Aripiprazole as augmentation treatment of refractory generalized anxiety disorder and panic disorder. Longitudinal outcome with pharmacotherapy in a naturalistic study of panic disorder. Poverty and response to treatment among panic disorder patients in primary care. Update on AUA guideline on the management of benign prostatic hyperplasia. An open-label trial of risperidone augmentation for refractory anxiety disorders. Next-step strategies for panic disorder refractory to initial pharmacotherapy: a 3-phase randomized clinical trial. One-year follow-up of pharmacotherapy-resistant patients with panic disorder treated with cognitive-behavior therapy: Outcome and predictors of remission. A randomized effectiveness trial of collaborative care for patients with panic disorder in primary care. Open‐Label Support for Duloxetine for the Treatment of Panic Disorder Strategy for treating selective serotonin reuptake inhibitor-resistant social anxiety disorder in the clinical setting: a randomised controlled trial protocol of cognitive behavioural therapy in combination with conventional treatment A randomized effectiveness trial of cognitive-behavioral therapy and medication for primary care panic disorder. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. II. Psychotherapy alone or in combination with antidepressant medication. Long-term outcome after acute treatment with alprazolam or clonazepam for panic disorder. Moclobemide is effective and well tolerated in the long-term pharmacotherapy of social anxiety disorder with or without comorbid anxiety disorder SECOND-STAGE TREATMENTS FOR RELATIVE NONRESPONDERS TO COGNITIVE BEHAVIORAL THERAPY (CBT) FOR PANIC DISORDER WITH OR WITHOUT AGORAPHOBIA-CONTINUED CBT VERSUS SSRI: A RANDOMIZED CONTROLLED TRIAL. Three year naturalistic outcome study of panic disorder patients treated with paroxetine Disorder-specific impact of coordinated anxiety learning and management treatment for anxiety disorders in primary care. Efficacy of D-Cycloserine for Enhancing Response to Cognitive-Behavior Therapy for Panic Disorder The expert consensus guideline series. Pharmacotherapy of depressive disorders in older patients. Medical illness and response to treatment in primary care panic disorder. Does physician education on depression management improve treatment in primary care? Refractory idiopathic urge urinary incontinence and botulinum A injection. Yoga on Our Minds: A Systematic Review of Yoga for Neuropsychiatric Disorders Does occasional cannabis use impact anxiety and depression treatment outcomes?: Results from a randomized effectiveness trial. Long-term opioid use in non-cancer pain. A change of paradigm in the treatment of low-severity alcohol-dependent patients. Does brief dynamic psychotherapy reduce the relapse rate of panic disorder? Incremental cost-effectiveness of a collaborative care intervention for panic disorder. Quetiapine augmentation of paroxetine CR for the treatment of refractory generalized anxiety disorder: preliminary findings PREFER study: a randomized clinical trial testing treatment preference and two dietary options in behavioral weight management--rationale, design and baseline characteristics. Treatment outcomes for primary care patients with major depression and lifetime anxiety disorders. Digital Education in Health Professions: The Need for Overarching Evidence Synthesis Anxiety diagnoses in smokers seeking cessation treatment: relations with tobacco dependence, withdrawal, outcome and response to treatment. Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. IV. Neurostimulation therapies. Effectiveness of mindfulness‐based cognitive therapy as an adjuvant to pharmacotherapy in patients with panic disorder or generalized anxiety disorder Suicide attempts in patients with bipolar I disorder during acute and maintenance phases of intensive treatment with pharmacotherapy and adjunctive psychotherapy. The effect of pharmacotherapist characteristics on treatment outcome in panic disorder. Maintenance treatment for old-age depression preserves health-related quality of life: a randomized, controlled trial of paroxetine and interpersonal psychotherapy. 2nd year maintenance and discontinuation of imipramine in panic disorder with agoraphobia. Treatment of borderline personality disorder in youth. Differential relapse following cognitive therapy and pharmacotherapy for depression. Does concurrent drug intake affect the long-term outcome of group cognitive behaviour therapy in panic disorder with or without agoraphobia? Antidepressant monotherapy vs sequential pharmacotherapy and mindfulness-based cognitive therapy, or placebo, for relapse prophylaxis in recurrent depression. Avoidance behaviour: A predictor of the efficacy of pharmacotherapy in panic disorder? Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians Panic and avoidance in agoraphobia. Application of path analysis to treatment studies. Predictors of response to pharmacotherapy with citalopram in obsessive-compulsive disorder European clinical guidelines for Tourette Syndrome and other tic disorders. Part III: behavioural and psychosocial interventions Design and Rationale for a Randomized Controlled Trial Testing the Efficacy of Aerobic Exercise for Patients with Obsessive-Compulsive Disorder. A comparative trial of psychotherapy and pharmacotherapy for "pure" dysthymic patients. Patients with panic disorder unaccompanied by depression improve with alprazolam and imipramine treatment. Treatment of pharmacotherapy-refractory posttraumatic stress disorder among Cambodian refugees: a pilot study of combination treatment with cognitive-behavior therapy vs sertraline alone. Two-year outcomes for interpersonal and social rhythm therapy in individuals with bipolar I disorder. British Dietetic Association evidence-based guidelines for the dietary management of irritable bowel syndrome in adults. The efficacy of reboxetine in the treatment-refractory patients with panic disorder: an open label study. Relapse and impairment in bipolar disorder. The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. Weight change in older depressed patients during acute pharmacotherapy with paroxetine and nortriptyline: a double-blind randomized trial. Group cognitive-behavioral treatment of panic disorder. A systematic review of anxiety interventions in stroke and acquired brain injury: Efficacy and trial design A randomized study of family-focused psychoeducation and pharmacotherapy in the outpatient management of bipolar disorder. Development of the Treatment Adherence Survey-patient version (TAS-P) for OCD. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the acute and continuation treatment of unipolar depressive disorders The efficacy of compliance therapy in pharmacotherapy for alcohol dependence: a randomized controlled trial. Cognitive-behavioral therapy helps prevent relapse and recurrence of panic disorder following alprazolam discontinuation: a long-term follow-up of the Peoria and Dartmouth studies.
INTRODUCTION Individuals with anxiety disorders often remain symptomatic despite treatment with a first-line pharmacologic agent . More research examining pharmacotherapy augmentation strategies to improve outcomes is needed . METHODS In an 8-week , open-label , prospect i ve augmentation study , we examined the efficacy and tolerability of the novel antipsychotic agent aripiprazole for adult out patients with generalized anxiety disorder ( n=13 ) or panic disorder ( n=10 ) who remained symptomatic despite treatment for at least 8 weeks with an adequate ( or maximally tolerated ) dose of typical pharmacotherapy . RESULTS Aripiprazole augmentation was associated with a significant reduction in Clinical Global Impressions-Severity scores ( paired t=4.41 , df=22 , P<.001 ) in the intent-to-treat sample of 23 individuals . Three subjects ( 13 % ) discontinued due to sedation , chest discomfort , and restlessness , respectively . CONCLUSION These data provide preliminary evidence that aripiprazole may be a useful augmentation strategy for individuals with generalized anxiety disorder or panic disorder who show a limited response to initial pharmacotherapy BACKGROUND Current recommendations suggest that pharmacotherapy for patients with panic disorder should be continued for at least 1 year [ Am . J. Psychiatry 155 ( 1998 ) 1 ] , despite a paucity of data systematic ally examining outcome for periods greater than 3 - 6 months . It is critically important to obtain more information on the effectiveness of medications over time for patients who initially responded to pharmacotherapy for panic disorder . METHODS Long-term outcome was examined for 78 patients who attained a 2-month period of sustained remission on medication and received maintenance pharmacotherapy for up to 24 months during the Massachusetts General Hospital Longitudinal Study of Panic Disorder , a prospect i ve , naturalistic study . Participants were categorized by their maintenance treatment condition at remission : benzodiazepine alone ( N = 45 , 58 % ) , antidepressant alone ( N = 12 , 16 % ) , and combined treatment with a benzodiazepine and an antidepressant ( N = 21 , 27 % ) . RESULTS Approximately half ( N = 36 , 46 % ) of the patients who had achieved remission relapsed at some time over the 2-year naturalistic study period , despite continued and adequate pharmacotherapy . There was no difference in timing or frequency of relapse by type of maintenance pharmacotherapy . LIMITATIONS Interpretation of the data is limited by the naturalistic nature of the study , and by the relatively low sample size . CONCLUSIONS This data suggests that patients with panic disorder have a high rate of relapse even after acute response to pharmacotherapy , despite continued treatment . In addition , the use of combined pharmacotherapy with antidepressants and benzodiazepines does not appear to provide greater protection from relapse than monotherapy OBJECTIVE Despite well-established links between poverty and poor mental illness outcome as well as recent reports exploring racial and ethnic health disparities , little is known about the outcomes of evidence -based psychiatric treatment for poor individuals . METHOD Primary care patients with panic disorder ( N=232 ) who were participating in a r and omized controlled trial comparing a cognitive behavior therapy ( CBT ) and pharmacotherapy intervention to usual care were divided into those patients above ( N=152 ) and below ( N=80 ) the poverty line .  Telephone assessment s  at 3 , 6 , 9 , and 12 months were used to compare the amount of evidence -based care received as well as clinical and functional outcomes . RESULTS Poor subjects were more severely ill  at baseline , with more medical and psychiatric comorbidity . The increases in the amount of evidence -based care and reductions in clinical symptoms and disability were comparable in the two groups such that poorer individuals , although responding equivalently , continued to be more ill and disabled at 12 months . CONCLUSIONS The comparable response of poor individuals in this study suggests that st and ard CBT and pharmacotherapy treatments for panic disorder do not need to be " tailored " to be effective in poor population s. However , the more severe illness both at baseline and follow-up in these poor individuals suggests that treatment programs may need to be extended in order to treat residual symptoms and disability in these patients so that they might achieve comparable levels of remission PURPOSE To revise the 2003 version of the American Urological Association 's ( AUA ) Guideline on the management of benign prostatic hyperplasia ( BPH ) . MATERIAL S AND METHODS From MEDLINE ® search es of English language publications ( January 1999 through February 2008 ) using relevant MeSH terms , articles concerning the management of the index patient , a male ≥45 years of age who is consulting a healthcare provider for lower urinary tract symptoms ( LUTS ) were identified . Qualitative analysis of the evidence was performed . Selected studies were stratified by design , comparator , follow-up interval , and intensity of intervention , and meta-analyses ( quantitative synthesis ) of outcomes of r and omized controlled trials were planned . Guideline statements were drafted by an appointed expert Panel based on the evidence . RESULTS The studies varied as to patient selection ; r and omization ; blinding mechanism ; run-in periods ; patient demographics , comorbidities , prostate characteristics and symptoms ; drug doses ; other intervention characteristics ; comparators ; rigor and intervals of follow-up ; trial duration and timing ; suspected lack of applicability to current US practice ; and techniques of outcomes measurement . These variations affected the quality of the evidence review ed making formal meta- analysis impractical or futile . Instead , the Panel and extractors review ed the data in a systematic fashion and without statistical rigor . Diagnosis and treatment algorithms were adopted from the 2005 International Consultation of Urologic Diseases . Guideline statements concerning pharmacotherapies , watchful waiting , surgical options and minimally invasive procedures were either up date d or newly drafted , peer review ed and approved by AUA Board of Directors . CONCLUSIONS New pharmacotherapies and technologies have emerged which have impacted treatment algorithms . The management of LUTS/BPH continues to evolve BACKGROUND There is a paucity of data to support " next-step " treatments for the many patients with anxiety disorders who remain symptomatic after initial pharmacotherapy . METHOD Thirty patients with a primary diagnosis of an anxiety disorder-panic disorder ( PD ) , social anxiety disorder ( SAD ) , or generalized anxiety disorder (GAD)-refractory to initial pharmacotherapy with an adequate ( or maximally tolerated ) antidepressant and /or benzodiazepine trial of at least 8 weeks ' duration prior to study initiation received open-label augmentation with  flexibly dosed risperidone for 8 weeks . Participants were diagnosed using the Structured Clinical Interview for DSM-IV . RESULTS Risperidone augmentation at a mean + /- SD dose of 1.12 + /- 0.68 mg/day ( range , 0.25 - 3.00 mg/day ) result ed in a significant reduction in anxiety symptoms across disorders as measured by the Clinical Global Impressions-Severity of Illness scale and Hamilton Rating Scale for Anxiety ( HAM-A ) scores and for each disorder-specific primary outcome measure-the Panic Disorder Severity Scale , the Liebowitz Social Anxiety Scale , and HAM-A-in the intent-to-treat sample . Seventy percent ( 21/30 ) of participants completed the 8-week trial , with premature discontinuation due primarily to sedation and weight gain . CONCLUSIONS Although conclusions are limited by the open-label , relatively brief nature of this trial , our data suggest that augmentation with low-dose risperidone may be a useful option for patients with PD , SAD , or GAD refractory to adequate initial intervention with antidepressants and /or benzodiazepines . Longer-term , controlled safety and efficacy data are needed to underst and the place of risperidone augmentation in the algorithm of treatment options for refractory anxiety disorders BACKGROUND More data are needed to guide next-step interventions for panic disorder refractory to initial intervention . METHOD This 24-week r and omized clinical trial ( RCT ) enrolled 46 patients with DSM-IV-defined panic disorder from November 2000 to April 2005 and consisted of 3 phases . Patients who failed to meet remission criteria were eligible for r and omization in the next treatment phase . Phase 1 was a 6-week lead-in with open-label sertraline flexibly dosed to 100 mg ( or escitalopram equivalent ) to prospect ively define treatment refractoriness ( lack of remission ) . Phase 2 was a 6-week double-blind RCT of ( 1 ) increased-dose selective serotonin reuptake inhibitor ( SSRI ) versus ( 2 ) continued SSRI plus placebo . Phase 3 was a 12-week RCT of added cognitive-behavioral therapy ( CBT ) compared to " medication optimization " with SSRI plus clonazepam . Primary endpoints were remission and change in Panic Disorder Severity Scale ( PDSS ) score in the intent-to-treat sample in each phase . RESULTS In phase 1 , 20.5 % ( 8/39 ) of the patients achieved remission , and only baseline severity predicted endpoint PDSS score ( beta [ SE ] = 1.04 [ 0.15 ] , t = 6.76 , P < .001 ) . In phase 2 , increasing the SSRI dose did not result in greater improvement or remission rates  ( placebo 15 % [ n = 2 ] vs increased dose 9 % [ n = 1 ] : Fisher exact test P = NS ) . In phase 3 , remission was minimal ( medication optimization = 11 % [ n = 1 ] ; CBT = 10 % [ n = 1 ] ) , with a lack of group difference in PDSS score reduction ( t(17 ) = 0.51 , P > .60 ) consistent with a small effect size ( d = 0.24 ) . CONCLUSIONS Although power was limited and larger studies are needed , we failed to find evidence for greater benefit of increased SSRI dose versus continuation of current dose for panic disorder symptomatic after 6 weeks at moderate dose . Further , augmentation with CBT or medication optimization with clonazepam augmentation in nonremitted panic after 12 weeks of an SSRI did not differ , suggesting that both are reasonable next-step options . However , low overall remission rates in this comorbid refractory population suggest that better predictors of response to specific treatments over time and additional interventions are needed . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00118417 Non-response to pharmacotherapy for panic disorder ( PD ) is a well-documented problem . However , little information exists to guide next-step strategies for these non-responders . In addition to pharmacologic augmentation strategies , several studies support the efficacy of cognitive-behavior therapy ( CBT ) for these patients , although data on long-term outcomes has been lacking . In this study , we provide one-year outcomes on a sample of 63 patients who completed group CBT for PD after failing to respond adequately to previous pharmacotherapy . Sustained significant benefit was found for all dimensional outcome scores , and nearly two-thirds of the sample met remission criteria . This occurred with reductions in medication use over the follow-up period . Negative predictors of remission status included comorbid dysthymia , social phobia , and generalized anxiety disorder . These results provide additional evidence for the efficacy of CBT for medication non-responders with PD BACKGROUND Effectiveness studies have tested interventions to improve quality of care for depression in primary care , but none , to our knowledge , have been completed for panic disorder ( PD ) in this setting . This study sought to test the clinical effectiveness of PD pharmacotherapy embedded in a disease management framework of " collaborative care " ( CC ) . METHODS One hundred fifteen patients with PD from 3 primary care clinics were r and omized to CC or " usual care " ( UC ) . Patients in CC ( n = 57 ) received educational videotapes and pamphlets ; pharmacotherapy with the selective serotonin reuptake inhibitor paroxetine ; 2 psychiatrist visits and 2 telephone calls in the first 8 weeks ; and up to 5 telephone calls between 3 and 12 months ' follow-up . Usual care patients ( n = 58 ) were treated by their primary care physician . Telephone assessment s of panic , anxiety sensitivity , depression , and disability variables were performed at 3 , 6 , 9 , and 12 months ' follow-up . Adequacy of pharmacotherapy was assessed with an algorithm based on a review of efficacy studies . RESULTS Patients in CC were more likely to receive adequate ( type , dose , duration ) medication and more likely to adhere to this medication at 3 and 6 months . R and om regression analyses showed that CC patients improved significantly more over time compared with UC patients on anxiety , depression , and disability measures , with the greatest effects at 3 and 6 months . CONCLUSIONS Compared with UC , CC interventions significantly improved both quality of care and clinical and functional outcomes in primary care PD patients . Clinical differences were greatest in the first 6 months , corresponding to the greater quality of care and the greater intensity of intervention Panic disorder with or without agoraphobia is a common , often chronic and refractory anxiety disorder . Although a number of pharmacotherapies are now indicated for panic disorder , many patients do not respond to available interventions . We hypothesized that duloxetine , a serotonin‐norepinephrine reuptake inhibitor ( SNRI ) that has greater initial noradrenergic effects than venlafaxine , would have broad efficacy for individuals with panic disorder . Fifteen individuals with panic disorder with or without agoraphobia received 8 weeks of open label duloxetine flexibly dosed from 60 to 120 mg per day . Duloxetine treatment result ed in significant anxiolysis as measured by the primary outcome measure , the Panic Disorder Severity Scale ( PDSS ) ( paired t(df ) = 4.02(14 ) , P= 0.0013 ) , as well as measures of generalized anxiety , depression and quality of life ( all P < 0.05 ) . Although definitive conclusions are limited due to its small open‐label nature , this first prospect i ve study provides preliminary support for the efficacy of duloxetine for panic disorder and suggests larger r and omized controlled study is warranted Introduction Pharmacotherapy and cognitive behavioural therapy ( CBT ) are consistently effective as first-line treatments for  social anxiety disorders ( SADs ) . Nevertheless , pharmacotherapy is often the first choice in clinical practice . In many countries , the first line of pharmacotherapy involves the administration of a selective serotonin reuptake inhibitor ( SSRI ) . Although a significant proportion of patients with SAD fail to respond to the initial SSRI administration , there is no st and ard approach to the management of SSRI-resistant SAD . This paper describes the study protocol for a r and omised controlled trial to evaluate the clinical effectiveness of CBT as a next-step strategy , concomitant with conventional treatment , for patients with SSRI-resistant SAD . Methods and analysis This Prospect i ve R and omized Open Blinded End-point study is design ed with two parallel groups , with dynamic allocation at the individual level . The interventions for the two groups are conventional treatment , alone , and CBT combined with conventional treatment , for 16 weeks . The primary end-point of SAD severity will be assessed by an independent assessor using the Liebowitz Social Anxiety Scale , and secondary end-points include severity of other social anxieties , depressive severity and functional impairment . All measures will be assessed at weeks 0 ( baseline ) , 8 ( halfway point ) and 16 ( postintervention ) and the outcomes will be analysed based on the intent-to-treat . Statistical analyses are planned for the study design stage so that field material s can be appropriately design ed . Ethics and dissemination This study will be conducted at the academic outpatient clinic of Chiba University Hospital . Ethics approval was granted by the Institutional Review Board of Chiba University Hospital . All participants will be required to provide written informed consent . The trial will be implemented and reported in accordance with the recommendations of CONSORT . Clinical Trial Registration Number UMIN000007552 BACKGROUND Panic disorder is a prevalent , often disabling condition among patients in the primary care setting . Although numerous studies have assessed the effectiveness of treatments for depression in primary care , few such studies have been conducted for panic disorder . OBJECTIVE To implement and test the effectiveness of a combined pharmacotherapy and cognitive-behavioral intervention for panic disorder tailored to the primary care setting . DESIGN R and omized , controlled study comparing intervention to treatment as usual . SETTING Six primary care clinics associated with 3 university medical schools , serving an ethnically and socioeconomically diverse patient population . PARTICIPANTS Two hundred thirty-two primary care patients meeting DSM-IV criteria for panic disorder . Comorbid mental and physical disorders were permitted , provided these did not contraindicate the treatment to be provided and were not acutely life threatening . INTERVENTION Patients were r and omized to receive either treatment as usual or an intervention consisting of a combination of up to 6 sessions ( across 12 weeks ) of cognitive-behavioral therapy ( CBT ) modified for the primary care setting , with up to 6 follow-up telephone contacts during the next 9 months , and algorithm-based pharmacotherapy provided by the primary care physician with guidance from a psychiatrist . Behavioral health specialists , the majority inexperienced in CBT for panic disorder , were trained to deliver the CBT and coordinated overall care , including pharmacotherapy . MAIN OUTCOMES MEASURES Proportion of subjects remitted ( no panic attacks in the past month , minimal anticipatory anxiety , and agoraphobia subscale score < 10 on Fear Question naire ) and responding ( Anxiety Sensitivity Index score < 20 ) and change over time in World Health Organization Disability Scale and short form 12 scores . RESULTS The combined cognitive-behavioral and pharmacotherapeutic intervention result ed in sustained and gradually increasing improvement relative to treatment as usual , with significantly higher rates at all points of both the proportion of subjects remitted ( 3 months , 20 % vs 12 % ; 12 months , 29 % vs 16 % ) and responding ( 3 months , 46 % vs 27 % ; 12 months , 63 % vs 38 % ) and significantly greater improvements in World Health Organization Disability Scale ( all points ) and short form 12 mental health functioning ( 3 and 6 months ) scores . These effects were obtained in spite of similar rates of delivery of guideline -concordant pharmacotherapy to the 2 groups . CONCLUSION Delivery of evidence -based CBT and medication using the collaborative care model and a CBT-naive , midlevel behavioral health specialist is feasible and significantly more effective than usual care for primary care panic disorder 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 The relative effectiveness of the available treatments for panic disorder may best be understood in the context of the longitudinal course of the disorder . This study examines a number of clinical ly relevant issues , including long-term outcome after acute treatment , the proportion of patients remaining on single-agent treatment or requiring multiple medications or nonpharmacologic interventions over time , evidence for dose escalation during maintenance high-potency benzodiazepine therapy , and predictors of acute and long-term response to treatment . Fifty-nine panic disorder patients originally r and omized to treatment in a controlled trial comparing alprazolam , clonazepam , and placebo  were reevaluated in a follow-up study . At a mean follow-up of 1.5 years , 78 % of patients remained on medication and the mean dosage of  alprazolam and clonazepam did not increase . Our data suggest that most patients maintain benefit with long-term pharmacotherapy but that residual symptomatology may require more intensive or additional treatment strategies . Response at the endpoint of the acute trial was significantly associated with pretrial baseline Clinical Global Impression Scale score and the presence of dysthymia . Poor outcome at follow-up was associated with total duration of the disorder , agoraphobic subtype , and the presence of comorbid social phobia . We underscore the potential importance of comorbid affective and anxiety disorders as well as phobic patterns in determining long-term response to treatment Social phobia ( social anxiety disorder ) is a highly prevalent and chronic disorder that is associated with significant comorbidity and disability . Despite recent advances in the pharmacotherapy of the disorder , there is a paucity of r and omized controlled trials on patients with comorbid disorders and on maintenance treatment . A r and omized placebo-controlled , double-blind multi-site trial of moclobemide , a reversible inhibitor of monoamine oxidase A , was undertaken with 390 subjects . After an initial 12 weeks , there was the option of continuing for an additional 6 months of treatment . The primary efficacy parameter chosen was responder status as defined by the Clinical Global Impression scale change item . From week 4 onwards , there was a significantly higher response rate on moclobemide than on placebo .  Superiority of medication over placebo was similar in patients with comorbid anxiety disorders ( 33 % of subjects ) and without , as well as in patients with different subtypes of social anxiety disorder ; indeed , treatment with moclobemide rather than placebo was the strongest predictor of response . Adverse events were similar across treatment groups , and were typically mild and transient . In the extension phase , response rates remained higher in the moclobemide group , and ratings of tolerability were equally high in both groups . Thus , in a large sample of social anxiety disorder patients with and without comorbid anxiety disorders , moclobemide was both effective and well-tolerated in the short as well as long-term . These data confirm and extend previous findings on the value of moclobemide in the treatment of social anxiety disorder , and strengthen the range of therapeutic options for managing this important disorder BACKGROUND Cognitive behavioral therapy ( CBT ) and pharmacotherapy are efficacious for the short-term treatment of panic disorder . Less is known about the efficacy of these therapies for individuals who do not respond fully to short-term CBT .  METHOD The current trial is a second-step stratified r and omized design comparing two treatment conditions-selective serotonin reuptake inhibitor ( SSRI ; paroxetine or citalopram ; n = 34 ) and continued CBT  ( n = 24)-in a sample of individuals classified as treatment nonresponders to an initial course of CBT for panic disorder . Participants were r and omized to 3 months of treatment and then followed for an additional 9 months . Only treatment responders after 3 months were maintained on the treatment until 12-month follow-up . Data analysis focused on panic disorder symptoms and achievement of response status across the first 3 months of treatment . Final follow-up data are presented descriptively . RESULTS Participants in the SSRI condition showed significantly lower panic disorder symptoms as compared to continued CBT at 3 months . Results were similar when excluding individuals with comorbid major depression or analyzing the entire intent-to-treat sample . Group differences disappeared during 9-month naturalistic follow-up , although there was significant attrition and use of non study therapies in both arms . CONCLUSIONS These data suggest greater improvement in panic disorder symptoms when switching to SSRI after failure to fully respond to an initial course of CBT . Future studies should further investigate relapse following treatment discontinuation for nonresponders who became responders . Clinical trials.gov Identifier : NCT00000368 ; https:// clinical trials.gov/show/NCT00000368 Background This naturalistic open label follow-up study had three objectives :1 ) To observe the course of illness in Panic Disorder patients receiving long-term versus intermediate-term paroxetine treatment2 ) To compare the relapse rates and side-effect profile after long-term paroxetine treatment between patients with Panic Disorder and Panic Disorder with Agoraphobia.3 ) To observe paroxetine 's  tolerability over a 24 month period . Methods 143 patients with panic disorder ( PD ) , with or without agoraphobia , successfully finished a short-term ( ie 12 week ) trial of paroxetine treatment . All patients then continued to receive paroxetine maintenance therapy for a total of 12 months . At the end of this period , 72 of the patients chose to discontinue paroxetine pharmacotherapy and agreed to be monitored throughout a one year discontinuation follow-up phase . The remaining 71 patients continued on paroxetine for an additional 12 months and then were monitored , as in the first group , for another year while medication-free . The primary limitation of our study is that the subgroups of patients receiving 12 versus 24 months of maintenance paroxetine therapy were selected according to individual patient preference and therefore were not assigned in a r and omized manner . Results Only 21 of 143 patients ( 14 % ) relapsed during the one year medication discontinuation follow-up phase . There were no significant differences in relapse rates between the patients who received intermediate-term ( up to 12 months ) paroxetine and those who chose the long-term course ( 24 month paroxetine treatment ) . 43 patients ( 30.1 % ) reported sexual dysfunction . The patients exhibited an average weight gain of 5.06 kg . All patients who eventually relapsed demonstrated significantly greater weight increase ( 7.3 kg ) during the treatment phase . Conclusions The extension of paroxetine maintenance treatment from 12 to 24 months did not seem to further decrease the risk of relapse after medication discontinuation . Twenty-four month paroxetine treatment is accompanied by sexual side effects and weight gain similar to those observed in twelve month treatment CONTEXT Anxiety disorders commonly present in primary care , where evidence -based mental health treatments often are unavailable or suboptimally delivered . OBJECTIVE To compare evidence -based treatment for anxiety disorders with usual care ( UC ) in primary care for principal and comorbid generalized anxiety disorder ( GAD ) , panic disorder ( PD ) , social anxiety disorder ( SAD ) , and posttraumatic stress disorder ( PTSD ) . DESIGN A r and omized controlled trial comparing the Coordinated Anxiety Learning and Management ( CALM ) intervention with UC at baseline and at 6- , 12- , and 18-month follow-up assessment s. SETTING Seventeen US primary care clinics . PATIENTS Referred primary care sample , 1004 patients , with principal DSM-IV diagnoses of GAD ( n = 549 ) , PD ( n = 262 ) , SAD ( n = 132 ) , or PTSD ( n = 61 ) ( mean [ SD ] age , 43.7 [ 13.7 ] years ; 70.9 % were female ) . Eighty percent of the participants completed 18-month follow-up . INTERVENTIONS CALM ( cognitive behavior therapy and pharmacotherapy recommendations ) and UC . MAIN OUTCOME MEASURES Generalized Anxiety Disorder Severity Scale , Panic Disorder Severity-Self-report Scale , Social Phobia Inventory , and PTSD Checklist-Civilian Version scores . RESULTS CALM was superior to UC for principal GAD at 6-month ( -1.61 ; 95 % confidence interval [ CI ] , -2.42 to -0.79 ) , 12-month ( -2.34 ; -3.22 to -1.45 ) , and 18-month ( -2.37 ; -3.24 to -1.50 ) , PD at 6-month ( -2.00 ; -3.55 to -0.44 ) and 12-month ( -2.71 ; -4.29 to -1.14 ) , and SAD at 6-month ( -7.05 ; -12.11 to -2.00 ) outcomes . CALM was superior to UC for comorbid SAD at 6-month ( -4.26 ; 95 % CI , -7.96 to -0.56 ) , 12-month ( -8.12 , -11.84 to -4.40 ) , and 18- month ( -6.23 , -9.90 to -2.55 ) outcomes . Effect sizes favored CALM but were not statistically significant for other comorbid disorders . CONCLUSIONS CALM ( cognitive behavior therapy and pharmacotherapy medication recommendations ) is more effective than is UC for principal anxiety disorders and , to a lesser extent , comorbid anxiety disorders that present in primary care BACKGROUND Traditional combination strategies of cognitive-behavior therapy plus pharmacotherapy have met with disappointing results for anxiety disorders . Enhancement of cognitive-behavior therapy with d-cycloserine ( DCS ) pharmacotherapy represents a novel strategy for improving therapeutic learning from cognitive-behavior therapy that remains untested in panic disorder . METHOD This is a r and omized , double-blind , placebo-controlled augmentation trial examining the addition of isolated doses of 50 mg d-cycloserine or pill placebo to brief exposure-based cognitive-behavior therapy .  R and omized participants were 31 out patients meeting DSM-IV criteria for panic disorder with or without agoraphobia , who were offered five sessions of manualized cognitive-behavior therapy emphasizing exposure to feared internal sensations ( interoceptive exposure ) but also including informational , cognitive , and situational exposure interventions . Doses of study drug were administered 1 hour before cognitive-behavior therapy sessions 3 to 5 . The primary outcome measures were the Panic Disorder Severity Scale ( PDSS ) and Clinicians ' Global Impressions of Severity . RESULTS Results indicated large effect sizes for the additive benefit of d-cycloserine augmentation of cognitive-behavior therapy for panic disorder . At posttreatment and 1 month follow-up , participants who received d-cycloserine versus placebo had better outcomes on the PDSS and global severity of disorder and were significantly more likely to have achieved clinical ly significant change status ( 77 % vs. 33 % ) . There were no significant adverse effects associated with DCS administration . CONCLUSIONS This pilot study extends support for the role of d-cycloserine in enhancing therapeutic learning from exposure-based cognitive-behavior therapy and is the first to do so in a protocol emphasizing exposure to feared internal sensations of anxiety in panic disorder OBJECTIVES Depression in older patients contributes to personal suffering and family disruption and increases disability , medical morbidity , mortality , suicide risk , and healthcare utilization . The majority of clinical trials of antidepressant treatments are conducted in younger patients . For this reason , clinicians often have to extrapolate from studies in population s that do not present the same problems as older patients . For example , older patients often have serious coexisting medical conditions that may contribute to the depression and complicate the choice of treatment . Older patients as a rule need to be on many medications , some of which may contribute to depression and /or interact with antidepressants . Finally , older adults metabolize medications slowly and are more sensitive to side effects than younger patients . Because of these complexities , we conducted a consensus survey of expert opinion on the pharmacotherapy of depressive disorders in older patients to address clinical questions not definitively answered in the research literature . METHOD After review ing the literature and convening a work group of experts , we prepared a written survey with 64 questions that asked about 857 options . 618 of the options were scored using a modified version of the R AND 9-point scale for rating appropriateness of medical decisions . For the other options , the experts were asked to write in answers ( e.g. , average doses ) or to check a box to indicate their preferred answer . We sent the survey to 50 national experts on geriatric depression , all of whom completed it . Consensus on each option was defined as a nonr and om distribution of scores by chi-square " goodness-of-fit " test . We assigned a categorical rank ( first line/preferred choice , second line/alternate choice , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean rating . Guideline tables indicating preferred treatment strategies were then developed for key clinical situations . RESULTS The expert panel reached consensus on 89 % of the options rated on the 9-point scale . The experts stress the importance of identifying coexisting medical conditions that may be contributing to the depression or complicate treatment . For unipolar nonpsychotic major depression , the preferred strategy is an antidepressant ( selective serotonin reuptake inhibitor [ SSRI ] or venlafaxine XR preferred ) plus psychotherapy . For unipolar psychotic major depression , the treatment of choice is an antidepressant ( SSRI or venlafaxine XR ) plus one of the newer atypical antipsychotics . Electroconvulsive therapy is also first line . For dysthymic disorder or persistent milder depression , the experts recommend combining an antidepressant ( SSRIs preferred ) and psychotherapy . If the patient has a comorbid medical condition ( e.g. , hypothyroidism ) that is contributing to the depression , the experts recommend treating both the depression and the medical condition from the outset . The SSRIs were the top-rated antidepressants for all types of depression . Among them , the experts gave the highest ratings for efficacy and tolerability to citalopram and sertraline . Paroxetine was another first-line option , and fluoxetine was rated high second line . The preferred psychotherapy techniques for treating depression in older patients are cognitive-behavioral therapy , supportive psychotherapy , problem-solving psychotherapy , and interpersonal psychotherapy . The experts also give strong support to including appropriate psychosocial interventions ( e.g. , psychoeducation , family counseling , visiting nurse services ) in the treatment program . The majority of experts would continue treatment with antidepressant medication for at least 1 year if a patient has had a single episode of severe unipolar major depression , for 1 - 3 years for a patient who has had 2 such episodes , and for longer than 3 years if there is a history of 3 or more episodes . CONCLUSIONS The experts reached a high level of consensus on the appropriateness of including both antidepressant medication , specifically SSRIs , and nonpharmacological modalities in treatment plans for severe depression . Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines provide direction for addressing common clinical dilemmas in older individuals . They can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions . Nonetheless , the guidelines can not address the complexities involved in the care of each individual patient and can be most helpful in the h and s of experienced clinicians OBJECTIVE Although studies have suggested that comorbid medical illness can affect the outcome of patients with depression , little is known about whether medical illness comorbidity affects treatment outcome in patients with anxiety . METHOD Primary care patients with panic disorder ( n=232 ) , participating in a r and omized collaborative care intervention of CBT and pharmacology  , were divided into those above ( n=125 ) and below ( n=107 ) the median for burden of chronic medical illness and assessed at 3 , 6 , 9 and 12 months . RESULTS Subjects with a greater burden of medical illness were more psychiatrically ill at baseline , with greater anxiety symptom severity , greater disability and more psychiatric comorbidity . The intervention produced significant and similar increases in amount of evidence -based care , and reductions in clinical symptoms and disability that were comparable in the more and less medically ill groups . CONCLUSIONS The comparable response of individuals with more severe medical illness suggests that CBT and pharmacotherapy for panic disorder work equally well regardless of medical illness comorbidity . However , the more severe psychiatric illness both at baseline and follow-up in these same individuals suggest that treatment programs may need to be extended in time to optimize treatment outcome OBJECTIVE : To assess the effect of  physician training  on management of depression . DESIGN : Primary care physicians were r and omly assigned to a depression management intervention that included an educational program . A before- and -after design evaluated physician practice s for patients not enrolled in the intervention trial . SETTING : One hundred nine primary care physicians in 2 health maintenance organizations located in the Midwest and Northwest regions of the United States . PATIENTS / PARTICIPANTS : Computerized pharmacy and visit data from a group of 124,893 patients who received visits or prescriptions from intervention and usual care physicians . INTERVENTIONS : Primary care physicians received education on diagnosis and optimal management of depression over a 3-month training period . Methods of education included small group interactive discussion s , expert demonstrations , role-play , and academic detailing of pharmacotherapy , criteria for urgent psychiatric referrals , and case review s with psychiatric consultants . MEASUREMENTS AND MAIN RESULTS : Pharmacy and visit data provided indicators of physician management of depression : rate of newly diagnosed depression , new prescription of antidepressant medication , and duration of pharmacotherapy . One year after the training period , intervention and usual care physicians did not differ significantly in the rate of new depression diagnosis ( P=.95 ) or new prescription of antidepressant medicines ( P=.10 ) . Meanwhile , patients of intervention physicians did not differ from patients of usual care physicians in adequacy of pharmacotherapy ( P=.53 ) as measured by 12 weeks of continuous antidepressant treatment . CONCLUSIONS : After education on optimal management of depression , intervention physicians did not differ from their usual care colleagues in depression diagnosis or pharmacotherapy PURPOSE We compared 200 U intradetrusor botulinum toxin A vs placebo in women with refractory idiopathic urge incontinence . MATERIAL S AND METHODS This institutional review board approved , multicenter registered trial r and omized women with refractory urge incontinence , detrusor overactivity incontinence and 6 or greater urge incontinence episodes in 3 days to botulinum toxin A or placebo at a 2:1 ratio . Refractory was defined as inadequate symptom control after 2 or more attempts at pharmacotherapy and 1 or more other first line therapies for detrusor overactivity incontinence . The primary outcome measure was time to failure , as evidence d by a Patient Global Impression of Improvement score of 4 or greater at least 2 months after injection , or changes in treatment ( initiation or increase ) at any time after injection . Safety data , including increased post-void residual volume , defined as more than 200 ml irrespective of symptoms , was obtained at specified time points . RESULTS Approximately 60 % of the women who received botulinum toxin A had a clinical response based on the Patient Global Impression of Improvement . The median duration of their responses was 373 days , significantly longer than the 62 days or less for placebo ( p < 0.0001 ) . In the botulinum toxin A group increased post-void residual urine ( 12 of 28 women or 43 % ) and urinary tract infection in those with increased post-void residual urine ( 9 of 12 or 75 % ) exceeded expected ranges . Further injections were stopped after 43 patients were r and omized , including 28 to botulinum toxin A and 15 to placebo . CONCLUSIONS Local injection of 200 U botulinum toxin A was an effective and durable treatment for refractory overactive bladder . However , a transient post-void residual urine increase was experienced in 43 % of patients . Botulinum toxin A for idiopathic overactive bladder is still under investigation Background : The dem and for clinical ly efficacious , safe , patient acceptable , and cost-effective forms of treatment for mental illness is growing . Several studies have demonstrated benefit from yoga in specific psychiatric symptoms and a general sense of well-being . Objective : To systematic ally examine the evidence for efficacy of yoga in the treatment of selected major psychiatric disorders . Methods : Electronic search es of The Cochrane Central Register of Controlled Trials and the st and ard bibliographic data bases , MEDLINE , EMBASE , and PsycINFO , were performed through April 2011 and an up date d in June 2011 using the keywords yoga AND psychiatry OR depression OR anxiety OR schizophrenia OR cognition OR memory OR attention AND r and omized controlled trial ( RCT ) . Studies with yoga as the independent variable and one of the above mentioned terms as the dependent variable were included and exclusion criteria were applied . Results : The search yielded a total of 124 trials , of which 16 met rigorous criteria for the final review . Grade B evidence supporting a potential acute benefit for yoga exists in depression ( four RCTs ) , as an adjunct to pharmacotherapy in schizophrenia ( three RCTs ) , in children with ADHD ( two RCTs ) , and Grade C evidence in sleep complaints ( three RCTs ) . RCTs in cognitive disorders and eating disorders yielded conflicting results . No studies looked at primary prevention , relapse prevention , or comparative effectiveness versus pharmacotherapy . Conclusion : There is emerging evidence from r and omized trials to support popular beliefs about yoga for depression , sleep disorders , and as an augmentation therapy . Limitations of literature include inability to do double-blind studies , multiplicity of comparisons within small studies , and lack of replication . Biomarker and neuroimaging studies , those comparing yoga with st and ard pharmaco- and psychotherapies , and studies of long-term efficacy are needed to fully translate the promise of yoga for enhancing mental health This study investigated the extent to which occasional cannabis use moderated anxiety and depression outcomes in the Collaborative Care for Anxiety and Panic ( CCAP ) study , a combined cognitive-behavioral therapy ( CBT ) and pharmacotherapy r and omized effectiveness trial . Participants were 232 adults from six university-based primary care outpatient clinics in three West Coast cities r and omized to receive either the CCAP intervention or the usual care condition .  Results showed significant ( P<.01 ) evidence of an interaction between treatment group ( CCAP vs. usual care ) and cannabis use status ( monthly vs. less than monthly ) for depressive symptoms , but not for panic disorder or social phobia symptoms ( all P>.05 ) . Monthly cannabis users ' depressive symptoms improved in the CCAP intervention just as much as those who used cannabis less than monthly , whereas monthly users receiving usual care had significantly more depressive symptoms than those using less than monthly . A combined CBT and medication treatment intervention may be a promising approach for the treatment of depression among occasional cannabis users BACKGROUND The long-term use of opioid analgesic drugs to treat chronic non-cancer pain ( CNCP ) is a major component of pain pharmacotherapy . The interpretation of the evidence concerning its efficacy and risks is currently debated . METHODS An interdisciplinary evidence - and consensus-based S3 guideline was up date d on the basis of a systematic literature search ( CENTRAL , Medline , and Scopus data bases , from October 2008 to October 2013 ) ; meta-analyses of r and omized controlled trials ( ≥ 4 weeks ) ; and a consensus procedure , as specified by the AWMF regulations , including 22 medical and psychological societies and 2 patient self-help organizations . RESULTS 119 publications were used to up date the guideline , and 6 systematic review s with meta-analyses were performed . A nominal group process was used to formulate recommendations concerning the indications and contraindications for the treatment of CNCP with opioid analgesics and the manner in which such treatments should be carried out . Opioid analgesics are an option for the short-term treatment ( 4 - 12 weeks ) of chronic pain due to osteoarthritis ( pain intensity , st and ardized mean difference [ SMD ] : -0.22 and -0.26 ) , diabetic polyneuropathy ( SMD -0.74 ) , post-herpetic neuralgia ( SMD -0.58 ) , and chronic low back pain ( SMD : -0.29 and -0.74 ) . Long-term opioid treatment ( ≥ 26 weeks ) for these diseases benefits only about 25 % of patients . For other conditions , either short- or long-term treatment with opioid analgesics should be considered an individual therapeutic trial . Opioid treatment for pain is contraindicated by primary headaches and by any functional or mental disorder of which pain is a leading manifestation . CONCLUSION To minimize the risks of opioid analgesic treatment , physicians must be aware of its contraindications and must regularly reassess its efficacy and side effects . Pharmacotherapy should be combined with other types of treatment UNLABELLED Introduction Recent pharmacotherapy findings from new alcohol reduction programmes could change the paradigm of alcohol-dependence treatment . MATERIAL AND METHOD This study review s the neurobiological background and pharmacotherapy of alcohol-dependence disorder , focusing on opioid receptor antagonists , abstinence-oriented treatment and moderation-oriented treatment . RESULTS 1 . Alcohol-dependence treatment programs show only low to moderate efficacy . 2 . Patients usually show low motivation to sustain abstinence but high motivation to reduce alcohol use . 3 . A treatment program based on continued reduction of drinking and associated with intermittent treatment with naltrexone can be useful for low-severity alcohol-dependent patients . DISCUSSION Although high severity alcohol-dependent patients should stop drinking alcohol , low severity patients may have the option of reducing their alcohol consumption if they take an opioid antagonist medication every day that they decide to drink alcohol . In the short term , the continuing drinking-reduction programmes may reduce the number of drinks per drinking day and in the long term , they may progressively decrease the obsession for drinking , alcohol seeking behavior , and related medical , behavioral and social disorders . To change the paradigm in the treatment of alcohol-dependence disorder there is a need for further r and omized controlled trials in order to assess their efficacy and tolerability BACKGROUND Although panic disorder can be effectively alleviated by drug treatment , the relapse rate is high . By adding brief dynamic psychotherapy focused on the psychosocial vulnerability of patients with panic disorder to an established drug treatment regimen , we hypothesized that this would result in a lower relapse rate after pharmacotherapy . METHODS Patients with panic disorder ( defined by DSM-III-R ) were r and omized to treatment with either clomipramine for 9 months ( n = 20 ) , or clomipramine for 9 months combined with 15 weekly sessions of brief dynamic psychotherapy ( n = 20 ) . Measures of anxiety and depression were collected at intake and at regular intervals . The patients had blind follow-up interviews at 6 , 12 , and 18 months after beginning treatment . RESULTS All patients in both groups became free of panic attacks within 26 weeks of the start of treatment . On termination of pharmacotherapy , the relapse rate was significantly higher in the clomipramine-only group during the follow-up period . There were significantly lower scores for most anxiety measures in the clomipramine plus psychotherapy group at the 9-month follow-up . CONCLUSION The addition of brief dynamic psychotherapy to treatment with clomipramine significantly reduces the relapse rate of panic disorder compared with clomipramine treatment alone BACKGROUND Panic disorder is a prevalent , often disabling , disorder among primary -care patients , but there are large gaps in quality of treatment in primary care . This study describes the incremental cost-effectiveness of a combined cognitive behavioral therapy ( CBT ) and pharmacotherapy intervention for patients with panic disorder versus  usual primary -care treatment . METHOD This r and omized control trial recruited 232 primary -care patients meeting DSM-IV criteria for panic disorder from March 2000 to March 2002 from six primary -care clinics from university-affiliated clinics at the University of Washington ( Seattle ) and University of California ( Los Angeles and San Diego ) . Patients were r and omly assigned to receive either treatment as usual or a combined CBT and pharmacotherapy intervention for panic disorder delivered in primary care by a mental health therapist . Intervention patients had up to six sessions of CBT modified for the primary -care setting in the first 12 weeks , and up to six telephone follow-ups over the next 9 months . The primary outcome variables were total out-patient costs , anxiety-free days ( AFDs ) and quality adjusted life-years ( QALYs ) . RESULTS Relative to usual care , intervention patients experienced 60.4 [ 95 % confidence interval ( CI ) 42.9 - 77.9 ] more AFDs over a 12-month period . Total incremental out-patient costs were 492 US dollars higher ( 95 % CI 236 - 747 US dollars ) in intervention versus usual care patients with a cost per additional AFD of 8.40 US dollars ( 95 % CI 2.80 - 14.0 US dollars ) and a cost per QALY ranging from 14,158 US dollars ( 95 % CI 6,791 - 21,496 US dollars ) to 24,776 US dollars ( 95 % CI 11,885 - 37,618 US dollars ) . The cost per QALY estimate is well within the range of other commonly accepted medical interventions such as statin use and treatment of hypertension . CONCLUSIONS The combined CBT and pharmacotherapy intervention was associated with a robust clinical improvement compared to usual care with a moderate increase in ambulatory costs Rationale More data are needed to guide “ next step ” strategies for patients with generalized anxiety disorder ( GAD ) remaining symptomatic despite initial pharmacotherapy . Objective This study prospect ively examined the relative efficacy of quetiapine versus placebo augmentation for individuals with GAD remaining symptomatic with initial paroxetine CR pharmacotherapy . Material s and methods Adult out patients with GAD were recruited from 2004 to 2007 at two academic centers . Phase 1 consisted of 10 weeks of open-label paroxetine CR flexibly dosed to a maximum of 62.5 mg/day . Those remaining symptomatic ( Hamilton Anxiety Scale [ HAM-A ] ≥ 7 ) at week 10 were r and omized to quetiapine or placebo augmentation flexibly dosed from 25 to 400 mg/day . Results For participants receiving paroxetine CR ( n = 50 ) , there was a significant reduction in HAM-A scores ( baseline mean ± SD = 22.4 ± 4.2 to endpoint mean ± SD = 11.2 ± 6.9 ; paired t = 12.1 , df = 49 , t < 0.0001 ) with 40 % ( n = 20 ) achieving remission . Counter to our hypothesis , we did not find significant benefit for quetiapine augmentation of continued paroxetine CR ( HAM-A reduction mean ± SD = 2.6 ± 5.8 points quetiapine , 0.3 ± 5.5 points placebo ; t = 0.98 , df = 20 , p = n.s . ) in the r and omized sample ( n = 22 ) with relatively minimal additional improvement overall in phase 2 . Conclusions Although conclusions are considered preliminary based on the relatively small sample size , our data do not support the addition of quetiapine to continued paroxetine CR for individuals with GAD who remain symptomatic after 10 weeks of prospect i ve antidepressant pharmacotherapy and suggest that further research examining strategies for GAD refractory to antidepressants is needed BACKGROUND Obesity , a disorder associated with a myriad of comorbidities , is increasing at an alarming rate around the world . Given that pharmacotherapy has limited available options and that bariatric surgery is reserved for those who are morbidly obese or who have significant comorbidities , the most common approach to the treatment of obesity is st and ard behavioral treatment . This approach includes behavior modification related to eating and activity habits . The purpose of this paper is to describe the rationale , design , methods and baseline sample characteristics of a r and omized controlled trial of a behavioral intervention in weight loss management , referred to as the PREFER study . METHODS The PREFER study , using a four-group design , includes : ( 1 ) a r and omization scheme that permits participants to indicate a preferred dietary treatment approach , and ( 2 ) two dietary options , one of which is a lacto-ovo-vegetarian diet that has demonstrated potential for long-term adherence . The intervention ( 32 treatment sessions ) is delivered over 12 months and is followed by a 6-month maintenance phase ; final assessment occurs at 18 months . RESULTS We screened 932 individuals and r and omized 197 to the study : Treatment Preference-Yes ( n=84 ) and Treatment Preference-No ( n=98 ) . To maintain a balance across the four treatment groups , 15 subjects who preferred the st and ard diet had to be discarded from the Treatment Preference-Yes group . Retention at 18 months for the first of three cohorts was 82 % . CONCLUSIONS The PREFER study is a single center study and is the first r and omized controlled trial examining a lacto-ovo-vegetarian diet as part of weight loss treatment . The ethnically diverse sample includes males and females with a body mass index of 27 to 43 . The study has the potential to make a contribution to underst and ing the role of treatment preference and the potential of a lacto-ovo-vegetarian diet for long-term weight loss OBJECTIVE Major depression occurs with generalized anxiety disorder and panic disorder in up to 60 % of psychiatric and primary care patients . This comorbidity has been associated with greater severity of depression , poorer psychosocial functioning , and poorer treatment outcomes in psychiatric sample s. This study examined the clinical outcomes for depressed primary care patients with and without a lifetime anxiety disorder . METHOD A total of 157 primary care patients who met criteria for major depression were r and omly assigned to st and ardized interpersonal psychotherapy or pharmacotherapy with nortriptyline and were assessed at baseline and at 4 and 8 months on severity of depression , psychosocial functioning , and health-related functioning . RESULTS Depressed patients with a comorbid anxiety disorder presented with significantly more psychopathology and tended to prematurely terminate treatment more frequently than patients with major depression alone . Both st and ardized depression-specific treatments were effective for depressed patients with and without a comorbid generalized anxiety disorder , although time to recovery was longer for the former . Patients with lifetime panic disorder showed poor recovery in response to psychotherapy or pharmacotherapy . CONCLUSIONS St and ardized psychotherapy and pharmacotherapy are effective for patients with major depression with and without a generalized anxiety disorder . However , the longer time to recovery for the former group and lack of response to these treatments by patients with lifetime panic disorder suggest that primary care physicians should carefully assess history of anxiety disorder among depressed patients so as to select a proper intervention Synthesizing evidence from r and omized controlled trials of  digital health education  poses some challenges . These include a lack of clear categorization of digital health education in the literature ; constantly evolving concepts , pedagogies , or theories ; and a multitude of methods , features , technologies , or delivery setting s. The Digital Health Education Collaboration was established to evaluate the evidence on digital education in health professions ; inform policymakers , educators , and students ; and ultimately , change the way in which these professionals learn and are taught . The aim of this paper is to present the overarching methodology that we use to synthesize evidence across our digital health education review s and to discuss challenges related to the process . For our research , we followed Cochrane recommendations for the conduct of systematic review s ; all review s are reported according to the PRISMA ( Preferred Reporting Items for Systematic Review s and Meta-Analyses ) guidance . This included assembling experts in various digital health education fields ; identifying gaps in the evidence base ; formulating focused research questions , aims , and outcome measures ; choosing appropriate search terms and data bases ; defining inclusion and exclusion criteria ; running the search es jointly with librarians and information specialists ; managing abstract s ; retrieving full-text versions of papers ; extracting and storing large data sets , critically appraising the quality of studies ; analyzing data ; discussing findings ; drawing meaningful conclusions ; and drafting research papers . The approach used for synthesizing evidence from digital health education trials is commonly regarded as the most rigorous benchmark for conducting systematic review s. Although we acknowledge the presence of certain biases ingrained in the process , we have clearly highlighted and minimized those biases by strictly adhering to scientific rigor , method ological integrity , and st and ard operating procedures . This paper will be a valuable asset for research ers and method ologists undertaking systematic review s in digital health education AIMS To underst and the relations among anxiety disorders and tobacco dependence , withdrawal symptoms , response to smoking cessation pharmacotherapy and ability to quit smoking . DESIGN R and omized placebo-controlled clinical trial . Participants received six 10-minute individual counseling sessions and either : placebo , bupropion SR , nicotine patch , nicotine lozenge , bupropion SR + nicotine lozenge or nicotine patch + nicotine lozenge . SETTING Two urban research sites . PARTICIPANTS Data were collected from 1504 daily smokers ( > 9 cigarettes per day ) who were motivated to quit smoking and did not report current diagnoses of schizophrenia or psychosis or bupropion use . MEASUREMENTS Participants completed baseline assessment s , the Composite International Diagnostic Interview and ecological momentary assessment s for 2 weeks . FINDINGS A structured clinical interview identified participants who ever met criteria for a panic attack ( n = 455 ) , social anxiety ( n = 199 ) or generalized anxiety disorder ( n = 99 ) , and those who qualified for no anxiety diagnosis ( n = 891 ) . Smokers with anxiety disorders reported higher levels of nicotine dependence and pre-quit withdrawal symptoms . Those ever meeting criteria for panic attacks or social anxiety disorder showed greater quit-day negative affect . Smokers ever meeting criteria for anxiety disorders were less likely to be abstinent at 8 weeks and 6 months post-quit and showed no benefit from single-agent or combination-agent pharmacotherapies . CONCLUSIONS Anxiety diagnoses were common among treatment-seeking smokers and were related to increased motivation to smoke , elevated withdrawal , lack of response to pharmacotherapy and impaired ability to quit smoking . These findings could guide treatment assignment algorithms and treatment development for smokers with anxiety diagnoses 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 . There is renewed interest in refined approaches to brain stimulation , particularly for treatment resistant major depressive disorder ( MDD ) . METHODS The CANMAT guidelines are based on a question -answer format to enhance accessibility to clinicians . An evidence -based format was used with up date d systematic review s of the literature and recommendations were grade d according to Level of Evidence using pre-defined criteria . Lines of Treatment were identified based on criteria that included evidence and expert clinical support . This section on " Neurostimulation Therapies " is one of 5 guidelines articles . RESULTS Among the four forms of neurostimulation review ed in this section , electroconvulsive therapy ( ECT ) has the most extensive evidence , spanning seven decades . Repetitive transcranial magnetic ( rTMS ) and vagus nerve stimulation ( VNS ) have been approved to treat depressed adults in both Canada and the United States with a much smaller evidence base . There is also emerging evidence that  deep brain stimulation ( DBS )  is effective for otherwise treatment resistant depression , but this is an investigational approach in 2009 . LIMITATIONS Compared to other modalities for the treatment of MDD , the data based is limited by the relatively small numbers of r and omized controlled trials ( RCTs ) and small sample sizes . CONCLUSIONS There is most evidence to support ECT as a first-line treatment under specific circumstances and rTMS as a second-line treatment . Evidence to support VNS is less robust and DBS remains an investigational treatment Background : Mindfulness‐based cognitive therapy ( MBCT ) has been widely used to treat patients with depressive disorder to prevent relapse . The objective of this study was to examine the effectiveness of newly developed MBCT program as an adjuvant to pharmacotherapy in the treatment of patients with panic disorder or generalized anxiety disorder . Methods : Forty‐six patients with panic disorder or generalized anxiety disorder were assigned to either MBCT or an anxiety disorder education ( ADE ) program for a period of 8 weeks . The Hamilton Anxiety Rating Scale ( HAM‐A ) , Hamilton Depression Rating Scale ( HAM‐D ) , Beck Anxiety Inventory ( BAI ) , Beck Depression Inventory ( BDI ) , and Symptom Checklist‐90‐Revised ( SCL‐90‐R ) were used to assess the patients at 0 week and after the two programs had been running for 2 , 4 , and 8 weeks . Results : The MBCT group demonstrated significantly more improvement than the ADE group according to all anxiety ( HAM‐A , p<0.01 ; BAI , p<0.01 ; anxiety subscale of SCL‐90‐R , p=0.01 ) and depression ( HAM‐D , p<0.01 ; BDI , p<0.01 ; depression subscale of SCL‐90‐R , p<0.01 ) scale scores . The obsessive‐compulsive and phobic subscales of the SCL‐90‐R also showed significantly more improvement in the MBCT group . However , no significant improvement was observed in the MBCT group versus the ADE group in terms of the somatization , interpersonal sensitivity , paranoid ideation , or psychoticism subscale scores of the SCL‐90‐R. Conclusions : MBCT may be effective at relieving anxiety and depressive symptoms in patients with panic disorder or generalized anxiety disorder . However , well‐ design ed , r and omized controlled trials are needed . Depression and Anxiety , 2009 . © 2009 Wiley‐Liss , OBJECTIVE Lifetime rates of  suicide attempts among patients with bipolar I disorder were compared to rates during a 2-year period of intensive treatment with pharmacotherapy and with one of two adjunctive psychosocial interventions . METHOD Subjects entered the study during an acute mood episode . Subjects were treated with primarily lithium pharmacotherapy and with either psychotherapy specific to bipolar disorder , which included help in regularizing daily routines , or nonspecific , intensive clinical management involving regular visits with empathic clinicians . Data on prior suicide attempts were obtained retrospectively from interviews with the NIMH-Life-Chart method . Data on suicide attempts during the clinical trial were collected systematic ally throughout the protocol . RESULTS The rate of suicide attempts  was 1.05 per 100 person-months before patients entered the trial . Patients experienced a threefold reduction in the rate of suicide attempts during the acute treatment phase ( until the patient achieved stabilization , defined by completion of 4 weeks during which the patient had a mean score of < or = 7 on the 17-item Hamilton Depression Rating Scale and < or = 7 on the Bech-Rafaelsen Mania Scale ) and a 17.5-fold reduction during maintenance treatment . Poisson loglinear regression analysis modeling the relationship between the observed rates and the three protocol stages ( pretreatment , acute , and maintenance ) showed that the reductions were significant in the acute and maintenance phases , compared with the pretreatment phase . No patient with one or more suicide attempts before entering the trial attempted suicide during the protocol . CONCLUSIONS A treatment program in a maximally supportive clinical environment can significantly reduce suicidal behavior in high-risk patients with bipolar I disorder A large number of studies suggest that individual characteristics of psychotherapists affect the outcome of  psychosocial treatments  for psychiatric illness , but little work has been done to see if this is also the case for pharmacotherapy . In the context of a multicenter study that compared psychosocial and medication treatments for panic disorder , we assessed whether such characteristics as age of the psychiatrist , number of years of experience , and gender influence the outcome of treatment with the antipanic drug imipramine . Data were examined by multiple and logistic regression analyses for eight psychiatrists who treated a total of 57 patients with panic disorder . More physician experience , measured as years since completing residency , was associated with better response to imipramine on one of two main dichotomous measures ( the Clinical Global Impression-Improvement Scale ) and on six of nine continuous measure rating scales . Associations between psychiatrist age and outcome and between psychiatrist gender and outcome were also present but on fewer measures . Although these are post-hoc analyses that were not planned when the multicenter study was originally design ed and therefore there are limitations in the information available about the psychiatrists ' characteristics , the findings suggest that even in the context of a clinical trial that employs a specific protocol and single medication , physician experience may influence patient outcome . Depression and Anxiety 17:88 - 93 , 2003 OBJECTIVES To determine whether maintenance antidepressant pharmacotherapy and interpersonal psychotherapy sustain gains in health-related quality of life ( HR-QOL ) achieved during short-term treatment in older patients with depression . DESIGN After open combined treatment with paroxetine and interpersonal psychotherapy , responders were r and omly assigned to a two ( paroxetine vs placebo ) by two ( monthly interpersonal psychotherapy vs clinical management ) double-blind , placebo-controlled maintenance trial . HR-QOL outcomes were assessed over 1 year . SETTING University-based clinic . PATIENTS Of the referred sample of 363 persons aged 70 and older with major depression , 210 gave consent , and 195 started acute treatment ; 116 met criteria for recovery , entered maintenance treatment , and were included in this analysis . INTERVENTIONS Paroxetine ; monthly manual-based interpersonal psychotherapy . MEASUREMENTS Overall HR-QOL as measured using the Quality of Well-Being Scale ( QWB ) and six specific HR-QOL domains derived from the Medical Outcomes Study 36-item Short-Form Health Survey ( SF-36 ) subscales . RESULTS All domains of HR-QOL except physical functioning improved with successful acute and continuation treatment . After controlling for any effects of psychotherapy , pharmacotherapy was superior to placebo in preserving overall well-being ( P=.04 , effect size (r)=0.23 ) , social functioning ( P=.02 , r=0.27 ) , and role limitations due to emotional problems ( P=.007 , r=0.30 ) . Interpersonal psychotherapy ( controlling for the effects of pharmacotherapy ) did not preserve HR-QOL better than supportive clinical management . CONCLUSION Maintenance antidepressant pharmacotherapy is superior to placebo in preserving improvements in overall well-being achieved with treatment response in late-life depression . No such benefit was seen with interpersonal psychotherapy BACKGROUND The results from our 1 year placebo-controlled maintenance/discontinuation study in remitted panic disorder with agoraphobia patients confirmed the significant prophylactic effectiveness of imipramine maintenance treatment but suggested that this may be necessary in only 37 % of the patients who relapse following discontinuation of 6 months acute imipramine treatment . This paper presents pilot data from a second year extension of the above-mentioned study with the aim of exploring the putative protective effects of maintenance imipramine therapy beyond the 1st year . METHOD Eighteen patients from the 30 who survived , in stable remission , the first 12 months of the maintenance/discontinuation study gave written consent to participate in a double-blind 2nd year extension phase with the knowledge that those on placebo will continue on the same condition ( N = 7 , PBO-PBO ) and those on imipramine ( N = 11 ) will be rer and omized to 2nd year maintenance ( N = 4 , IMI-IMI ) or placebo substitution ( N = 7 , IMI-PBO ) . The procedures continued unchanged from that of the 1st year of the study and patients were followed with planned assessment s every 2 months over the second 12-month experimental period of the study . RESULTS None of the IMI-IMI patients relapsed , two ( 28.5 % ) of the IMI-PBO patients relapsed , and two ( 28.5 % ) of PBO-PBO patients relapsed . The mean estimated time without relapse was 10 months and 9 months for IMI-PBO and PBO-PBO , respectively . The estimated probability of not relapsing was .64 for IMI-PBO and .60 for PBO-PBO ( Mantel-cox test chi2 = .84 , p = .77 ) . CONCLUSION These interlocking controlled observations tentatively suggest that a substantial degree of prophylactic efficacy continues and that a substantial need for continued prophylaxis exists beyond the 1st year of maintenance imipramine treatment in panic disorder with agoraphobia patients OBJECTIVES Borderline personality disorder ( BPD ) is frequently encountered in both adult and youth population s. There is a robust literature supporting psychotherapy for adults with BPD , but the literature supporting its use for BPD in youth is more limited . METHODS A literature review was conducted using the keywords " borderline personality disorders " and " adolescence . " Relevant articles were review ed for inclusion . RESULTS Several specialized treatments have been studied with mixed results . Dialectical behaviour therapy has no r and omized controlled trials in adolescents ,  emotion regulation training  has not demonstrated superiority of treatment as usual , and  cognitive analytic therapy has demonstrated more rapid recovery but little difference at follow-up .  Mentalization-based treatment  has one study supporting its use in self-harming adolescents . Pharmacotherapy has no evidence supporting its use in this population . CONCLUSIONS Structured therapy may be the most important therapeutic component in this population Patients successfully treated during a 3-month period with either imipramine hydrochloride pharmacotherapy , cognitive therapy , or combined cognitive-pharmacotherapy were monitored during a 2-year posttreatment follow-up period . Half of the patients treated with pharmacotherapy alone continued to receive study medications for the first year of the follow-up . All other patients discontinued treatment at the end of the acute treatment phase . Patients treated with cognitive therapy ( either alone or in combination with medication ) evidence d less than half the rate of relapse shown by patients in the medication -- no continuation condition , and their rate did not differ from that of patients provided with continuation medication . It appears that providing cognitive therapy during acute treatment prevents relapse . Whether this preventive effect extends to recurrence remains to be determined The present study investigated the impact of pre-existing pharmacotherapy regimes on the long-term outcome of brief intensive group cognitive-behavioural therapy ( BIGCBT ) in the treatment of panic disorder with or without agoraphobia in 106 patients ( 74 females ) . Forty patients were allocated to BIGCBT without medication , 40 to BIGCBT plus anti-anxiety medication , 10 to BIGCBT plus anti-depressant medication and 16 to BIGCBT plus combined anti-anxiety and anti-depressant medications . The mean follow-up period was 3.2 yr and ranged from 1.1 to 6.2 yr . The results demonstrated that patients who received BIGCBT concurrent with pre-existing medication regimes did not differ significantly ( P > 0.001 ) from each other or from patients who underwent BIGCBT without medication on any of the dependent measures either at pre-treatment assessment or long-term follow-up . However , BIGCBT ( with or without pharmacotherapy ) was associated with significant ( P < 0.001 ) long-term improvements in frequency of panic attacks , avoidance behaviour and question naire measures of anxiety , depression and agoraphobia . Furthermore , the large majority ( 80 % ) of patients in the BIGCBT without medication group remained medication-free at long-term follow-up . Of those patients who underwent BIGCBT concurrent with pre-existing pharmacotherapy , a large percentage ( 44 % ) reported no longer taking medication for their condition at long-term follow-up . Overall , it is concluded that pre-existing medication regimes ( anti-anxiety , anti-depressant or combinations of these ) do not significantly enhance or detract from the long-term outcome of a BIGCBT program used in the treatment of panic disorder and agoraphobia CONTEXT Mindfulness-based cognitive therapy ( MBCT ) is a group-based psychosocial intervention design ed to enhance self-management of prodromal symptoms associated with depressive relapse . OBJECTIVE To compare rates of relapse in depressed patients in remission receiving MBCT against maintenance antidepressant pharmacotherapy  , the current st and ard of care . DESIGN Patients who met remission criteria after 8 months of algorithm-informed antidepressant treatment were r and omized to receive maintenance antidepressant medication , MBCT , or placebo and were followed up for 18 months . SETTING Outpatient clinics at the Centre for Addiction and Mental Health , Toronto , Ontario , Canada , and St Joseph 's Healthcare , Hamilton , Ontario . PARTICIPANTS One hundred sixty patients aged 18 to 65 years meeting DSM-IV criteria for major depressive disorder with a minimum of 2 past episodes . Of these , 84 achieved remission ( 52.5 % ) and were assigned to 1 of the 3 study conditions . INTERVENTIONS Patients in remission discontinued their antidepressants and attended 8 weekly group sessions of MBCT , continued taking their therapeutic dose of antidepressant medication , or discontinued active medication and were switched to placebo . MAIN OUTCOME MEASURE Relapse was defined as a return , for at least 2 weeks , of symptoms sufficient to meet the criteria for major depression on module A of the Structured Clinical Interview for DSM-IV . RESULTS Intention-to-treat analyses showed a significant interaction between the quality of acute-phase remission and subsequent prevention of relapse in r and omized patients ( P = .03 ) . Among unstable remitters ( 1 or more Hamilton Rating Scale for Depression score > 7 during remission ) , patients in both MBCT and maintenance treatment showed a 73 % decrease in hazard compared with placebo ( P = .03 ) , whereas for stable remitters ( all Hamilton Rating Scale for Depression scores ≤7 during remission ) there were no group differences in survival . CONCLUSIONS For depressed patients achieving stable or unstable clinical remission , MBCT offers protection against relapse/recurrence on a par with that of maintenance antidepressant pharmacotherapy . Our data also highlight the importance of maintaining at least 1 long-term active treatment in unstable remitters Summary The impact of the avoidance behaviour on the psychopharmacological treatment of panic disorder was explored in the Cross National Collaborative Panic Study ( n=1134 patients ) ; in this double blind r and omized trial alprazolam , imipramine and placebo were compared during an 8-week treatment period . Patients with extensive avoidance behaviour ( agoraphobia ) had the most profit from the active drugs . Counter expectancy these specific drug effects were most pronounced in avoidance behaviour . Active drugs ( in particular imipramine ) were especially more effective than placebo if the patients presented with associated avoidance behaviour . The results suggest that agoraphobia defines more a particular type of anxiety disorder overlapping with panic disorder than merely a severe state of panic disorder 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 We explored a causal sequence between panic and avoidance to provide recommendations for psychotherapy , pharmacotherapy , and their combination in treating agoraphobia . We produced a two-way [ ( imipramine hydrochloride vs placebo ] by [ office-based behavioral therapy vs in vivo exposure ] ) design by amalgamating two studies . We assessed agoraphobic patients for panic and avoidance at these time points : baseline ( week 0 ) , midcourse ( week 13 ) , and termination ( week 26 ) . The causal sequence model was tested by path analysis . Imipramine was superior to placebo in lowering panic and avoidance at both postbaseline time points . Exposure was superior to office-based treatment in lowering avoidance only at week 13 . Exposure appeared to produce quicker improvement of avoidance than office-based therapy , but relapse occurred if this improvement was not supported by medication . Exposure did not benefit panic . We believe patients should be informed that imipramine is superior to exposure in inducing a panic-free state . Exposure without imipramine is of benefit only in reducing avoidance , but adding imipramine to exposure is necessary for panic control and substantially improves exposure and exposure maintenance Although serotonin reuptake inhibitors ( SRIs ) are the medications of choice in the treatment of obsessive-compulsive disorder ( OCD ) , only 50 - 60 % of patients respond to a single trial of any of these agents . Improved knowledge of the predictors of response to treatment may have important clinical implication s. Data from a large r and omized placebo-controlled trial of citalopram in OCD was analysed using logistic regression to determine predictors of response . Demographic ( age , sex ) , clinical ( OCD severity and duration , depression severity , prior treatment ) and trial variables  ( citalopram dose , treatment duration ) were included . Subjects with longer duration of OCD , more severe OCD symptoms or previous selective SRI use were less likely to be responders in the citalopram trial . In contrast , subjects who received adequate medication doses for sufficient periods of time in the citalopram trial were more likely to be responders . Despite greater awareness of OCD in recent years , there is evidence that the disorder continues to be underdiagnosed and undertreated . The data here emphasize the crucial importance of early diagnosis and treatment of OCD , and of pharmacotherapy with appropriate dose and duration This clinical guideline provides recommendations for the behavioural and psychosocial interventions ( BPI ) of children and adolescents with tic disorders prepared by a working group of the European Society for the Study of Tourette Syndrome ( ESSTS ) . A systematic literature search was conducted to obtain an up date on the efficacy of BPI for tics . Relevant studies were identified using computerised search es of the Medline and PsycINFO data bases and the Cochrane Library for the years 1950–2010 . The search identified no meta-analyses , yet twelve ( systematic ) review s and eight r and omised controlled trials provided evidence for the current review . Most evidence was found for habit reversal training ( HRT ) and the available but smaller evidence also supports the efficacy of exposure with response prevention ( ERP ) . Both interventions are considered first line behavioural treatments for tics for both children and adults and should be offered to a patient , taking into account his preference . Treatments that are considered second line or add-on behavioural treatments are  contingency management , function based interventions and relaxation training . Neurofeedback is still experimental . Almost no research was identified that examined the efficacy of psychosocial interventions , e.g. , psychoeducation and group work . Based on clinical practice , this guideline recommends behavioural treatment as first line offer to patients in most cases . It should be embedded within a psychoeducational and supportive context and can be combined with drug treatment BACKGROUND : Over the last two decades very few advances have been made in the development of new treatments for obsessive-compulsive disorder ( OCD ) . While patients with OCD improve with available treatments ( pharmacotherapy and /or cognitive-behavioral therapy ) , moderate levels of OCD symptoms often persist even with adequate doses and duration s of these treatments . Building on the growing body of evidence for the efficacy of exercise in the treatment of other psychiatric disorders , interventions to increase aerobic exercise in patients with OCD represent a potentially useful yet relatively unexplored strategy in OCD . METHODS / DESIGN : One hundred and two ( 102 ) patients with clinical ly significant OCD symptoms despite current engagement in recommended treatments ( pharmacotherapy and /or CBT ) will be r and omly assigned to receive either a 12-week moderate intensity aerobic exercise ( AE ) intervention or a health education control ( HEC ) intervention . Follow-up interviews will be conducted at the end of treatment and at 3- , 6- and 12-months post-intervention . They will assess OCD severity , nonspecific anxiety , depression , quality of life , cardiorespiratory fitness and cognition ( executive function ) . DISCUSSION : If efficacy is established , patients with OCD who have clinical ly significant residual symptoms despite current pharmacotherapy or CBT would gain a valuable and practical treatment augmentation option BACKGROUND Psychotherapy of " pure " dysthymic disorder remains understudied . This article reports outcomes of an acute r and omized trial of 94 subjects treated for 16 weeks with either interpersonal psychotherapy ( IPT ) , brief supportive psychotherapy ( BSP ) , sertraline , or sertraline plus IPT .  METHODS Recruited by clinical referral and advertising , subjects met DSM-IV criteria for early onset dysthymic disorder , with no episode of major depression in the prior six months . They were r and omly assigned to one of four 16-week treatments , with options for crossover or continuation treatment . Results were analyzed from the intention-to-treat sample by ANCOVA , controlling for baseline depressive severity . RESULTS Subjects improved in all conditions over time , with the cells including sertraline pharmacotherapy showing superiority over psychotherapy alone for response and remission . Response rates were 58 % for sertraline alone , 57 % for combined treatment , 35 % for IPT , and 31 % for BSP . LIMITATIONS The study was underpowered and may have employed too " active " a control condition . Follow-up data were unobtainable . CONCLUSIONS In this acute trial for " pure " dysthymic disorder , sertraline with or without IPT showed advantages relative to IPT and BSP . Method ological difficulties may have limited differential outcome findings . This study bolsters a small but growing literature on the treatment of dysthymic disorder , suggesting that pharmacotherapy may acutely benefit patients more than psychotherapy Patients with panic disorder ( N = 1168 ) were enrolled in a multicenter , 8-week , double-blind clinical trial of imipramine , alprazolam , and placebo to analyze whether the effectiveness of these agents is dependent on the depressive/dysphoric symptomatology which often coexists in panic disorder patients . In addition to analyses performed on the whole sample of patients , the authors conducted analyses on a sub sample ( N = 312 ) defined by multiple criteria to ensure the absence of depression and dysphoria . In both the overall sample and the nondepressed sub sample , the clinical response to imipramine or alprazolam was found to be independent of the presence of depression or dysphoria . In panic disorder patients for whom pharmacotherapy is being considered as treatment , the absence of depression is apparently not a contraindication Cambodian refugees with posttraumatic stress disorder ( PTSD ) represent a cohort in severe need of treatment , but little information is available to guide treatment choices . We selected a sample of pharmacotherapy-refractory individuals to test the efficacy of combination treatment with sertraline and cognitive-behavior therapy ( CBT ) for treating PTSD . Participants in this pilot study were ten Khmer-speaking women who had been at a mean age of 22 - 26 years during the Pol Pot period ( 1975 - 1979 ) . These patients were r and omly assigned to either sertraline alone or combined treatment . We found that combined treatment offered additional benefit in the range of medium to large effect sizes for PTSD and associated symptoms . Our findings indicate that substantial gains can be achieved by adding CBT to pharmacotherapy for PTSD , and that a program of CBT emphasizing information , exposure , and cognitive-restructuring can be successfully modified for Khmer-speaking refugees CONTEXT Numerous studies have pointed to the failure of prophylaxis with pharmacotherapy alone in the treatment of bipolar I disorder . Recent investigations have demonstrated benefits from the addition of psychoeducation or psychotherapy to pharmacotherapy in this population . OBJECTIVE To compare 2 psychosocial interventions : interpersonal and social rhythm therapy ( IPSRT ) and an intensive clinical management ( ICM ) approach in the treatment of bipolar I disorder . DESIGN R and omized controlled trial involving 4 treatment strategies : acute and maintenance IPSRT ( IPSRT/IPSRT ) , acute and maintenance ICM ( ICM/ICM ) , acute IPSRT followed by maintenance ICM ( IPSRT/ICM ) , or acute ICM followed by maintenance IPSRT ( ICM/IPSRT ) . The preventive maintenance phase lasted 2 years . SETTING Research clinic in a university medical center . PARTICIPANTS One hundred seventy-five acutely ill individuals with bipolar I disorder recruited from inpatient and outpatient setting s , clinical referral , public presentations about bipolar disorder , and other public information activities . INTERVENTIONS Interpersonal and social rhythm therapy , an adaptation of Klerman and Weissman 's interpersonal psychotherapy to which a social rhythm regulation component has been added , and ICM . MAIN OUTCOME MEASURES Time to stabilization in the acute phase and time to recurrence in the maintenance phase . RESULTS We observed no difference between the treatment strategies in time to stabilization . After controlling for covariates of survival time , we found that participants assigned to IPSRT in the acute treatment phase survived longer without a new affective episode ( P = .01 ) , irrespective of maintenance treatment assignment . Participants in the IPSRT group had higher regularity of social rhythms at the end of acute treatment ( P<.001 ) . Ability to increase regularity of social rhythms during acute treatment was associated with reduced likelihood of recurrence during the maintenance phase ( P = .05 ) . CONCLUSION Interpersonal and social rhythm therapy appears to add to the clinical armamentarium for the management of bipolar I disorder , particularly with respect to prophylaxis of new episodes BACKGROUND Irritable bowel syndrome ( IBS ) is a chronic debilitating functional gastrointestinal disorder . Diet and lifestyle changes are important management strategies . The aim of these guidelines is to systematic ally review key aspects of the dietary management of IBS , with the aim of providing evidence -based guidelines for use by registered dietitians . METHODS Questions relating to diet and IBS symptom management were developed by a guideline development group . These included the role of milk and lactose , nonstarch polysaccharides ( NSP ) , fermentable carbohydrates in abdominal bloating , probiotics and empirical or elimination diets . A comprehensive literature search was conducted and relevant studies from January 1985 to November 2009 were identified using the electronic data base search engines : Cinahl , Cochrane Library , Embase , Medline , Scopus and Web of Science . Evidence statements , recommendations , good practice points and research recommendations were developed . RESULTS Thirty studies were critically appraised . A dietetic care pathway was produced following a logical sequence of treatment and formed the basis of these guidelines . Three lines of dietary management were identified . first line :  Clinical and dietary assessment , healthy eating and lifestyle management  with some general advice on lactose and NSP . Second line : Advanced dietary interventions to improve symptoms based on NSP , fermentable carbohydrates and probiotics . Third line : Elimination and empirical diets . Research recommendations were also identified relating to the need for adequately powered and well design ed r and omised controlled trials . CONCLUSIONS These guidelines provide evidence -based details of how to achieve the successful dietary management of IBS BACKGROUND AND OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are currently the first-line treatment for panic disorder , although up to 30 % of patients either do not respond to SSRIs or withdraw due to adverse events . Reboxetine , a selective norepinephrine reuptake inhibitor ( selective NRI ) , is effective in treating depression and may alleviate depression-related anxiety . This study aim ed to investigate the efficacy of reboxetine in the treatment of patients with panic disorder who did not respond to SSRIs . METHOD In this 6-week , open-label study , 29 adult out patients with panic disorder who had previously failed to respond to SSRI treatment received reboxetine 2 mg/day , titrated to a maximum of 8 mg/day over the first 10 days .  Efficacy was assessed using the Panic Self- Question naire ( PSQ ) , the Hamilton Rating Scale for Anxiety ( HAM-A ) , the 17-item Hamilton Rating Scale for Depression ( HRSD ) and the Global Assessment of Functioning ( GAF ) Scale . RESULTS The 24 patients who completed the study responded well to reboxetine treatment . Significant improvement ( p < 0.001 ) was observed in the number of daily panic attacks , and on the scales measuring anxiety , depression and functioning . Reboxetine was generally well tolerated . Five patients withdrew due to  adverse events . CONCLUSIONS Reboxetine appears to be effective in the treatment of SSRI-refractory panic disorder patients and warrants further clinical investigation OBJECTIVE The purpose of this study was to evaluate the outcome of bipolar disorder in the context of maintenance pharmacotherapy . METHOD Eighty-two bipolar out patients were followed prospect ively for a mean of 4.3 years ( minimum of 2 years ) ; symptom rating and psychosocial outcome scales were used , and pharmacotherapy was rated on a 5-point scale . RESULTS Despite continual maintenance treatment , survival analysis indicated a 5-year risk of relapse into mania or depression of 73 % . Of those who relapsed , two-thirds had multiple relapses . Relapse could not be attributed to inadequate medication . Even for those who did not relapse , considerable affective morbidity was observed . A measure of cumulative affective morbidity appeared to be a more sensitive correlate of psychosocial functioning than was the number of relapses . Poor psychosocial outcome paralleled poor syndromal course . Poor psychosocial functioning , especially occupational disruption , predicted a shorter time to relapse . Depressions were most strongly related to social and family dysfunction . CONCLUSIONS Even aggressive pharmacological maintenance treatment does not prevent relatively poor outcome in a significant number of bipolar patients OBJECTIVE To provide up date d , evidence -based recommendations for the prevention and management of hypertension in adults . OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions , evidence was review ed from r and omized controlled trials and systematic review s of trials . Changes in cardiovascular morbidity and mortality were the primary outcomes of interest . However , for lifestyle interventions , blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field . For treatment of patients with kidney disease , the progression of kidney dysfunction was also accepted as a clinical ly relevant primary outcome . EVIDENCE A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to up date the 2006 Canadian Hypertension Education Program recommendations . In addition , reference lists were scanned and experts were contacted to identify additional published studies . All relevant articles were review ed and appraised independently by both content and method ological experts using prespecified levels of evidence . RECOMMENDATIONS Dietary lifestyle modifications for prevention of hypertension , in addition to a well-balanced diet , include a dietary sodium intake of less than 100 mmol/day . In hypertensive patients , the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day . Other lifestyle modifications for both normotensive and hypertensive patients include : performing 30 min to 60 min of aerobic exercise four to seven days per week ; maintaining a healthy body weight ( body mass index of 18.5 kg/m2 to 24.9 kg/m2 ) and waist circumference ( less than 102 cm in men and less than 88 cm in women ) ; limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women ; following a diet reduced in saturated fat and cholesterol , and one that emphasizes fruits , vegetables and low-fat dairy products , dietary and soluble fibre , whole grains and protein from plant sources ; and considering stress management in selected individuals with hypertension . For the pharmacological management of hypertension , treatment thresholds and targets should take into account each individual 's global atherosclerotic risk , target organ damage and any comorbid conditions : blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease . Most patients require more than one agent to achieve these blood pressure targets . In adults without compelling indications for other agents , initial therapy should include thiazide diuretics ; other agents appropriate for first-line therapy for diastolic and /or systolic hypertension include angiotensin-converting enzyme ( ACE ) inhibitors ( except in black patients ) , long-acting calcium channel blockers ( CCBs ) , angiotensin receptor blockers ( ARBs ) or beta-blockers ( in those younger than 60 years of age ) . First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs . Certain comorbid conditions provide compelling indications for first-line use of other agents : in patients with angina , recent myocardial infa rct ion , or heart failure , beta-blockers and ACE inhibitors are recommended as first-line therapy ; in patients with cerebrovascular disease , an ACE inhibitor plus diuretic combination is preferred ; in patients with nondiabetic chronic kidney disease , ACE inhibitors are recommended ; and in patients with diabetes mellitus , ACE inhibitors or ARBs ( or , in patients without albuminuria , thiazides or dihydropyridine CCBs ) are appropriate first-line therapies . All hypertensive patients with dyslipidemia should be treated using the thresholds , targets and agents outlined in the Canadian Cardiovascular Society position statement ( recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease ) . Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy . Once blood pressure is controlled , acetylsalicylic acid therapy should be considered . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence -Based Recommendations Task Force . All recommendations reported here achieved at least 95 % consensus . These guidelines will continue to be up date d annually The authors examined weight change in 32 elderly patients treated for 12 weeks with either nortriptyline or paroxetine during acute-phase pharmacotherapy .  R and om assignment to treatment and double-blind assessment of weight change were performed , including ascertainment of premorbid ( i.e. , pre-depression ) weight . Pretreatment severity of depression was correlated with weight loss during the depressive episode and depression-related weight loss , in turn , correlated with weight regained during antidepressant treatment . There was no differential weight change associated with nortriptyline vs. paroxetine . Rather , subjects in both groups approximated their premorbid weights by 12 weeks of acute-phase pharmacotherapy with either agent . However , additional investigation of weight change during continuation and maintenance pharmacotherapy is necessary and would be clinical ly useful for the long-term management of elderly patients with depression The present study examined the efficacy of an 8-wk , cognitive-behavioral group treatment for panic disorder . Patients meeting DSM-III-R criteria for panic disorder with or without agoraphobia were r and omly assigned to treatment ( N = 34 ) or delayed treatment control ( N = 33 ) . The treatment consisted of : ( a ) education and corrective information ; ( b ) cognitive therapy ; ( c ) training in diaphragmatic breathing ; and ( d ) interoceptive exposure . At posttreatment , 85 % of treated Ss were panic free , compared to 30 % of controls . Treated Ss also showed clinical ly significant improvement on indices of anxiety , agoraphobia , depression and fear of fear . Recovery , as estimated conservatively by the attainment of normal levels of functioning on each of the major clinical dimensions of the disorder ( i.e. panic , anxiety and avoidance ) , was achieved in 64 % of the treated Ss and 9 % of the controls . At the 6 month follow-up , 63 % of the treated patients met criteria for recovery . These findings mirror those from recently-completed trials of individually-administered cognitive-behavioral treatment , and suggest that CBT is a viable alternative to pharmacotherapy in the treatment of panic disorder Objective There is little r and omized controlled trial ( RCT ) evidence to guide treatment for anxiety after stroke . We systematic ally review ed RCTs of anxiety interventions in acquired brain injury ( ABI ) conditions including stroke and traumatic brain injury ( TBI ) in order to summarize efficacy and key aspects of trial design to help guide future RCTs . Methods We search ed the Cochrane trial register , Medline , Embase , PsychInfo and CINAHL systematic ally up to August 2017 . Two independent review ers systematic ally selected studies and extracted data . We summarized the effect size , key study characteristics and sources of potential bias in trial design . Results 14 studies ( 12 stroke ; one stroke & TBI ; one TBI ) with 928 participants were included . Meta- analysis of five psychotherapy comparisons favoured intervention over control ( st and ardized mean difference ( SMD ) : − 0.41 [ − 0.79 , − 0.03 ] , I2 = 28 % ) ; Overall effect size of pharmacotherapy comparisons favoured intervention over control ( SMD : − 2.12 [ − 3.05 , − 1.18 ] , I2 = 89 % ) . One comparison of mixed pharmacotherapy and psychotherapy favoured intervention over usual care ( SMD : − 4.79 [ − 5.87 , − 3.71 ] ) . One comparison favoured  forest therapy versus urban control ( SMD : − 2.00 [ − 2.59 , − 1.41 ] ) . All positive studies carried high or unclear risk of bias . Sample sizes were small in all included studies . Conclusions There is low quality evidence to suggest that psychotherapy and pharmacotherapy may be effective interventions in the treatment of anxiety after stroke based on underpowered studies that carried high risk of bias . Large-scale well- design ed definitive trials are needed to establish whether pharmacological or psychotherapy works . Our review highlighted key considerations for investigators wishing to design high quality trials to evaluate treatments for anxiety after stroke BACKGROUND Bipolar patients are at risk for relapses of their illness even when undergoing optimal pharmacotherapy . This study was performed to determine whether combining family-focused therapy ( FFT ) with pharmacotherapy during a postepisode interval enhances patients ' mood stability during maintenance treatment . METHODS In a r and omized controlled trial , 101 bipolar patients were assigned to FFT and pharmacotherapy or a less intensive crisis management ( CM ) intervention and pharmacotherapy . Outcome assessment s were conducted every 3 to 6 months for 2 years . Participants ( mean + /- SD age , 35.6 + /- 10.2 years ) were referred from inpatient or outpatient clinics after onset of a manic , mixed , or depressed episode .  FFT consisted of 21 sessions of psychoeducation , communication training , and problem-solving skills training . Crisis management consisted of 2 sessions of family education plus crisis intervention sessions as needed . Both protocol s lasted 9 months . Patients received pharmacotherapy for 2 study years . Main outcome measures included time to relapse , depressive and manic symptoms , and medication adherence . RESULTS Rates of study completion did not differ across the FFT ( 22/31 , 71 % ) and CM groups ( 43/70 , 61 % ) . Patients undergoing FFT had fewer relapses ( 11/31 , 35 % ) and longer survival intervals ( mean + /- SD , 73.5 + /- 28.8 weeks ) than patients undergoing CM ( 38/70 , 54 % ; mean + /- SD , 53.2 + /- 39.6 weeks ; hazard ratio , 0.38 ; 95 % confidence interval , 0.20 - 0.75 ; P = .003 ; intent to treat ) . Patients undergoing FFT showed greater reductions in mood disorder symptoms and better medication adherence during the 2 years than patients undergoing CM . CONCLUSION Combining family psychoeducation with pharmacotherapy enhances the postepisode symptomatic adjustment and drug adherence of bipolar patients This paper reports on the development and initial psychometric evaluation of the Treatment Adherence Survey-patient version ( TAS-P ) , a brief instrument design ed to assess patient adherence to Cognitive-Behavioral Therapy ( CBT ) and pharmacotherapy recommendations for OCD . Eighty individuals with Obsessive Compulsive Disorder ( OCD ) were administered the TAS-P as part of the intake interview of a prospect i ve , observational study of the course of OCD . Results demonstrated excellent test-retest reliability . Responses on the TAS-P were also significantly correlated with scores on a self-report measure of general treatment adherence and with data collected from a chart- review , demonstrating concurrent validity . Treatment adherence was not explained by demographic variables . However , participants who reported nonadherence to CBT recommendations had more severe OCD symptoms at the time of intake than those who did not endorse CBT nonadherence ( mean Y-BOCS = 23.27 + /- 7.5 versus 18.20 + /- 8.0 , respectively ) . Results suggest that the TAS-P is a promising instrument for assessing reasons for nonadherence to recommendations for CBT and pharmacotherapy interventions Abstract Objectives . This 2013 up date of the practice guidelines for the biological treatment of unipolar depressive disorders was developed by an international Task Force of the World Federation of Societies of Biological Psychiatry ( WFSBP ) . The goal has been to systematic ally review all available evidence pertaining to the treatment of unipolar depressive disorders , and to produce a series of practice recommendations that are clinical ly and scientifically meaningful based on the available evidence . The guidelines are intended for use by all physicians seeing and treating patients with these conditions . Methods . The 2013 up date was conducted by a systematic up date literature search and appraisal . All recommendations were approved by the Guidelines Task Force . Results . This first part of the guidelines ( Part 1 ) covers disease definition , classification , epidemiology , and course of unipolar depressive disorders , as well as the management of the acute and continuation phase treatment . It is primarily concerned with the biological treatment ( including antidepressants , other psychopharmacological medications , electroconvulsive therapy , light therapy , adjunctive and novel therapeutic strategies ) of adults . Conclusions . To date , there is a variety of evidence -based antidepressant treatment options available . Nevertheless there is still a substantial proportion of patients not achieving full remission . In addition , somatic and psychiatric comorbidities and other special circumstances need to be more thoroughly investigated . Therefore , further high- quality informative r and omized controlled trials are urgently needed OBJECTIVE This study sought to evaluate the effectiveness of compliance therapy in increasing adherence to pharmacological treatment for alcohol dependence . METHOD Forty subjects were r and omly allocated to receive usual medical care ( n = 20 ) or usual medical care plus compliance therapy ( n = 20 ) . All subjects were prescribed acamprosate ( Campral ) for 4 months . Subjects were volunteers treated at a hospital-based outpatient drug and alcohol treatment service , and were men and women who were 18 - 65 years old and with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , diagnosis of alcohol dependence . All subjects received usual medical care consisting of seven medical review s ( duration = 15 minutes ) over 4 months . Compliance therapy consisted of four to six individual sessions ( duration = 60 minutes ) in which beliefs about medication side effects , ambivalence , the benefits of treatment , treatment maintenance and relapse prevention were addressed and explored with motivational interviewing and cognitive behavior therapy techniques . RESULTS The outcome variables were number of days taking acamprosate , days to first drink , days to first relapse ( more than five drinks ) and days to first extended relapse ( greater than 2 consecutive days of more than five drinks ) . Intention-to-treat analyses showed little difference between the two groups in the outcome drinking measures . Nevertheless , the per- protocol analyses revealed that participation in three or more sessions of compliance therapy significantly increased adherence to acamprosate and improved overall treatment outcomes . CONCLUSIONS The present study highlights the need for psychological interventions to improve adherence to pharmacotherapy in the treatment of alcohol dependence and provides initial support for compliance therapy as an effective intervention The present research evaluated patients from 2 previous studies ( 1 conducted in Peoria , the other at Dartmouth ) during a 2- to 5-year posttreatment period . Results showed that 75 % of the Peoria sample and 76 % of the Dartmouth sample were able to discontinue alprazolam therapy , remain abstinent of any type of treatment for panic disorder , and maintain their acute-treatment clinical gains over this follow-up period . The degree to which patients ' anxiety sensitivity declined during treatment predicted relapse versus survival during the 1st 6 months of follow-up , when most relapses occurred . Implication s of these findings for benzodiazepine discontinuation , combined pharmacotherapy and psychotherapy , and relapse prevention in panic disorder are discussed
A Medline search of research on pharmacotherapy was undertaken , and a previous systematic review on the evidence -based pharmacotherapy of panic disorder was up date d. Selective serotonin reuptake inhibitors remain a first-line pharmacotherapy of panic disorder , with the serotonin noradrenaline reuptake inhibitor venlafaxine also an acceptable early option .
Temporary co-administration of benzodiazepines can be considered .
For patients not responding to first-line agents several pharmacotherapy options are available , but there is a notable paucity of data on the optimal choice
The evidence -based pharmacotherapy of panic disorder continues to evolve .
This paper review s data on first-line pharmacotherapy , evidence for maintenance treatment , and management options for treatment-refractory patients .