoms and significantly fewer showing sustained response , Amitriptyline was better than placebo with fewer patients suffering a recurrence of symptoms , but there was no difference from placebo in the proportion of patients with sustained response .  Mirtazapine was well tolerated with a side-effect profile similar to that of placebo . The only adverse event reported significantly more frequently on mirtazapine than on placebo was weight gain . Objective ly measured weight gain was more frequent with amitriptyline ( 22 % of patients ) compared with mirtazapine ( 13 % of patients ) . Amitriptyline was associated with significantly more adverse events than either mirtazapine or placebo , in particular sedative and anticholinergic side effects . The efficacy of mirtazapine in reducing the risk of relapse and the recurrence of depression , which on some measures showed an advantage compared with amitriptyline , coupled with its improved side-effect profile , commends this antidepressant for the long-term treatment of depression OBJECTIVE The purpose of this study was to compare the effectiveness and tolerability of tranylcypromine and combination treatment with extended-release venlafaxine and mirtazapine in patients with treatment-resistant major depression whose current depressive episode had not responded adequately to treatment in three prior prospect i ve medication trials . METHOD Adult out patients with nonpsychotic major depressive disorder who had not achieved remission or had withdrawn from treatment because of intolerance in three previous prospect i ve medication trials were r and omly assigned to receive open-label treatment with either tranylcypromine ( N=58 ) or extended-release venlafaxine plus mirtazapine ( N=51 ) . The primary outcome measure was whether patients achieved remission , which was defined as a score < or = 7 at exit on the 17-item Hamilton Depression Rating Scale ( HAM-D ) . The HAM-D was administered by telephone by raters to whom treatment was masked . RESULTS Remission rates were not significantly different between the two treatment groups ( 6.9 % for the tranylcypromine group and 13.7 % for the venlafaxine plus mirtazapine group ) . The mean daily dose at exit for tranylcypromine was 36.9 mg ( SD=18.5 ) ; for venlafaxine , 210.3 mg ( SD=95.2 ) ; and for mirtazapine , 35.7 mg ( SD=17.6 ) . Tranylcypromine was associated with significantly less symptom reduction and greater attrition due to intolerance . CONCLUSIONS Remission rates were modest for both the tranylcypromine group and the extended-release venlafaxine plus mirtazapine group , and the rates were not statistically different between groups . The lower side effect burden , lack of dietary restrictions , and ease of use of venlafaxine and mirtazapine suggest that this combination may be preferred over tranylcypromine for patients with highly treatment-resistant depression who have not benefited adequately from several prior treatments OBJECTIVE The authors sought to identify genetic markers for antidepressant medication intolerance . Genetic variation in drug metabolizing enzymes such as cytochrome P450 2D6 ( CYP2D6 ) has been postulated to underlie antidepressant intolerance ( pharmacokinetic effect ) . However , variation in genes encoding serotonin receptors could also explain antidepressant side effects ( pharmacodynamic effect ) . METHOD An 8-week , double-blind , r and omized pharmacogenetic study compared the widely prescribed antidepressants paroxetine ( a selective serotonin reuptake inhibitor [ SSRI ] ) and mirtazapine ( not an SSRI ) in 246 elderly patients with major depression . Genotypes were determined for the 102 T/C single nucleotide polymorphism ( SNP ) in the serotonin 2A ( 5-HT(2A ) ) locus ( HTR2A ) , previously associated with psychotropic medication treatment outcome . Oligonucleotide microarrays were used to extensively characterize variation in the CYP2D6 gene . Clinical outcomes included treatment discontinuations , adverse events , medication compliance , and change in mood . RESULTS Survival analysis showed discontinuations due to paroxetine-induced side effects were strongly associated with the HTR2A C/C genotype . There was a significant linear relationship between the number of C alleles and the probability of discontinuation . Side effect severity in paroxetine-treated patients with the C/C genotype was also greater . In contrast , HTR2A 102 T/C genotype had no effect on mirtazapine side effects . CYP2D6 genotype did not predict treatment outcome for either medication . CONCLUSIONS Pharmacodynamic differences among patients due to variant 5-HT(2A ) receptors appear to be more important than pharmacokinetic variation in determining paroxetine intolerance . Pharmacogenetic markers may be useful in predicting antidepressant treatment outcome BACKGROUND In 2001 , the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments ( CANMAT ) partnered to produce evidence -based clinical guidelines for the treatment of depressive disorders .  A revision of these guidelines was undertaken by CANMAT in 2008 - 2009 to reflect advances in the field . This article , one of five in the series , review s new studies of psychotherapy in the acute and maintenance phase of MDD , including computer-based and telephone-delivered psychotherapy . METHODS The CANMAT guidelines are based on a question -answer format to enhance accessibility to clinicians . Evidence -based responses are based on up date d systematic review s of the literature and recommendations are grade d according to the Level of Evidence , using pre-defined criteria . Lines of Treatment are identified based on criteria that included evidence and expert clinical support . RESULTS Cognitive-Behavioural Therapy ( CBT ) and Interpersonal Therapy ( IPT ) continue to have the most evidence for efficacy , both in acute and maintenance phases of MDD , and have been studied in combination with antidepressants . CBT is well studied in conjunction with computer-delivered methods and bibliotherapy . Behavioural Activation and Cognitive-Behavioural Analysis System of Psychotherapy have significant evidence , but need replication . Newer psychotherapies including Acceptance and Commitment Therapy , Motivational Interviewing , and Mindfulness-Based Cognitive Therapy do not yet have significant evidence as acute treatments ; nor does psychodynamic therapy . LIMITATIONS Although many forms of psychotherapy have been studied , relatively few types have been evaluated for MDD in r and omized controlled trials . Evidence about the combination of different types of psychotherapy and antidepressant medication is also limited despite widespread use of these therapies concomitantly . CONCLUSIONS CBT and IPT are the only first-line treatment recommendations for acute MDD and remain highly recommended for maintenance . Both computer-based and telephone-delivered psychotherapy -- primarily studied with CBT and IPT -- are useful second-line recommendations . Where feasible , combined antidepressant and CBT or IPT are recommended as first-line treatments for acute MDD Finding predictors of the response to antidepressant therapy  is a major goal of molecular psychiatry . The genes encoding the serotonin ( SERT ) and dopamine ( DAT1 ) transporters are among the possible c and i date genes modulating an individual 's antidepressant response . In a naturalistic prospect i ve cohort study with a total of 190 fully assessed patients , improvement of depression symptoms during the 3 weeks following initiation of antidepressant therapy was recorded using the 21-item Hamilton Depression Rating Scale ( HDRS ) . The SLC6A3 3′ UTR 40-bp variable number of t and em repeats ( VNTR ) and the SLC6A4 5′ 44-bp insertion/deletion polymorphism were analyzed by polymerase chain reaction . There was a significantly smaller number of rapid responders among homozygous carriers of the DAT1 9-repeat allele ( 9/9 ) than among heterozygous ( 9/10 ) and homozygous ( 10/10 ) carriers of the 10-repeat allele ( 19 versus 37 versus 52 % , respectively , P=0.0037 ) . Median decline in HDRS score was 35 , 40 , and 52 % in patients with the 9/9 , 9/10 , and 10/10 genotypes , respectively ( P=0.013 ) . The effect was found in all classes of medications ( selective serotonin reuptake inhibitors ( SSRIs ) , tricyclics , mirtazapine , venlafaxine ) and statistically significant also within the subgroup of patients having received SSRIs . The serotonin promoter insertion/deletion genotype had no effect in the entire study group , but there was an insignificant trend of better response in the l/l and l/s carriers who received SSRIs or mirtazapine . In conclusion , the dopamine transporter VNTR polymorphism influenced rapid response to antidepressant therapy . Compared with homozygous carriers of the 10-repeat allele , carriers of the 9/10 genotype had an odds ratio ( OR ) calculated by logistic regression analysis of 1.6 ( 95 % CI 0.8–3.2 ) and carriers of the 9/9 genotype had an OR of 6.0 ( 1.5–24.4 ) for no or poor response . Further studies are required to confirm this clinical association and to eluci date the underlying mechanisms Background In this study the predictive value of the combined dexamethasone/CRH test ( DEX/CRH test ) for acute antidepressant response was investigated . Methodology /Principal Findings In 114 depressed in patients suffering from unipolar or bipolar depression ( sample 1 ) the DEX/CRH test was performed at admission and shortly before discharge . During their stay in the hospital patients received different antidepressant treatment regimens . At admission , the rate of nonsuppression ( basal cortisol levels > 75.3 nmol/l ) was 24.6 % and was not related to the later therapeutic response . Moreover , 45 out of 114 ( 39.5 % ) patients showed an enhancement of HPA axis function at discharge in spite of clinical improvement . In a second sample , 40 depressed patients were treated either with reboxetine or mirtazapine for 5 weeks . The DEX/CRH test was performed before , after 1 week , and after 5 weeks of pharmacotherapy . Attenuation of HPA axis activity after 1 week was associated with a more pronounced alleviation of depressive symptoms after 5-week mirtazapine treatment , whereas downregulation of HPA system activity after 5 weeks was related to clinical response to reboxetine . However , early improvement of HPA axis dysregulation was not necessarily followed by a beneficial treatment outcome . Conclusions / Significance Taken together , performance of a single DEX/CRH test does not predict the therapeutic response . The best predictor for response seems to be an early attenuation of HPA axis activity within 1 or 2 weeks . However , early improvement of HPA system dysfunction is not a sufficient condition for a favourable response . Since a substantial part of depressive patients display a persistence of HPA axis hyperactivity at discharge , downregulation of HPA system function is not a necessary condition for acute clinical improvement either . Our data underline the importance of HPA axis dysregulation for treatment outcome in major depression , although restoration of HPA system dysfunction seems to be neither a necessary nor a sufficient determinant for acute treatment response BACKGROUND Treatment studies of depression in residential care are limited . Reports of predictors of response are rare . In the largest nursing home prospect i ve antidepressant trial reported , we examined predictors of response . METHODS This was a 12-week open-label study of mirtazapine orally disintegrating tablets performed in 30 US nursing homes . Subjects were men and women aged > or=70 , with a Mini Mental State Exam ( MMSE ) score > or=10 , who had a depressive disorder that required antidepressant treatment .  Mirtazapine was started at 15 mg at bedtime , and adjusted to 15 - 45 mg/day . A 16-item Hamilton Depression Rating Scale was used to assess depression at baseline , weeks 2 , 4 , 8 , and 12 or early termination . RESULTS One hundred and twenty-four patients received at least one dose of study drug and of these , 119 had at least one post-drug assessment . Mean age was 82.9 years and 72 % were female .  Response rates at 12 weeks were 47 % on the HAMD and 54 % on the CGI . Age , sex , MMSE score , medical burden , history of prior depression , and baseline HAMD severity were not significantly associated with HAMD response ( > or=50 % improvement ) and in most cases correlations were trivial , < 0.1 . Advanced age , medical burden , and cognitive impairment did not predict adverse events . CONCLUSIONS In this sample of depressed nursing home residents treated with mirtazapine orally disintegrating tablets , advanced age , medical illness , and cognitive impairment did not predict response . The findings suggest that these variables need not be viewed as obstacles to treatment The aim of this multicenter , r and omized , double-blind , 8-week study was to compare the antidepressant efficacy and tolerability of mirtazapine and venlafaxine in the treatment of hospitalized patients with DSM-IV diagnosis of severe depressive episode with melancholic features . Patients with a baseline score of ≥ 25 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) were r and omly assigned to receive treatment with either mirtazapine ( N = 78 , 15–60 mg/day ) or venlafaxine ( N = 79 , 75–375 mg/day , twice a day ) in a rapid up-titration schedule . Efficacy was assessed with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , HAM-D-17 , and Clinical Global Impression scale , and quality of life was assessed with the Quality of Life , Enjoyment , and Satisfaction Question naire and Quality of Life in Depression Scale . Tolerability was assessed with the Utvalg for Kliniske Undersogelser ( UKU ) side effect scale and by reporting adverse events . Both drugs were effective in reducing overall symptoms of depression , showing substantial reductions in group mean MADRS scores ( −20.1 for mirtazapine and −17.5 for venlafaxine ) and HAM-D-17 scores ( −17.1 for mirtazapine and −14.6 for venlafaxine ) at the end of the treatment . Although not statistically significant , at all assessment times higher percentages of patients treated with mirtazapine were classified as responders ( ≥50 % reduction ) on the HAM-D ( at endpoint , 62 % vs. 52 % ) and MADRS ( at endpoint : 64 % vs. 58 % ) . Likewise were the percentages of remitters ( HAM-D score ≤7 ; MADRS score ≤12 ) also higher in the mirtazapine group . A statistically significant difference favoring mirtazapine was found on the HAM-D Sleep Disturbance factor at all assessment points ( p ≤ 0.03 ) . Both treatments were well tolerated . Although slightly more subjects treated with mirtazapine reported at least one adverse event , a statistically significantly higher percentage of patients treated with venlafaxine ( 15.3 % ) than mirtazapine ( 5.1 % ) dropped out because of adverse events ( p = 0.037 ) . Quality of life improved in both treatment groups . In this study , treatment with mirtazapine result ed in a trend toward more responders and remitters than treatment with venlafaxine and in significantly fewer dropouts as a result of adverse events BACKGROUND Approximately 45 % of patients with major depressive disorder ( MDD ) do not remit when treated with biogenic amine antidepressants . Consequently , there is a significant need for antidepressant agents with different mechanisms of action . Early proof of concept ( POC ) studies with such novel agents play a significant role in helping drug developers identify agents and mechanisms of action that merit more intensive research . Studies have demonstrated that high affinity N-methyl-Daspartate ( NMDA ) receptor blockers ( eg , ketamine ) can produce rapid antidepressant effects in patients who have not responded to currently available agents , but treatment with these agents is accompanied by psychotomimetic effects that make their use problematic . This column describes a POC study involving GLYX-13 , an N-methyl-D-aspartate receptor glycine site functional partial agonist . METHOD In this double-blind , r and omized , placebo-controlled study , a single intravenous ( IV ) dose of GLYX-13 ( 1 , 5 , 10 , or 30 mg/kg ) or placebo was administered to 116 subjects with MDD who had not benefitted from a trial of at least one biogenic amine antidepressant during the current episode . The primary outcome measure was score on the Hamilton Depression Rating Scale-17 ( Ham-D17 ) , which was used to rate overall depressive symptoms at baseline and at 24 hours and days 3 , 7 , 14 , and , in some arms , days 21 and 28 after administration . RESULTS GLYX-13 , 5 or 10 mg/kg IV , reduced depressive symptoms as assessed by the Ham-D17 at days 1 through 7 . Onset of action as assessed using the Bech-6 occurred within 2 hours . GLYX-13 did not elicit psychotomimetic or other significant side effects . CONCLUSION In this early POC study , GLYX-13 reduced depressive symptoms within 2 hours and this effect was maintained for 7 days on average in subjects with MDD who had not responded to another antidepressant agent during the current depressive episode . The findings of this study support the hypothesis that modulation of the NMDA receptor is a valid target for the development of antidepressant drugs and the need for additional studies to further evaluate the effects of GLYX-13 . POC studies such as the one described here play a pivotal role in allowing drug research ers to decide whether to move forward with larger and more expensive studies , and they enable them to focus available re sources on those molecules that appear to have the most therapeutic promise . Based on the POC study described here , a multiple dose study has been completed which showed sustained therapeutic benefit with repeated dosing of GLYX-13 for more than 6 weeks . Phase 3 studies are now being planned INTRODUCTION Bipolar patients with breakthrough major depressive episodes despite ongoing adequately-dosed mood stabilizer medication were r and omized in a double-blind manner to one of three antidepressants with different mechanisms of action : bupropion , sertraline , or venlafaxine . Preliminary data are presented on the switch rates into hypomania or mania for the antidepressants as a group prior to unblinding the specific individual drug efficacy and tolerability data in this ongoing clinical trial . METHODS Subjects included 64 bipolar patients who participated at five sites in a 10-week double-blind trial for depression and a 1-year blinded continuation maintenance phase for responders . Nonresponders were re-r and omized such that there were 95 acute treatment phases . In the acute phase , doses were titrated to clinical response , side effects , or maximum dose of bupropion ( 450 mg/day ) , sertraline ( 200 mg/day ) , or venlafaxine ( 375 mg/day ) . Daily ratings on the National Institute of Mental Health-Life Chart Methodology ( NIMH-LCM ) were inspected for the degree of improvement on the Clinical Global Impressions scale as revised for bipolar illness ( CGI-BP ) and the occurrence of hypomania or mania . RESULTS Thirty-five ( 37 % ) of the 95 acute treatment phases were associated with a much or very much improved rating in depression on the CGI-BP . Thirteen ( 14 % ) of these 95 acute trials of antidepressants as adjuncts to mood stabilizers were associated with switches , seven into hypomania and six into mania . Forty-two patients elected to go into the continuation phase in 48 instances . Sixteen ( 33 % ) of the continuation phase trials were associated with mood switches , 10 into hypomania and six into mania . CONCLUSIONS In this r and omized double-blind prospect i ve study of three second-generation antidepressants ( bupropion , sertraline , and venlafaxine ) in bipolar patients whose depression broke through ongoing treatment with mood stabilizers , switches into hypomania or mania occurred in 14 % of the acute phases and 33 % of the continuation phases . Individual data on each drug will be assessed in the next phase of the study after more subjects are recruited and the blind is broken Aim Brain-derived neurotrophic factor ( BDNF ) is associated with antidepressant response on the cellular level , in animal models , and in clinical studies . A common variant in the BDNF gene results in a substitution of a methionine ( Met ) for a valine at the amino acid position 66 . Previous studies reported that the Met variant results in enhanced response to antidepressant medications . These findings may be at odds with studies indicating that on a cellular level the Met variant impairs the secretion of BDNF . Material s and methods We examined the effects of BDNF single nucleotide polymorphisms ( SNPs ) in response to the antidepressants paroxetine and mirtazapine in a sample of 246 geriatric patients with major depression , treated in a double-blind , r and omized , 8-week clinical trial . We also examined the effects of genetic variation at the BDNF-related loci neurotrophic tyrosine kinase receptor 2 , cyclic AMP responsive element binding protein 1 ( CREB1 ) , and CREB binding protein . A total of 53 SNPs were genotyped . Results BDNF genetic variation had a significant effect on the efficacy of paroxetine , with patients carrying the Met allele showing impaired response . SNPs at the CREB1 locus , which encodes a transcription factor important in BDNF signaling , also predicted response to paroxetine . Furthermore , we found a significant gene – gene interaction between BDNF and CREB1 that affected response to paroxetine . Because BDNF has been associated with cognitive function , we tested the effects of BDNF SNPs on change in a wide variety of cognitive tests over the 8-week trial , but there were no significant effects of genotype on cognition . Conclusion These results provide new evidence for the importance of the BDNF pathway in antidepressant response in geriatric patients . The negative effect of the Met66 allele on antidepressant outcomes is consistent with basic science findings indicating a negative effect of this variant on BDNF activity in the brain . Further , the effect of BDNF genetic variation on antidepressant treatment is modified by variation in the gene encoding the downstream effector CREB1 We performed an open-label single-institution phase II trial of mirtazapine ( 15 - 30 mg by mouth [ po ] every day [ qd ] ) , a tetracyclic antidepressant that may lead to weight gain , for 8 weeks in nondepressed patients with cancer-related cachexia/anorexia ( CRCA ) . The primary end point was the proportion of patients who gained ≥1 kg at week 4 . Secondary end points were quality of life and appetite . From June 2006 to July 2007 , 17 of 58 eligible patients were enrolled . On intention-to-treat analysis at week 4 , 4 of 17 patients ( 24 % ) gained 1 kg or more , 1 patient maintained weight ( gain of 400 g ) and 2 patients lost weight ( 800 g and 1.2 kg ) ; 24 % and 6 % improved appetite and health-related quality of life ( HQOL ) , respectively . Mirtazapine is a promising agent for the treatment of CRCA BACKGROUND Mirtazapine , an antidepressant with a broad spectrum of receptor affinity may , if combined with first generation antipsyhotics ( FGAs ) , improve clinical profile of the FGAs . However , potentiation of the antipsychotic effect by mirtazapine has not been reported thus far . We explored the efficacy of adjunctive mirtazapine on symptoms of schizophrenia in patients having an insufficient response to different FGAs . METHODS Schizophrenia-diagnosed patients with a prolonged disease and a history of a poor response to numerous antipsychotics , who were at least moderately ill despite their FGAs treatment , received add-on mirtazapine ( n=20 ) or placebo  ( n=19 ) in a 6-week double-blind r and omized controlled trial ( RCT ) . The analysis was made on a Modified Intent-to-Treat ( MITT ) basis with Last Observations Carried Forward ( LOCF ) . RESULTS Mirtazapine outranged placebo on almost all measures . The clear-cut clinical relevance of this finding was demonstrated by a large effect size of 1.00 ( 95 % CI 0.23 - 1.67 , p=0.003 ) on the total Positive and Negative Syndrome Scale ( PANSS ) scores ( the primary outcome ) . The PANSS positive subscale scores decreased by 17.2 % with mirtazapine vs. 1.6 % with placebo ( p<0.001 ) , and the PANSS negative subscale scores by 12 % and 3 % ( p<0.001 ) , correspondingly . CONCLUSIONS This is the first RCT reporting a robust additive antipsychotic effect of an adjunctive antidepressant . Mirtazapine-FGAs combination appears to be a safe , well-tolerated and efficacious treatment option in this challenging population . These findings are important due to the current re-emerging attention to FGAs . The focus of further studies should be exp and ed to include combinations with or switching to novel antipsychotics , different sub population s of patients with schizophrenia , finding of optimal doses , and comparison with clozapine OBJECTIVE The aim of the present study was to examine the influence of reboxetine and mirtazapine on psychomotor functions related to driving skills and on driving simulator performance in depressed in patients . METHOD Forty depressed in patients diagnosed according to DSM-IV-TR criteria were r and omly assigned to treatment with either reboxetine ( N = 20 ) or mirtazapine ( N = 20 ) . To control for retest effects in psychomotor measures , a group of 10 healthy controls was examined on the same time schedule . Participants were tested once before pharmacologic treatment and twice after initiation of treatment ( days 7 and 14 ) with computerized tests related to car-driving skills .  Data were collected with the Act and React Testsystem ART-90 and the Wiener Testsystem , measuring visual perception , reactivity , stress tolerance , concentration , and vigilance . In addition , patients went through various risk simulations on a static driving simulator . Data were analyzed with nonparametric statistics and repeated- measures analysis of variance . The study was conducted from June 2004 through June 2006 . RESULTS Before onset of treatment with antidepressants , about 65 % of patients did not reach the threshold criterion according to the German guidelines for road and traffic safety . After 14 days of treatment with reboxetine or mirtazapine , patients improved in driving ability skills . Controlling for retest effects in psychomotor measures , data indicate that both patient groups significantly improved in tests measuring selective attention and reactivity ( all p < .01 ) . Furthermore , the frequency of accidents in the risk simulations markedly decreased in patients receiving mirtazapine and reboxetine ( all p < .05 ) . Statistically significant differences between treatment groups could not be shown . CONCLUSION Our results indicate that partially remitted depressed in patients treated with reboxetine or mirtazapine show a better performance on tasks related to driving skills than do untreated depressives The development of therapeutic strategies to effectively treat negative symptoms remains one of the primary goals in the treatment of schizophrenia .  Mirtazapine is the first of a new class of dual action compounds , the noradrenergic and specific serotonergic antidepressants ( NaSSa ) , whose activity is related to the enhancement of noradrenergic and serotonergic transmission by a presynaptic & agr;2 antagonism and postsynaptic 5-HT2 and 5-HT3 antagonism , respectively . This study was a 8-week double-blind , r and omized , placebo-controlled trial of 30 mg adjunctive mirtazapine to clozapine therapy in 24 patients with DSM-IV schizophrenia . The main finding at the end of the trial was a significant reduction on the Scale for the Assessment of Negative Symptoms ( SANS ) total scores in the mirtazapine group compared to placebo ( P<0.01 ) with a significant improvement on the SANS subscales avolition/apathy and anhedonia/asociality . The Brief Psychiatric Rating Scale total score at week 8 showed superiority of mirtazapine over placebo . These findings suggest a potential role for mirtazapine as an augmentation strategy in the treatment of negative symptoms of schizophrenia Lowering the concentrations of free cortisol in depressed patients may be an important prerequisite to prevent glucocorticoid-related sequelae of depression . We tested the hypothesis that the hypothalamus-pituitary-adrenal ( HPA ) system-dampening effects of venlafaxine and mirtazapine differ . We compared the course of morning ( 08.00h ) and afternoon saliva cortisol ( 16.00h ) in 42 mirtazapine- and 45 venlafaxine-treated depressed patients during a 1-week wash-out and a 4-week treatment period in a r and omised open trial . Mirtazapine lowered afternoon cortisol from week 1 to 4 . In contrast , during the course of the entire treatment period , venlafaxine did not attenuate saliva cortisol concentrations . Treatment effects of mirtazapine on cortisol concentrations did not differ in remitters and non-remitters to treatment . High baseline cortisol concentrations , on the other h and , were related to an unfavourable course during venlafaxine treatment and patients remitting during venlafaxine treatment had significantly lower afternoon cortisol concentrations in saliva , when compared to non-remitting patients . Thus , mirtazapine and venlafaxine show different effects on HPA system activity as measured by saliva cortisol . This may be of relevance with regard to physical sequelae of depression BACKGROUND Depression is a common and costly comorbidity in dementia . There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes . AIMS To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia . METHOD A pragmatic , multicentre , r and omised placebo-controlled trial with a parallel cost-effectiveness analysis ( trial registration : IS RCT N88882979 and EudraCT 2006 - 000105 - 38 ) . The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline , mirtazapine or placebo  with differences in effectiveness measured by the primary outcome , total Cornell Scale for Depression in Dementia ( CSDD ) score , over two time periods : 0 - 13 weeks and 0 - 39 weeks . The secondary evaluation was a cost-utility analysis using quality -adjusted life years ( QALYs ) computed from the Euro-Qual ( EQ-5D ) and societal weights over those same periods . RESULTS There were 339 participants r and omised and 326 with costs data ( 111 placebo , 107 sertraline , 108 mirtazapine ) . For the primary outcome , decrease in depression , mirtazapine and sertraline were not cost-effective compared with placebo . However , examining secondary outcomes , the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo ( 6.74 v. 12.27 hours per week ) or sertraline ( 6.74 v. 12.32 hours per week ) . Informal care costs over 39 weeks were £ 1510 and £ 1522 less for the mirtazapine group compared with placebo and sertraline respectively . CONCLUSIONS In terms of reducing  depression  , mirtazapine and sertraline were not cost-effective for treating depression in dementia . However , mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome . Unpaid ( family ) carer costs were lower with mirtazapine than sertraline or placebo . This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety . Given the priority and the potential value of supporting family carers of people with dementia , further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers PURPOSE We studied the effect of 3 antidepressant treatments on outcomes ( depressive severity , medication tolerability , and psychosocial functioning ) in depressed patients having comorbid general medical conditions in the Combining Medications to Enhance Depression Outcomes ( CO-MED ) trial . METHODS Adult out patients who had chronic and /or recurrent major depressive disorder ( MDD ) with and without general medical conditions were r and omly assigned in 1:1:1 ratio to 28 weeks of single-blind , placebo-controlled antidepressant treatment with ( 1 ) escitalopram plus placebo , ( 2 ) bupropion-SR plus escitalopram , or ( 3 ) venlafaxine-XR plus mirtazapine . At weeks 12 and 28 , we compared response and tolerability between participants with 0 , 1 , 2 , and 3 or more general medical conditions . RESULTS Of the 665 evaluable patients , 49.5 % reported having no treated general medical conditions , 23.8 % reported having 1 , 14.8 % reported having 2 , and 11.9 % reported having at least 3 . We found only minimal differences in antidepressant treatment response between these groups having different numbers of conditions ; patients with 3 or more conditions reported higher rates of impairment in social and occupational functioning at week 12 but not at week 28 . Additionally , we found no significant differences between the 3 antidepressant treatments across these groups . CONCLUSIONS Patients with general medical conditions can be safely and effectively treated for MDD with antidepressants with no additional adverse effect or tolerability burden relative to their counterparts without such conditions . Combination therapy is not associated with an increased treatment response beyond that found with traditional monotherapy in patients with MDD , regardless of the presence and number of general medical conditions INTRODUCTION Sexual dysfunction is common with serotonergic antidepressants , including selective serotonin reuptake inhibitors ( SSRIs ) and serotonin-norepinephrine reuptake inhibitors ( SNRIs ) , and does not resolve in most patients . Vortioxetine , an antidepressant with a multimodal mechanism of action , has shown low rates of sexual dysfunction in previous major depressive disorder ( MDD ) trials . AIM This study compared the effects of vortioxetine and escitalopram on sexual functioning in adults with well-treated MDD experiencing treatment-emergent sexual dysfunction ( TESD ) . METHODS Participants treated with , and responding to , citalopram , paroxetine , or sertraline were r and omized to switch to either vortioxetine ( 10/20 mg ; n = 225 ) or escitalopram ( 10/20 mg ; n = 222 ) for 8 weeks . Sexual function was assessed using the Changes in Sexual Functioning Question naire Short Form ( CSFQ-14 ) , and antidepressant efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , Clinical Global Impressions ( CGI ) scale , and Profile of Mood States brief form ( POMS-brief ) . Safety and tolerability were also assessed . MAIN OUTCOME MEASURES The primary endpoint was change from baseline in the CSFQ-14 total score after 8 weeks of treatment . The MADRS , CGI , and POMS-brief were used to assess antidepressant efficacy . Safety was assessed via adverse events , vital signs , electrocardiograms , laboratory values , weight , and physical examination findings . RESULTS Vortioxetine showed significantly greater improvements in CSFQ-14 total score ( 8.8 ± 0.64 , mean ± st and ard error ) vs. escitalopram ( 6.6 ± 0.64 ; P = 0.013 ) . Benefits vs. escitalopram were significant on four of five dimensions and all three phases of sexual functioning assessed by the CSFQ-14 ( P < 0.05 ) . Antidepressant efficacy continued in both groups , with similar , but slight , improvements in MADRS and CGI scores . Vortioxetine and escitalopram had similar clinical efficacy profiles in this study , with safety profiles similar to previous trials . Nausea ( n = 9 , 4.0 % ) was the most common treatment-emergent adverse event leading to discontinuation of vortioxetine . CONCLUSION Switching antidepressant therapy to vortioxetine may be beneficial for patients experiencing sexual dysfunction during antidepressant therapy with SSRIs Introduction Erythropoietin ( Epo ) has neurotrophic effects and may be a novel therapeutic agent in the treatment of depression . We have found antidepressant-like effects of Epo on emotional processing and mood in healthy volunteers . Objective The current study aim ed to explore the effects of Epo on the neural processing of emotional information in depressed patients . Material s and methods Seventeen patients with acute major depressive disorder were r and omised to receive Epo ( 40,000 IU ) or saline iv in a double-blind , parallel-group design . On day 3 , we assessed neural responses to positive , negative and neutral pictures during fMRI followed by picture recall after the scan . Mood and blood parameters were assessed at baseline and on day 3 . Results Epo reduced neural response to negative vs. positive pictures 3 days post-administration in a network of areas including the hippocampus , ventromedial prefrontal and parietal cortex . After the scan , Epo-treated patients showed improved memory compared with those that were given placebo . The effects occurred in the absence of changes in mood or haematological parameters , suggesting that they originated from direct neurobiological actions of Epo . Conclusions These findings are similar to the effects of conventional antidepressants and opposite to the negative biases in depression . The central effects of Epo therefore deserve further investigation as a potential antidepressant mechanism Spectral analysis of fluctuations in heart rate ( HR ) and blood pressure ( BP ) was applied to assess sympathetic and parasympathetic cardiovascular control mechanisms in patients with unipolar affective disorder before and after treatment with imipramine ( IMI ) or mirtazapine ( MIR ) .  In a double-blind r and omized study , 10 patients received treatment with IMI and 10 patients received treatment with MIR .  Cardiovascular parameters were studied before and after 4 weeks of treatment :  HR and BP ( Finapres ) were recorded continuously during supine rest ( SR ) and orthostatic challenge ( OC ; 60-degrees head-up tilting ) . During SR and OC , power spectra were calculated for HR and systolic BP . Spectral density was assessed for three frequency b and s : low ( 0.02 - 0.06 Hz ) , mid ( 0.07 - 0.14 Hz ) , and high ( 0.15 - 0.50 Hz ) . Before treatment , the depressed patients ( N = 20 ) differed from age-matched controls ( N = 20 ) only in their response to OC : the depressed patients showed more suppression of HR variability ( both mid- and high-frequency b and fluctuations ) , indicating stronger vagal inhibition , and a reduced increase of BP variability ( mid-frequency b and fluctuations ) , indicating reduced sympathetic activation . After 4 weeks of treatment , patients treated with either antidepressant drug showed significant changes of HR ( increase ) and HR variability ( decrease ) during SR and OC ; the suppression of mid- and high-frequency fluctuations of HR was larger for IMI than for MIR . The increase in HR and decrease in HR variability may be attributed to the anticholinergic properties of IMI ( strong ) and MIR ( weak ) , result ing in cardiac vagal inhibition . Whereas MIR had no effect on BP or BP variability , IMI specifically reduced mid-frequency b and fluctuations of BP as the result of a suppression of central sympathetic activity . Our data confirm and extend previous observations on the presence of autonomic dysfunctions in unmedicated depressed patients : spectral analysis of HR and BP fluctuations suggested that both parasympathetic and sympathetic mechanisms are involved , specifically during OC . The preexisting autonomic cardiovascular dysfunctions were not normalized by antidepressant drugs . In fact , some of the components of the cardiovascular autonomic dysfunction were further aggravated , depending on the pharmacologic profile of the drug under investigation OBJECTIVE Several evidence -based treatment guidelines for major depressive disorder ( MDD ) have been published . However , little is known about how recommendations for treatment are adhered to by patients in current usual psychiatric practice . METHOD The Vantaa Depression Study is a prospect i ve , naturalistic cohort study of 269 psychiatric patients with a new episode of DSM-IV MDD who were interviewed with the Schedules for Clinical Assessment in Neuropsychiatry and Structured Clinical Interview for DSM-III-R Personality Disorders between February 1 , 1997 , and May 31 , 1998 , and again at 6 and 18 months . Treatments provided , as well as adherence to and attitudes toward both antidepressants and psychotherapeutic support/psychotherapy , were investigated among the 198 unipolar patients followed for 18 months . RESULTS Most depression patients ( 88 % ) received antidepressants in the early acute phase , but about half ( 49 % ) terminated treatment prematurely . This premature termination was associated with worse outcome of major depressive episodes , and with negative attitudes , mainly explained by fear of dependence on or side effects of antidepressants . Nearly all patients ( 98 % ) received some  psychosocial treatment  in the acute phase ; about one fifth ( 16 % ) had weekly psychotherapy  during the follow-up . About a quarter of patients admitted nonadherence to ongoing treatments . CONCLUSION Problems of psychiatric care seem most related to continuity of treatment . While adequate treatments are provided in the early acute phase , antidepressants are terminated too soon in about half of patients , often following their autonomous decisions . From a secondary and tertiary preventive point of view , improving continuity of treatment would appear a crucial task for improving the outcome of psychiatric patients with MDD Depression is an independent risk factor for post myocardial infa rct ion ( MI ) mortality . Abnormalities in platelet function have been proposed as one of the mechanisms involved in increased cardiovascular risk among patients with depression post-MI . Depression in somatically healthy patients has been associated with increased platelet activation . Some but not all studies showed changes in blood serotonin level . Increased platelet activation and blood serotonin level have been associated with increased risk of cardiac events in patients with MI . The goal of this study was to investigate whether 1 ) depressed post-MI patients have higher markers of platelet activation as measured by plasma levels of beta-thromboglobulin ( betaTG ) , platelet factor 4 ( PF4 ) and soluble CD40 lig and ( sCD40L ) and higher serotonin ( 5-HT ) levels than non-depressed post-MI patients and 2 ) treatment with the antidepressant mirtazapine decreases platelet activation . In this study , 25 depressed post-MI patients were asked for blood collection before start as well as after 8 weeks treatment with mirtazapine or placebo . The control group ( n=22 ) consisted of non-depressed post-MI patients , matched for age , gender and time elapsed since MI . Plasma levels of betaTG , PF4 and sCD40L were not statistically different between the groups , but 5-HT levels were significantly higher in depressed patients . Treatment with mirtazapine result ed in a non-significant decrease in betaTG and PF4 and platelet 5-HT levels . Platelet and whole blood 5-HT , but not platelet activation was significantly increased in depressed post-MI patients . Treatment with mirtazapine showed a non-significant decrease in platelet activation and platelet 5-HT Serotonin-norepinephrine reuptake inhibitors ( SNRIs ) may be used as an alternative treatment for depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant . This r and omized , open-label , multicenter study compared the effectiveness of the SNRI venlafaxine extended release ( VXR ) with that of conventional antidepressants ( CA ) in patients who were referred to an outpatient psychiatric specialty care setting for treatment after failure to tolerate or respond to at least 4 weeks of treatment with a CA in a primary care setting . Patients with a Hamilton Depression Rating Scale ( HAM-D17 ) score > or = 17 were r and omly assigned to treatment with an alternative CA or VXR .  Remission was defined as a score < or = 7 on the HAM-D17 . Efficacy analyses were carried out on 3,097 patients from the intent-to-treat ( ITT ) population ( 1,632 VXR ; 1,465 CA ) . The antidepressants prescribed most frequently in the CA group were paroxetine ( 21.3 % ) , citalopram ( 20.1 % ) , sertraline ( 19.1 % ) , fluoxetine ( 17.0 % ) , and mirtazapine ( 7.9 % ) . After 24 weeks of treatment , the VXR group demonstrated a significantly higher remission rate than did the CA group ( 59.3 % VXR ; 51.5 % CA ; P<.0001 ; odds ratio : 1.37 ; 95 % CI : 1.19 - 1.58 ; P<.01 ) . Despite the limitations of the open design , the results of this study suggest that venlafaxine extended release may be more effective than the conventional antidepressants used in this study when treating depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant OBJECTIVE Depression following myocardial infa rct ion is associated with an increased risk of cardiac events , but attempts to alter cardiovascular prognosis by providing antidepressive treatment have not been successful . This may be because of the limited effects of antidepressive treatment on depression itself . The authors assessed whether nonresponse to treatment of post-myocardial infa rct ion depression is associated with new cardiac events . METHOD The authors made a subgroup analysis of a multicenter r and omized , clinical trial on the effects of antidepressant treatment for post-myocardial infa rct ion depression . Patients were enrolled in double-blind , placebo-controlled treatment with mirtazapine ( 30 mg/day ) and , in the case of insufficient treatment response after 8 weeks , open treatment with citalopram . Patients were classified as responders to antidepressants ( at least 50 % reduction in Hamilton Depression Rating scale [ HAM-D ] score or HAM-D score < 9 at 24 weeks ) ( N=43 ) or as nonresponders ( N=27 ) and compared to untreated control subjects ( N=98 ) on cardiac events ( cardiac mortality or cardiac-related hospital admission ) after 24 weeks post-r and om assignment and within 18 months after index infa rct ion . RESULTS The event rate was 25.6 % among nonresponders , 11.2 % among untreated control subjects , and 7.4 % among responders . In relation to untreated comparison subjects , nonresponders had a hazard ratio of 2.66 for new cardiovascular events , which remained after the authors controlled for potential confounders ( hazard ratio=2.92 ) . CONCLUSIONS This study provides further preliminary evidence that nonresponse to treatment of post-myocardial infa rct ion depression may be associated with cardiac events . Efforts should be dedicated to developing more effective treatments for depressed patients with myocardial infa rct ion Depressive disorders are a major health care issue and one of the foremost causes of disability in adults around the world , result ing in significant costs to society and health care systems ( 1 ) . The estimated economic burden associated with depression was $ 83.1 billion in 2000 and is probably higher today ( 2 ) . Depressive disorders include major depressive disorder ( MDD ) ; dysthymia ; and subsyndromal depression , including minor depression . Major depressive disorder is the most prevalent depressive disorder , with an estimated lifetime prevalence of 16 % in the United States ( 3 ) . An average of 8 million ambulatory care visits per year result in a primary diagnosis of MDD ( 4 ) . The American Psychiatric Association ( 5 ) defines MDD as depressed mood or loss of pleasure or interest along with other symptoms , including significant change in weight or appetite , insomnia or hypersomnia , psychomotor agitation or retardation nearly every day , fatigue or loss of energy , feelings of worthlessness or excessive or inappropriate guilt , indecisiveness or decreased ability to concentrate , and recurrent thoughts of death or suicide , that last for at least 2 weeks and affect normal functioning . Dysthymia is less severe , but symptoms last for 2 or more years . In contrast , subsyndromal depression is associated with less severe symptoms of depression that do not qualify for MDD or dysthymia diagnoses . The treatment of depression can be characterized by 3 phases ( Figure 1 ) : acute ( 6 to 12 weeks ) , continuation ( 4 to 9 months ) , and maintenance ( 1 year ) ( 7 ) . Relapse is defined as the return of depressive symptoms during the acute or continuation phases and is therefore considered part of the same depressive episode , whereas recurrence is defined as the return of depressive symptoms during the maintenance phase and is considered a new , distinct episode . Response to treatment ( typically defined as 50 % reduction in measured severity ) can be quantified using various tools , such as the Patient Health Question naire-9 ( PHQ-9 ) ( 7 ) or the Hamilton Depression Rating Scale ( HAM-D ) ( 8) . Figure 1 . Phases of treatment of major depression . Adapted from reference 6 . TX = treatment . Various treatment approaches can be used to manage MDD , such as psychotherapy , complementary and alternative medicine ( CAM ) , exercise , and pharmacotherapy . The psychological interventions used to treat depression include acceptance and commitment therapy , cognitive therapy , cognitive behavioral therapy ( CBT ) , interpersonal therapy , and psychodynamic therapies ( Table 1 ) . The CAM treatments include acupuncture , meditation , -3 fatty acids , S-adenosyl-l-methionine ( SAMe ) , St. John 's wort , and yoga . Exercise includes a broad range of activities that can be done for varying duration s , in classes , individually , or in informal groups . For pharmacologic therapy , the scope of this guideline is limited to second-generation antidepressants ( SGAs ) ( selective serotonin reuptake inhibitors , serotonin norepinephrine reuptake inhibitors , and selective serotonin norepinephrine reuptake inhibitors ) . First-generation antidepressants ( tricyclic antidepressants and monoamine oxidase inhibitors ) are very rarely used because SGAs have lower toxicity in overdose than first-generation antidepressants and similar efficacy . Table 1 . Common Psychological Interventions to Treat Depression Guideline Focus and Target Population The purpose of this guideline from the American College of Physicians ( ACP ) is to summarize and grade the evidence on the comparative effectiveness and safety of nonpharmacologic treatments and SGAs ( including serotonin reuptake inhibitors , serotonin norepinephrine reuptake inhibitors , bupropion , mirtazapine , nefazodone , and trazodone ) , alone or in combination , for MDD . The target audience for this guideline includes all clinicians , and the target patient population includes all adults with MDD . These recommendations are based on a background evidence article ( 9 ) and a systematic evidence review sponsored by the Agency for Healthcare Research and Quality ( AHRQ ) ( 6 ) . Methods Systematic Review of the Evidence The systematic evidence review was conducted by the AHRQ 's RTI InternationalUniversity of North Carolina at Chapel Hill Evidence -based Practice Center ( 6 ) . Additional method ological details can be found in the Appendix ) , accompanying background evidence article ( 9 ) , and full report ( 6 ) . Review ers search ed several data bases for studies published in English , German , or Italian from 1 January 1990 through September 2015 . Studies on efficacy were limited to r and omized , controlled trials and systematic review s and meta-analyses , although evidence on harms included observational studies . Review ers combined data when possible using meta- analysis and assessed the risk of bias and quality of studies according to established methods . The study population included adult out patients ( aged 18 years ) with MDD during either an initial or a second treatment attempt who did not remit after an initial adequate trial with an SGA . The review evaluated the following classes of interventions : depression-focused psychotherapy , CAM , exercise , and SGAs . Outcomes assessed included benefits in response ( often defined as 50 % improvement in HAM-D scores ) , remission ( often defined as a HAM-D score 7 ) , speed of response , speed of remission , relapse , quality of life , functional capacity ( as assessed by various scales ) , reduction of suicidality , or reduction of hospitalization . Harms assessed included overall adverse events , withdrawals because of adverse events , serious adverse events , and specific adverse events . Quality of life , functional status , suicidality , and hospitalizations were rarely reported . Grading the Evidence and Developing Recommendations This guideline was developed by the ACP Clinical Guidelines Committee according to the ACP guideline development process , which has been described ( 10 ) . The Clinical Guidelines Committee used the evidence tables in the accompanying systematic review and full report ( 9 ) when reporting the evidence and grade d the recommendations using ACP 's guideline grading system ( Table 2 ) . Table 2 . The American College of Physicians ' Guideline Grading System * Peer Review The AHRQ evidence review was sent to invited peer review ers and posted on the AHRQ Web site for public comments . The guideline was peer- review ed through the journal and was posted online for comments from ACP Governors and Regents . Comparative Benefits of Pharmacologic Versus Nonpharmacologic Treatment Options for Initial Management Refer to Appendix Table 1 and the accompanying systematic review ( 9 ) for additional details of the evidence . Appendix Table 1 . First-Line Treatment for MDD : SGAs Versus Nonpharmacologic Therapies * SGA Versus Psychological Interventions SGA Versus CBT Monotherapy . Moderate- quality evidence from 5 trials ( 1115 ) showed no difference in response when comparing SGAs ( fluoxetine , fluvoxamine , paroxetine , or sertraline ) with CBT in patients with MDD after 8 to 52 weeks of treatment . Low- quality evidence from 3 trials ( 11 , 14 , 15 ) showed no difference between remission rates ( fluoxetine , fluvoxamine , and paroxetine ) and functional capacity ( 14 ) ( fluvoxamine and paroxetine ) for SGAs compared with CBT . Combination Therapy . Low- quality evidence from 2 trials ( 14 , 16 ) showed no difference in response or remission when comparing monotherapy using SGAs ( escitalopram , fluvoxamine , or paroxetine ) with combination therapy using SGAs plus CBT ( problem-solving therapy or telephone-based CBT ) in patients with MDD after 12 to 52 weeks of treatment . Low- quality evidence from 2 trials ( 14 , 16 ) assessed function , and 1 trial showed that patients who received the combination therapy reported more improvement on 3 of 5 work-functioning measures than those who received SGA monotherapy , although clinical ly important differences on these measures are uncertain . SGA Versus Interpersonal Therapy Monotherapy . Low- quality evidence showed no difference in response ( 1 trial ; escitalopram ) ( 17 ) or remission ( 2 trials ; citalopram , escitalopram , or sertraline ) ( 17 , 18 ) for SGAs compared with interpersonal therapy for patients with MDD after 12 weeks of treatment . Combination Therapy . Low- quality evidence from 1 trial ( 19 ) showed increased remission for SGA monotherapy compared with SGA combined with interpersonal therapy ( with nefazodone ) in patients with MDD after 12 weeks of treatment . SGA Versus Psychodynamic Therapies Monotherapy . Low- quality evidence from 1 trial ( 20 ) showed no difference in remission for fluoxetine compared with psychodynamic monotherapy in patients with MDD after 16 weeks of treatment . Low- quality evidence from 2 trials ( 20 , 21 ) showed few differences in functional capacity between the treatments . Combination Therapy . Low- quality evidence from 1 trial ( 21 ) showed no difference in functional capacity for SGA monotherapy compared with SGA plus psychodynamic combination therapy . SGA Versus CAM Interventions SGA Versus Acupuncture Monotherapy . Low- quality evidence from 2 trials ( 22 , 23 ) showed no difference in treatment response when comparing fluoxetine with acupuncture monotherapy for patients with MDD after 6 weeks of treatment . Combination Therapy . Low- quality evidence from 2 trials ( 24 , 25 ) showed that combination therapy of SGAs with acupuncture improved treatment response compared with monotherapy with SGAs ( fluoxetine or paroxetine ) in patients with MDD after 6 weeks of treatment . However , low- quality evidence from 1 trial ( 24 ) showed no difference in remission when comparing paroxetine monotherapy with paroxetine plus acupuncture combination therapy . SGA Versus -3 Fatty Acids Monotherapy . Low- quality evidence from network meta- analysis showed that SGAs ( fluoxetine ) were associated with a greater response than -3 fatty acids in patients with MDD .  SGA Versus SAMe Monotherapy . Low- quality evidence from network meta- analysis showed no difference in response between treatment with escitalopram Pre clinical investigations have shown that combined administration of the alpha 2-adrenergic receptor antagonist yohimbine hydrochloride and the tricyclic antidepressant desipramine hydrochloride produces a reduction in brain beta-adrenergic receptor function within four days . Since the ability of antidepressant treatments to reduce beta-adrenergic receptor function has been hypothesized to mediate antidepressant efficacy , it was predicted that combined desipramine-yohimbine treatment would be a more rapid-acting and potent antidepressant regimen than desipramine alone . In the present investigation , the effects of desipramine ( N = 11 ) and desipramine-yohimbine ( N = 10 ) treatment on depressive symptoms , norepinephrine turnover , and blood pressure were determined in patients with major depression who had a history of nonresponse to st and ard antidepressant treatments . Neither desipramine nor desipramine-yohimbine proved to be an effective treatment , although concomitant yohimbine administration did attenuate the ability of desipramine to decrease plasma free and 24-hour urinary 3-methoxy-4-hydroxyphenyl-ethyleneglycol levels and blood pressure . Fifteen of the 21 patients eventually had a good response to pharmacologic treatments , particularly a desipramine-lithium carbonate or lithium carbonate-tranylcypromine sulfate combination treatment ( 11 of 14 responded ) . This study provides evidence against the beta-adrenergic receptor hypothesis of antidepressant action Antidepressant medication is considered the current st and ard for severe depression , and cognitive therapy is the most widely investigated psychosocial treatment for depression . However , not all patients want to take medication , and cognitive therapy has not demonstrated consistent efficacy across trials . Moreover , dismantling design s have suggested that behavioral components may account for the efficacy of cognitive therapy . The present study tested the efficacy of behavioral activation by comparing it with cognitive therapy and antidepressant medication in a r and omized placebo-controlled design in adults with major depressive disorder ( N = 241 ) . In addition , it examined the importance of initial severity as a moderator of treatment outcome . Among more severely depressed patients , behavioral activation was comparable to antidepressant medication , and both significantly outperformed cognitive therapy . The implication s of these findings for the evaluation of current treatment guidelines and dissemination are discussed
Mirtazapine was significantly more effective than a serotonin-noradrenaline reuptake inhibitor ( venlafaxine only , two trials , n = 415 ) at two weeks ( OR 2.29 , 95 % CI 1.45 to 3.59 ) and at the end of acute-phase treatment ( OR 1.53 , 95 % CI 1.03 to 2.25).In terms of dropouts , there was no robust evidence to detect a difference between mirtazapine and other antidepressants .
Mirtazapine was more likely to cause weight gain or increased appetite and somnolence than SSRIs but less likely to cause nausea or vomiting and sexual dysfunction .
AUTHORS ' CONCLUSIONS Some statistically significant and possibly clinical ly meaningful differences between mirtazapine and other antidepressive agents were found for the acute-phase treatment of major depression .
Mirtazapine is likely to have a faster onset of action than SSRIs during the acute-phase treatment .
Dropouts occur similarly in participants treated with mirtazapine and those treated with other antidepressants , although the adverse event profile of mirtazapine is unique
BACKGROUND Mirtazapine has a unique mechanism of antidepressive action and is one of the commonly used antidepressants in clinical practice .
OBJECTIVES The aim of the present review was to assess the evidence on the efficacy and acceptability of mirtazapine compared with other antidepressive agents in the acute-phase treatment of major depression in adults .