Use of fluoxetine, a selective serotonin-uptake inhibitor, in the treatment of obesity: a dose-response study (with a commentary by Michael Weintraub). Changes in weight during a 1-year trial of fluoxetine. Use of a serotonin re-uptake inhibitor, fluoxetine, in the treatment of obesity. Noradrenaline-selective versus serotonin-selective antidepressant therapy: differential effects on social functioning. Weight gain during long-term treatment of obsessive-compulsive disorder: a prospective comparison between serotonin reuptake inhibitors. A randomized, double-blind trial comparing sertraline and fluoxetine 6-month treatment in obese patients with Binge Eating Disorder Fluoxetine versus sertraline and paroxetine in major depressive disorder: changes in weight with long-term treatment. Lack of sexual dysfunction with the selective noradrenaline reuptake inhibitor reboxetine during treatment for major depressive disorder Fluoxetine increases resting energy expenditure and basal body temperature in humans. Comparative efficacy of selective serotonin reuptake inhibitors and tricyclics in the treatment of melancholia. Fluoxetine, a Selective Serotonin Uptake Inhibitor, for the Treatment of Outpatients with Major Depression A double-blind controlled clinical trial of fluoxetine and amitriptyline in the treatment of outpatients with major depressive disorder. Fluoxetine treatment of patients with major depressive disorder who failed initial treatment with sertraline. Effect of fluoxetine on noradrenergic mediated growth hormone release: A double blind, placebo-controlled study Controlled comparison of milnacipran and fluoxetine in major depression Serotoninergic manipulation, meal-induced satiety and eating pattern: effect of fluoxetine in obese female subjects. Differential effects of trimipramine and fluoxetine on sleep in geriatric depression. Effects of selective serotonin reuptake inhibitors on platelet serotonin parameters in major depressive disorder Fluoxetine versus amineptine in the treatment of outpatients with major depressive disorders. Switching to Reboxetine: An Efficacy and Safety Study in Patients With Major Depressive Disorder Unresponsive to Fluoxetine Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression. Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects. A Canadian multicenter, double-blind study of paroxetine and fluoxetine in major depressive disorder. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial Effect of serotonin re-uptake inhibition by fluoxetine on body weight and spontaneous food choice in obesity. FTO genotype, dietary protein, and change in appetite: the Preventing Overweight Using Novel Dietary Strategies trial. Reboxetine, a New Noradrenaline Selective Antidepressant, Is at Least as Effective as Fluoxetine in the Treatment of Depression Antidepressant treatment of chronic tension-type headache: a comparison between fluoxetine and desipramine. Pindolol and mianserin augment the antidepressant activity of fluoxetine in hospitalized major depressed patients, including those with treatment resistance. Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression. Selective serotonin reuptake inhibitor treatment of depression in symptomatic HIV infection and AIDS. Improvements in affective and somatic symptoms. Increasing the number of chews before swallowing reduces meal size in normal-weight, overweight, and obese adults. Efficacy and safety of long-term fluoxetine treatment of obesity--maximizing success. The effects of consuming frequent, higher protein meals on appetite and satiety during weight loss in overweight/obese men. Safe use of SSRIs in young adults: how strong is evidence for new suicide warning? Cytokines and serotonin transporter in patients with major depression Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians A comparative clinical trial of fluoxetine, mianserin and placebo in depressed outpatients
Pharmacologic measures which increase serotonergic activity in the brain decrease food consumption and lead to decreased weight in animals .  Fluoxetine , an inhibitor of serotonin reuptake , decreases food intake in animals and is associated with weight loss in depressed and otherwise healthy obese patients . To determine the most effective daily fixed dose which causes weight loss in nondepressed obese patients , fluoxetine ( 10 , 20 , 40 or 60 mg ) or placebo was administered once daily for 8 weeks to 655 patients consisting primarily of women ( mean age 40 years , mean weight 95 kg ) .  Diet and activity were not controlled . The placebo-treated patients lost 0.6 + /- 2.3 kg . With the 60-mg fluoxetine dose , patients lost an average of 4.0 + /- 3.9 kg ( P less than 0.001 ) , with intermediate responses at the lower doses . Weight loss was proportional to the initial body mass index ( weight/height squared ) . There were no statistically significant differences between any fluoxetine treatment group and placebo for discontinuations from the study . There were statistically significant dose-dependent increases in reports of asthenia , somnolence and sweating . Thus , fluoxetine 60 mg daily appears to be potentially effective for use in weight reduction OBJECTIVE Fluoxetine has been associated with weight loss during acute treatment , but no controlled studies of weight change during long-term treatment with fluoxetine or other selective serotonin reuptake inhibitors have been reported . Weights were assessed for patients whose depressive symptoms had disappeared with acute fluoxetine treatment . Patients were then r and omly assigned to continuation treatment with fluoxetine or placebo . METHOD Patients whose illness had remitted after 12 weeks of treatment with fluoxetine , 20 mg/day , were r and omly assigned to receive up to 38 weeks of treatment with fluoxetine or placebo .  Weight was assessed at each visit . Change in weight was analyzed during the initial 12 weeks of acute treatment and after 14 , 26 , and 38 weeks . Relationships between weight change and body mass index and between weight change and appetite change were assessed . RESULTS During the initial 4 weeks of therapy , a mean absolute weight decrease of 0.4 kg was observed for all patients . Among patients who completed 50 weeks of therapy , the mean absolute weight increase during continuation treatment was similar for both the placebo- and fluoxetine-treated groups . Weight increase was not related to initial body mass index but was related to both poor appetite at study entry and to improvement in appetite after recovery . No patients discontinued therapy because of weight gain . CONCLUSIONS Acute therapy with fluoxetine is associated with modest weight loss . After remission of depressive symptoms , weight gain for patients taking fluoxetine for longer periods is not different from that for patients taking placebo and is most likely related to recovery from depression Health risks associated with obesity are well known and compliance with st and ard regimens for weight reduction is frequently unsatisfactory . Fluoxetine is a specific inhibitor of serotonin re-uptake with very minimal affinity for serotonergic or other receptors . It causes a decrement in food intake in animals . Placebo or fluoxetine was given for up to 8 weeks to non-depressed , otherwise healthy , obese patients given minimal dietary advice . Patients given fluoxetine  lost 4.5 + /- 4.0 kg , significantly more than those receiving placebo , 1.4 + /- 0.1 kg . The weight loss was correlated with the degree of obesity in the  fluoxetine-treated patients .  Asthenia was the only event reported significantly more frequently by fluoxetine-treated patients ( 23 percent ) than by those treated with placebo ( 3 percent ) ( P less than 0.01 ) . Fluoxetine appears to be safe and effective in inducing weight loss over periods of up to 8 weeks The outcome of antidepressant therapy in terms of social functioning was evaluated in a r and omized , placebo-controlled , double-blind study comparing the selective noradrenaline reuptake inhibitor ( NARI ) , reboxetine , with the selective serotonin reuptake inhibitor ( SSRI ) fluoxetine . Of the 381 patients with major depression participating in the study , 302 patients were assessed using the new self-rating Social Adaptation Self-evaluation Scale ( SASS ) . Mean SASS total score at last assessment was superior ( p < 0.05 ) to placebo for both reboxetine and fluoxetine . Moreover , reboxetine was superior ( p < 0.05 ) to fluoxetine . Evaluation of the sensitivity to change in individual items by point-biserial correlation analysis showed a significant correlation between improvement in item score and reboxetine treatment in all but one item for the reboxetine-placebo comparison . In the fluoxetine-placebo comparison , a significant correlation was evident for only 12 of the 21 items . Direct comparison of reboxetine with fluoxetine revealed a significant correlation between change in item score and treatment for nine items , in favour of reboxetine . The association was maximal for six items , mainly related to negative self-perception and to active social behaviour . In the subset of patients in remission at last assessment ( n = 91 ) , the mean SASS total score for reboxetine was superior to that of both fluoxetine and placebo ( p < 0.05 ) . Point-biserial correlation analysis revealed that most items sensitive to change under active treatment in the total population did so with reboxetine ( 17 items ) or fluoxetine ( nine items ) in patients in remission . In the reboxetine-fluoxetine comparison , 14 items showed a significant association with reboxetine treatment . In conclusion , while social motivation and behaviour in depression are significantly affected by both noradrenergic and serotonergic antidepressant treatment , noradrenergic therapy seems particularly effective in improving negative self-perception and motivation towards action , result ing in a better quality of remission in terms of social functioning BACKGROUND The effect of extended anti-depressant treatment on weight has been poorly investigated . Also unknown is whether different compounds have differential effects . The aim of the present study was to assess changes in weight in obsessive-compulsive disorder ( OCD ) patients treated for 2.5 years with  clomipramine or selective serotonin reuptake inhibitors . METHOD 138 DSM-IV OCD patients who responded to 6-month acute treatment at the Mood and Anxiety Disorders Unit , Department of Neuroscience , University of Turin , Italy , were followed-up for 2 years while receiving open-label clomipramine , citalopram , fluoxetine , fluvoxamine , paroxetine , or sertraline .  Patients were consecutively recruited and followed from May 1998 to March 2003 . The mean percentage change in weight was compared for each group , as was the proportion of patients who had a > or = 7 % weight increase from baseline . RESULTS At the end of the 2.5-year study period , patients had gained a mean of 2.5 % of their body weight with respect to baseline ( 1.58 kg ) ; 14.5 % of the total sample experienced a significant ( > or = 7 % ) weight increase . Within each but the fluoxetine treatment group , paired t tests showed a significant increase in weight from baseline to final visit . Analysis of variance showed a significant difference between treatment groups ( p = .009 ) , with clomipramine being associated with the highest weight increase and fluoxetine and sertraline with the lowest . A higher proportion of clomipramine-treated patients ( 34.8 % ) gained > or = 7 % in weight as compared with sertraline and fluoxetine , which accounted for the lowest percentage of patients with a significant weight gain ( 4.5 % and 8.7 % , respectively ) , although this difference was not statistically significant . CONCLUSION Risk of weight gain during extended serotonin reuptake inhibitor treatment for OCD differs depending on which compound is used . The differences among antiobsessive drugs may affect compliance with medication and health risks Previous studies support the use of selective serotonin reuptake inhibitors ( SSRIs ) , in overweight patients with Binge Eating Disorder ( BED ) , but results are far from conclusive . Sertraline has been studied less extensively , and there have been a few studies concerning SSRIs that report follow-up data at more than 12 weeks of follow-up . The present study assesses the effectiveness of sertraline and fluoxetine over a period of 24 weeks in obese patients with BED ( DSM-IV-TR ) . Forty-two obese out patients were r and omized and assigned to one of two different drug treatments : 22 were treated with sertraline ( dose range : 100 - 200 mg/day ) and 20 with fluoxetine ( dose range : 40 - 80 mg/day ) . Subjects were assessed at baseline and at 8 , 12 , and 24 weeks of treatment for binge frequency , weight loss , and severity of psychopathology . No significant differences were found between the two treatments . After 8 weeks of treatment a significant improvement in the Binge Eating Scale score and a significant weight loss emerged . These results were maintained by responders ( weigh loss of at least 5 % of baseline weight ) over 24 weeks . The results suggest that a 6-month treatment with SSRI may be an effective option to treat patients with BED BACKGROUND The effects of extended selective serotonin reuptake inhibitor ( SSRI ) treatment on weight are not well characterized . Also unknown is whether different agents have differential effects . To examine these questions , we assessed weight changes in patients r and omly assigned to long-term treatment with  fluoxetine , sertraline , or paroxetine . METHOD Patients ( N = 284 ) with major depressive disorder ( DSM-IV ) were r and omly assigned to double-blind treatment with fluoxetine ( N = 92 ) , sertraline , ( N = 96 ) , or paroxetine ( N = 96 ) for a total of 26 to 32 weeks . The mean percent change in weight was compared for each group , as was the number of patients who had > or = 7 % weight increase from baseline . RESULTS Patients ( fluoxetine , N = 44 ; sertraline , N = 48 ; paroxetine , N = 47 ) who completed the trial were included in these analyses . Paroxetine-treated patients experienced a significant weight increase , fluoxetine-treated patients had a modest but nonsignificant weight decrease , and patients treated with sertraline had a modest but nonsignificant weight increase . The number of patients whose weight increased > 7 % from baseline was significantly greater for paroxetine-treated compared with either fluoxetine-treated or sertraline-treated patients . CONCLUSION Risk of weight gain during extended SSRI treatment differs depending on which SSRI is used & NA ; Sexual side‐effects due to antidepressant treatment are an important consideration when selecting a treatment regimen and can influence patient compliance . Sexual function during treatment with the selective noradrenaline reuptake inhibitor reboxetine , the selective serotonin reuptake inhibitor ( SSRI ) fluoxetine and placebo has been assessed in a multicentre , r and omized , 8‐week , double‐blind study of 450 patients diagnosed with major depressive disorder .  Sexual function was measured by the Rush Sexual Inventory completed by male and female patients and administered at baseline , week 4 and week 8 . The results indicate that reboxetine was similar to placebo and superior to fluoxetine in its effect on overall sexual function . There was a greater degree of sexual satisfaction in the reboxetine group compared to fluoxetine ( P = 0.02 ) . The percentage of female patients able to achieve orgasm increased during the study period for women who received reboxetine and placebo , but decreased for those who received fluoxetine . These results suggest that reboxetine may be of particular benefit for patients at risk for sexual dysfunction with SSRIs Humans lose weight when administered fluoxetine , an inhibitor of serotonin reuptake by nerve terminals . To determine whether increased energy expenditure contributes to this weight loss we admitted 20 nondepressed obese women to a metabolic unit where they were r and omly assigned to 3 wk of a 1.76-MJ/d formula diet and either 60 mg fluoxetine/d or a placebo .  Resting energy expenditure of the control subjects fell below normal after 5.6 + /- 0.6 d of energy restriction , whereas that of the fluoxetine-treated subjects increased by 4.4 + /- 1.8 % ( P < 0.005 ) within 3 d of commencing treatment . This increased resting energy expenditure then reversed and fell below normal after 9.8 + /- 0.9 d of energy restriction . Basal body temperature of the control subjects decreased insignificantly during the period of energy restriction , but that of the fluoxetine-treated subjects increased by 0.28 + /- 0.10 degrees C ( P < 0.05 ) within 3 d of commencing diet and drug treatment . Urinary norepinephrine excretion and the serum triiodothyronine concentration decreased equally in both groups . Despite identical energy intakes and equal nitrogen balance , the fluoxetine-treated subjects lost weight faster than the control subjects during the final week of energy restriction ( P < 0.05 ) . We propose that serotonin reuptake inhibition increases energy expenditure by increasing basal body temperature OBJECTIVE The popularity of selective serotonin reuptake inhibitors stems from their apparent efficacy for numerous disorders and their favorable side effect profile . However , several studies have suggested that selective serotonin reuptake inhibitors may be relatively ineffective for treating melancholia . The objective of this study was to compare the responses to fluoxetine and nortriptyline of older patients with both severe depression and heart disease . METHOD The outcome of 22 hospitalized patients with unipolar depression and heart disease who were treated with fluoxetine was compared to the outcome of 42 comparable patients treated with nortriptyline . The average age of the fluoxetine group was 73 years , and their mean pretreatment score on the Hamilton Depression Rating Scale was 26 ; the average age of the nortriptyline group was 70 , and their mean pretreatment Hamilton score was 28 . RESULTS Of the 42 nortriptyline-treated patients , 28 were responders , six were nonresponders , and eight dropped out . The intent-to-treat response rate was 67 % ( 28 of 42 ) , and the response rate of the melancholic patients who completed the nortriptyline trial was 83 % ( 20 of 24 ) . Of the 22 fluoxetine-treated patients , five were responders , 13 were nonresponders , and four dropped out . The intent-to-treat response rate was 23 % ( five of 22 ) , and the response rate of the melancholic patients who completed the fluoxetine trial was 10 % ( one of 10 ) . CONCLUSIONS Fluoxetine appears to be significantly less effective than nortriptyline for treating hospitalized elderly patients with unipolar major affective disorder , especially those with the melancholic subtype and concurrent cardiovascular disease In a double-blind , placebo-controlled study the authors found that fluoxetine , a potent and selective inhibitor of serotonin reuptake , was an effective antidepressant in moderately depressed , ambulatory out patients . Typical adverse effects reported by patients treated with fluoxetine  included agitation , nausea , fatigue , and insomnia . Compared to imipramine , fluoxetine was associated with fewer complaints of dry mouth , constipation , and dizziness Fluoxetine , a specific serotonin reuptake inhibitor , was compared to amitriptyline in the treatment of 51 out patients with primary major depressive disorder . After a 1-week placebo washout , patients were r and omly assigned to 5 weeks of treatment with fluoxetine or amitriptyline . Fluoxetine was found to have a therapeutic effect comparable to that of amitriptyline ; however , the fluoxetine treatment group had a better Efficacy Index-Side Effects rating and a lower incidence of anticholinergic autonomic side effects . Four amitriptyline-treated patients had to discontinue the study because of serious side effects , while in the fluoxetine treatment group there were no terminations due to side effects . The amitriptyline-treated patients gained significantly more weight than the fluoxetine-treated patients BACKGROUND This study was conducted to determine if patients with major depressive disorder who had previously failed treatment with one serotonin selective reuptake inhibitor ( SSRI ) would respond to a different SSRI . METHOD Adult out patients ( N = 106 ) with DSM-III-R major depressive disorder and a history of either intolerance ( N = 34 ) or nonresponse ( N = 72 ) to treatment with sertraline  were treated with fluoxetine ( mean dose = 37.2 mg/day ) in a st and ardized , open-label , 6-week clinical trial . Outcome was assessed at each visit using the Hamilton Rating Scale for Depression ( HAM-D ) , the Clinical Global Impressions ( CGI-Improvement and CGI-Severity ) scales , and the Patient 's Global Improvement ( PGI ) scale . RESULTS Ninety-one patients ( 86 % ) completed the study . Sixty-seven patients ( 63 % ) responded to fluoxetine ( i.e. , experienced > or = 50 % reduction in HAM-D28 total score at endpoint versus baseline ) . In addition , clinical ly and statistically significant improvements were noted on all measures of depressive symptoms and global functioning . There was a nonsignificant trend for patients with a history of less vigorous sertraline trials to respond more favorably to fluoxetine . Fluoxetine therapy was generally well tolerated , and there were only slight differences in adverse events reported by patients who had been intolerant to sertraline versus those who were nonresponders . CONCLUSION These findings indicate that fluoxetine and sertraline , two widely used SSRIs , are not interchangeable . Patients who either have had trouble tolerating or have not responded to sertraline may do well on fluoxetine treatment Twelve patients with DSM-III-R major depressive illness were tested for growth hormone ( GH ) response to desipramine ( DMI ) , a noradrenergic ( NA ) reuptake inhibitor . The response is mediated by NA alpha 2 receptors . They were then r and omly assigned to treatment under double-blind conditions with either fluoxetine , the highly selective serotonin reuptake inhibitor or placebo . After 4 weeks they were retested . Fluoxetine but not placebo was effective in promoting recovery in four of the six patients treated . Patients treated with fluoxetine showed a significant decrease in DMI-mediated GH release irrespective of therapeutic outcome . This is consistent with marked alteration of NA function and raises questions as to the selectivity of fluoxetine The efficacy and the tolerance of milnacipran ( 100 mg/day ) , a second generation antidepressant which equipotently inhibits both noradrenaline and serotonin reuptake , was compared to fluoxetine ( 20 mg/day ) , a selective serotonin reuptake inhibitor , in two parallel groups of , respectively , 97 and 93 major depressive out patients . The duration of the study was 6 weeks , with assessment s every 2 weeks by means of the Montgomery and Asberg depression scale ( MADRS ) , the Hamilton depression scale , the clinical global impressions ( CGI ) , and a checklist of symptoms and side-effects . Results showed significant superiority of fluoxetine over milnacipran on most rating instruments : MADRS ( P=0.01 ) including five individual items , Hamilton depression scale ( P=0.002 ) including ten individual items , CGI of severity ( P=0.01 ) and therapeutical index ( P=0.002 ) . On visual analogue scales assessing the clinical profile of the compounds , fluoxetine was rated as exhibiting more psychostimulating activity than milnacipran ( P=0.0008 ) . The tolerance of the two antidepressants was very similar , with the exception of symptoms of dizziness which were more frequently reported with milnacipran ( P=0.01 ) . These differences in efficacy favoring fluoxetine could result from the selection of a dose of milnacipran below the optimal therapeutic dose for this type of psychiatric patients or to the administration of the compounds in single daily intakes , whereas milnacipran possesses a plasma elimination half-life of only 7 Twelve nondepressed healthy female obese subjects ( BMI > 30 kg/m2 ) took part in a study which conformed to a double-blind r and omized crossover design . Each subject acted as her own control across 2 weeks of treatment with either 60 mg of the 5-HT reuptake inhibitor fluoxetine or matching placebo . On days 7 and 14 of both treatment phases subjects were provided with fixed energy lunch meals high in either CHO or fat . The effect of these meals on satiety during the fluoxetine and placebo phases was assessed by a battery of procedures . Subjects felt less hungry after consuming the high CHO meal than after consuming the high-fat meal . They also felt less hungry when taking fluoxetine than when taking the placebo . Analysis of energy intake from the test meal revealed a main effect of prior lunch meal type ( high CHO or high fat ) and a main effect of drug treatment . Subjects consumed an average of 574 kcal following the high CHO meal compared to 689 kcal following the high-fat meal . Subjects also consumed an average of 532 kcal when taking fluoxetine compared to 730 kcal when taking the placebo . Fluoxetine did not exert any significant effects on macronutrient selection . Mean daily energy intake , calculated from food diary records , was 1881 kcal when subjects were taking the placebo compared to 1460 kcal when taking fluoxetine ( a reduction of 22.4 % ) . Fluoxetine treatment produced a significant weight loss of 1.97 kg over the two weeks of treatment compared to a weight loss of only 0.04 kg on placebo The effects of trimipramine , a tricyclic antidepressant ( TCA ) with atypical pharmacological properties , and fluoxetine , a selective serotonine reuptake inhibitor ( SSRI ) , were compared in an exploratory analysis using mood and polysomnographic parameters during a six-week double-blind trial in 19 depressed geriatric patients . In sleep EEG measures , trimipramine demonstrated clear-cut effects on sleep measures result ing in higher values for sleep efficiency , total sleep time , stage 2 sleep , and shorter wake time . Under fluoxetine treatment , the proportion of REM sleep was decreased and REM latency was lengthened , whereas no change in REM sleep parameters was observed in the trimipramine group . The present data suggest that early antidepressant effects of medication occur independently of drug-induced changes in objective measures of sleep , i.e. suppression of REM sleep The effects of treatment with serotonin ( 5-HT ) reuptake inhibitors on platelet 5-HT2 receptors , 5-HT reuptake sites an 5-HT uptake were studied in a double-blind trial comparing two selective serotonin reuptake inhibitors ( SSRI ) , paroxetine , and fluoxetine , for the treatment of major depression . Hamilton Depression Rating Scale ( HAM-D ) scores and platelet 5-HT parameters were determined in 21 depressed patients at baseline , after 4 and 8 weeks of treatment , and were compared to 21 healthy controls . Antidepressant treatment did not significantly alter the density of 5-HT reuptake sites , labelled with [3H]paroxetine , or 5-HT2 receptors , labelled with [3H]LSD . However , a strong correlation was observed between the HAM-D suicidality item and 5-HT2 receptor density at baseline . A marked increase in platelet 5-HT2 receptors at baseline was observed in suicidal depressed patients compared to those with no suicidal ideation and healthy controls . Changes in [3H]paroxetine Bmax and in [3H]5-HT uptake significantly correlated with change in HAM-D score at 4 and 8 weeks respectively . These results confirm previous reports of an association between suicidality and platelet 5-HT2 receptor upregulation . Our data also lends support to the use of platelet 5-HT parameters as indicators of antidepressant efficacy , particularly in suicidal depressed patients Fluoxetine , a selective serotonin reuptake inhibitor , was compared to amineptine , a tricyclic antidepressant agent , in the treatment of 63 out patients with major depressive disorders of mild or moderate severity . Patients were r and omly assigned to 6 weeks of treatment with either fluoxetine or amineptine . Fluoxetine was found to have a more marked therapeutic effect than that of amineptine : better efficacy , fewer side-effects , and quicker and better improvement on the self evaluation scales The aim of the present study was to evaluate the efficacy and safety of an immediate switch to reboxetine , a selective noradrenaline reuptake inhibitor ( selective NRI ) , in patients with depression unresponsive to the selective serotonin reuptake inhibitor ( SSRI ) fluoxetine . The study included 128 adult out patients with DSM-IV major depressive disorder ( MDD ) who had not responded to at least 6 to 12 weeks of fluoxetine treatment , with at least 3 weeks of treatment on a minimum dose of 40 mg/d . Patients were switched , without a washout period , to reboxetine 4 mg twice daily , with the possibility of increasing the dose to 10 mg/d ( given in divided doses ) after 4 weeks of treatment . Efficacy was assessed using the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) and the Clinical Global Impression Improvement ( CGI-I ) and Severity ( CGI-S ) scales . Safety was evaluated by recording spontaneously reported adverse events . A statistically significant ( P < 0.001 ) improvement in the mean total HAM-D-17 score was seen from baseline by week 1 of treatment with reboxetine , and the improvement continue to week 8 . CGI-I and CGI-S scores were similarly improved . The switch to reboxetine was well tolerated ; the most common treatment-emergent adverse events were insomnia , headache , dry mouth , diaphoresis , and constipation , all of which were mild to moderate in severity and decreased in frequency as the study progressed . Immediate switching to reboxetine appears to be a safe and effective treatment for patients with depression who have failed to respond to an adequate dose of fluoxetine BACKGROUND Major depression with high levels of anxiety ( anxious depression ) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment . It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors . For this reason , using head-to-head acute treatment comparison , we compared efficacy and tolerability of fluoxetine , sertraline , and paroxetine among depressed patients with high levels of anxiety . METHODS Patients ( N = 108 ) with DSM-IV major depression and high levels of anxiety ( a HAM-D-Anxiety/Somatization Factor score > or = 7 ) were r and omized to fluoxetine , sertraline , or paroxetine treatment in a double-blind fashion . Changes in overall depression and anxiety were assessed . RESULTS Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores . Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores , except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score . There were no significant differences across treatments in percentages of patients with substantial emergence , any worsening , or improvement at endpoint in individual HAM-D Items 9 ( agitation ) , 10 ( psychic anxiety ) , and 11 ( somatic anxiety ) . Overall , all treatments were well tolerated . CONCLUSION These data showed no significant differences in efficacy and tolerability of fluoxetine , sertraline , and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression . Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression OBJECTIVE Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both , we investigated whether tryptophan , an amino acid with both antidepressant-augmenting and hypnotic effects , would benefit patients with depression at the beginning of treatment with fluoxetine .  DESIGN R and omized , double-blind , placebo-controlled trial . PATIENTS Thirty individuals with major depressive disorder . INTERVENTIONS Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan ( 2 to 4 g per day ) or placebo . OUTCOME MEASURES Mood was assessed using the 29-item Hamilton Depression Rating Scale ( HDRS-29 ) and the Beck Depression Inventory ( BDI ) . Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using st and ard procedures . RESULTS During the first week of treatment , there was a significantly greater decrease in HDRS-29 depression scores , and a similar trend in BDI scores , in the tryptophan/fluoxetine group than in the placebo/fluoxetine group . No significant differences were noted at later time points . With respect to sleep measures , there was a significant group-by-time interaction for slow-wave sleep at week 4 . Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group , but not in the tryptophan/fluoxetine group . No cases of serotonin syndrome occurred , and the combination was well tolerated , although the 4 g per day dosage of tryptophan produced daytime drowsiness . CONCLUSIONS Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep . Further large-scale studies are needed to confirm these initial findings BACKGROUND Recent studies have suggested clinical differences among selective serotonin reuptake inhibitors . In a 12-week r and omized , multicenter , double-blind trial , the antidepressant and anxiolytic efficacy of the selective serotonin reuptake inhibitors paroxetine and fluoxetine was compared in patients with moderate to severe depression . METHODS A total of 203 patients were r and omized to fixed doses ( 20 mg/day ) of paroxetine or fluoxetine for the first six weeks of therapy . From week 7 - 12 , dosing could be adjusted biweekly , as required ( paroxetine 20 - 50 mg/day , and fluoxetine 20 - 80 mg/day ) . The mean prescribed doses were paroxetine 25.5 mg/day ( range 20.0 - 40.2 mg/day ) , and fluoxetine 27.5 mg/day ( range 20.0 - 59.5 mg/day ) . Emergence of motor nervousness or restlessness was assessed using the ESRS scale for akathisia . RESULTS Both active treatments demonstrated comparable antidepressant efficacy ( HAM-D , CGI ) . Anxiolytic activity of the two drugs ( COVI , STAI , HAM-D ) was also comparable . However , paroxetine was found to be superior to fluoxetine on two subscore measures at week 1 of therapy ( HAM-D Agitation item , p < 0.05 ; Psychic Anxiety item , p < 0.05 ) , with no differences detected after week 2 . The overall incidence of adverse effects was comparable in the two treatment groups . Constipation , dyspepsia , tremor , sweating and abnormal ejaculation were more common in paroxetine-treated subjects , whereas nausea and nervousness were more frequent in fluoxetine-treated patients . Weight loss was more common in the fluoxetine versus paroxetine group ( 11.88 % versus 2.94 % , respectively ) . ESRS scores for akathisia were low throughout the study and showed little change . LIMITATIONS Differences observed between the two drugs in antianxiety effects were limited to two measures of anxiety among several others . DISCUSSION The data indicate that paroxetine and fluoxetine have comparable antidepressant and anxiolytic efficacy .  Paroxetine appears to produce an earlier improvement in agitation and psychic anxiety symptoms compared with fluoxetine BACKGROUND Recent reports describe discontinuation-emergent adverse events upon cessation of selective serotonin reuptake inhibitors including dizziness , insomnia , nervousness , nausea , and agitation . We hypothesized that interruption of fluoxetine treatment would be associated with fewer discontinuation-emergent adverse events than interruption of sertraline or paroxetine treatment , based on fluoxetine 's longer half-life . METHODS In this 4-week study , 242 patients with remitted depression receiving maintenance therapy with open-label fluoxetine , sertraline , or paroxetine for 4 - 24 months had their maintenance therapy interrupted with double-blind placebo substitution for 5 - 8 days . The  Symptom Question naire ( SQ ) , the Discontinuation-Emergent Signs and Symptoms checklist , the 28-item Hamilton Depression Rating Scale , and the Montgomery-Asberg Depression Rating Scale  were used to assess somatic distress and stability of antidepressant response . RESULTS Two hundred twenty patients ( 91 % ) completed the study . Following interruption of therapy , fluoxetine-treated patients experienced fewer discontinuation-emergent events than either sertraline-treated or paroxetine-treated patients ( p < .001 ) . The mean SQ somatic symptom scale score in fluoxetine-treated patients was significantly lower than that in sertraline-treated and paroxetine-treated patients ( p < .001 ) . Fluoxetine-treated patients also experienced less reemergence of depressive symptoms than sertraline-treated or paroxetine-treated patients ( p < .001 ) . CONCLUSIONS Abrupt interruption of antidepressant therapy for 5 - 8 days was associated with the emergence of new somatic and psychological symptoms in patients treated with paroxetine and to a lesser degree sertraline , with few symptoms seen with fluoxetine The effect of fluoxetine on body weight and spontaneous food choice was studied in twenty-three healthy , non-depressed , obese females on an outpatient basis . After a one week placebo run-in period , subjects were r and omized to receive either fluoxetine ( FXT ) 60 mg daily ( n = 11 ) or placebo ( P ) ( n = 12 ) for 6 weeks in a double blind study design .  BMI ( 35.2 + /- 0.8 vs 36.4 + /- 1.3 kg/m2 , mean + /- s.e.m . ) and age ( 38.1 + /- 239 vs 37.3 + /- 2.7 years ) were not different in either group . No specific diet was prescribed . On four separate days per 14 days food records were collected . Data were analysed with the use of food composition tables . Statistical analysis was performed using Student 's t test for independent sample s for data on body weight and calorie intake . Macro-nutrient composition of the diet was analysed using multivariate analysis of variance and post hoc Student 's t test for independent sample s. All subjects lost weight during fluoxetine treatment . Mean ( + /- s.e.m . ) weight loss in the fluoxetine treated group was 3.6 + /- 0.5 kg , compared to a mean weight gain of 0.3 + /- 0.5 kg in the placebo treated group ( P less than 0.001 ) . In all patients food intake was reduced during fluoxetine treatment and this reduction could fully account for the observed weight loss . The mean total caloric intake per day was significantly lower during fluoxetine treatment compared with placebo ( FXT 1123 + /- 118 kcal vs P 1845 + /- 87 kcal , P less than 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND A common obesity-risk variant rs9939609 in the fat mass- and obesity-associated ( FTO ) gene was recently shown to affect appetite , and the gene is sensitive to the regulation of amino acids . OBJECTIVE We examined the interaction between FTO genotype and protein intake on the long-term changes in appetite in a r and omized controlled trial . DESIGN We genotyped FTO rs9939609 in 737 overweight adults in the 2-y Preventing Overweight Using Novel Dietary Strategies  trial and assessed 4 appetite-related traits including cravings , fullness , hunger , and prospect i ve consumption . RESULTS We showed that dietary protein significantly modified genetic effects on changes in food cravings and appetite scores at 6 mo after adjustment for age , sex , ethnicity , baseline body mass index , weight change , and baseline value for respective outcomes ( P-interaction = 0.027 and 0.048 , respectively ) . The A allele was associated with a greater decrease in food cravings and appetite scores in participants with high-protein-diet intake ( P = 0.027 and 0.047 , respectively ) but not in subjects in the low-protein-diet group ( P = 0.384 and 0.078 , respectively ) . The weight regain from 6 to 24 mo attenuated gene-protein interactions . Protein intakes did not modify FTO genotype effects on other appetite measures . CONCLUSION Our data suggest that individuals with the FTO rs9939609 A allele might obtain more benefits in a reduction of food cravings and appetite by choosing a hypocaloric and higher-protein weight-loss diet . This trial was registered at clinical trials.gov as NCT00072995 The clinical profile of reboxetine , a selective noradrenaline reuptake inhibitor , was compared with that of the selective serotonin reuptake inhibitor fluoxetine and placebo in a double-blind , multicenter , parallel-group clinical trial of patients with major depression . Among the 381 patients treated with reboxetine 8 to 10 mg/day , fluoxetine 20 to 40 mg/day , or placebo for up to 8 weeks , a statistically significant greater reduction in the mean Hamilton Rating Scale for Depression ( 21-item HAM-D ) total score ( the primary efficacy variable ) was seen for both active treatment groups compared with placebo ( p < 0.024 ) . A significantly greater proportion of patients treated with either reboxetine or fluoxetine also achieved a response ( ≥50 % reduction in HAM-D ) or remission ( HAM-D ≤10 points ) than those who received placebo ( p < 0.01 for both analyses ) . Similar findings were recorded in a sub population of severely ill patients , with statistically significantly greater decreases in the mean HAM-D total score between both active treatment groups compared with placebo ( p < 0.024 ) . Additional efficacy assessment s ( Montgomery-Åsberg Depression Rating Scale , Clinical Global Impression ) reflected the primary efficacy analysis , with both active treatments offering comparable efficacy that was superior to that of placebo . Reboxetine and fluoxetine are more effective  than placebo in the treatment of major depression . Futhermore , both antidepressants are well tolerated but possess different adverse event profiles Amitriptyline , which is a noradrenaline reuptake and 5-HT reuptake inhibitor , has an established role in the management of  chronic tension-type headaches .  In a single-blind study , patients with chronic tension-type headache were r and omized to either fluoxetine 20 mg ( a selective 5-HT reuptake inhibitor ) or desipramine 75 mg ( a selective noradrenaline reuptake inhibitor ) and followed for 12 weeks to compare the effectiveness of the two drugs in improving headache , and to assess whether pain control is related to changes in depression . Patients were evaluated at weekly intervals on an analog pain-rating scale and at 4-weekly intervals on the Montgomery and Asberg Depression Rating Scale ( MADRS ) , the MOS general health status question naire ( SF36 ) , the Hospital Anxiety and Depression Scale ( HADS ) , and a side effects checklist .  Eighteen patients were r and omized to take fluoxetine and 19 to take desipramine . Of the 25 patients who completed the trial , 12 were on  fluoxetine and 13 were on desipramine . There was no significant difference between the two groups at baseline nor in change of pain ; reduction in use of analgesic medication ; nor change in the HADS , MADRS , or SF36 scores at 12 weeks , but 72 % of patients who completed the study improved , and this improvement almost exactly mirrored the improvement on the MADRS . The results from this trial are compatible with the notion that the beneficial effect of antidepressants in  chronic tension-type headache  is indirect , mediated by an effect on depression , and not more , dependent on serotonin reuptake inhibition than noradrenaline reuptake inhibition The aims of this study were to examine whether pindolol , a serotonin ( 5-hydroxytryptamine [5-HT])-1A receptor antagonist , and mianserin , a 5-HT2A/C and alpha2-adrenoceptor ( alpha2-AR ) antagonist , may augment the clinical efficacy of fluoxetine , a selective serotonin reuptake inhibitor , and shorten the latency of onset of antidepressive activity in the treatment of major and treatment-resistant depression ( TRD ) . Ten days after admission to the hospital , 31 major depressed patients were r and omly assigned using a double-blind , controlled design to receive fluoxetine 20 mg daily , fluoxetine 20 mg daily plus pindolol 7.5 mg daily , or fluoxetine 20 mg plus mianserin 30 mg daily for 5 weeks . The 17-item Hamilton Rating Scale for Depression ( HAM-D ) score was the primary outcome measure . Analysis of efficacy was conducted according to the intent-to-treat analysis principle considering the change from baseline to endpoint . It was found that fluoxetine plus pindolol and fluoxetine plus mianserin were significantly more effective than fluoxetine alone . Using an outcome measure of 50 % reduction in the HAM-D , a 60 % response rate was found in patients treated with either fluoxetine plus pindolol or fluoxetine plus mianserin compared with a 9 % response rate in patients treated with fluoxetine alone . The HAM-D score 1 week after starting fluoxetine plus mianserin decreased more than 4 points and was significantly greater than that obtained by fluoxetine alone . The results suggest that pindolol and mianserin augment the efficacy of fluoxetine in the treatment of TRD and that mianserin , but not pindolol , may significantly shorten the latency of onset of antidepressive action when combined with fluoxetine Abstract There is evidence of derangement of oxidant and antioxidant defense systems in depression . The present study examined the effects of fluoxetine and citalopram , st and ard selective serotonin re-uptake inhibitors , on lipid peroxidation , superoxide dismutase ( SOD ) activity and ascorbic acid concentrations . For this , a prospect i ve open-labeled , r and omized design was utilized . Patients with major depression ( n = 62 ) were compared with age- and sex-matched healthy volunteers ( n = 40 ) . There was a significant increase in serum SOD , serum MDA and decrease in plasma ascorbic acid levels in patients of major depression as compared to control subjects . The trend reversed significantly after treatment with fluoxetine and citalopram . Results indicate a greater reduction in oxidative stress with citalopram than fluoxetine . The Hamilton Rating Scale for Depression ( HRSD ) score also improved with fluoxetine and citalopram treatment . These findings indicate that major depression is associated with increased levels of serum SOD , serum MDA and decreased levels of plasma ascorbic acid . Treatment with fluoxetine and citalopram reversed these biochemical parameters . This study can be used as a predictor of drug response by fluoxetine and citalopram in major depression OBJECTIVE The atypical subtype of depression appears to be both well vali date d and common . Although monoamine oxidase inhibitors are effective in treating atypical depression , their side effects and prescription-associated dietary restrictions reduce their suitability as a first-line treatment . The objective of this study was to estimate the efficacy of the selective serotonin reuptake inhibitor ( SSRI ) fluoxetine in the treatment of major depression with atypical features . METHOD One hundred fifty-four subjects with DSM-IV major depression who met the Columbia criteria for atypical depression were r and omly assigned to receive fluoxetine , imipramine , or placebo for a 10-week clinical trial . Imipramine was included because its known efficacy for treatment of atypical depression helped to calibrate the appropriateness of the study group . RESULTS In both intention-to-treat and completer groups , the effectiveness of both fluoxetine and imipramine was significantly better than that of placebo . The two medications did not differ from each other in effectiveness . Significantly more patients dropped out of treatment with imipramine than with fluoxetine . Before treatment , patients on average rated themselves as very impaired on psychological dimensions of general health and moderately impaired on physical dimensions , compared with population norms . The self-ratings of patients who responded to treatment essentially normalized on these measures . CONCLUSIONS Despite earlier data that SSRIs might be the treatment of choice , fluoxetine appeared to be no better than imipramine in the treatment of atypical depression , although fluoxetine was better tolerated than imipramine Somatic symptoms often complicate the diagnosis and psychopharmacological treatment of depression in HIV illness . We treated 33 depressed HIV-positive men and women with medically symptomatic HIV or AIDS ( CDC stages 2B , 2C , 3B , or 3C ) in a 6 week open-label trial with sertraline , paroxetine , or fluoxetine , to assess their effectiveness and tolerability . We further assessed whether treatment of depression result ed in a reduction in both affective and somatic symptoms in this medically ill population . Twenty-four subjects ( 73 % ) completed the trial ( 7 on sertraline , 7 on paroxetine , 10 on fluoxetine ) , 20 ( 83 % ) of whom were clinical responders . Nine dropped out within 1 - 3 weeks of treatment because of adverse effects , mostly agitation , anxiety , and insomnia . Subjects who completed 6 weeks of SSRI treatment experienced significant reductions in both affective and somatic symptoms , many of the latter having been attributed to HIV rather than depression . These results suggest that , even in later stages of HIV illness , the contribution of depression to perceived somatic symptoms may be significant , and that these symptoms may improve with antidepressant treatment Eating slowly contributes to a lower risk of obesity , probably because it could aid appetite control .  Chewing thoroughly is an effective strategy to reduce eating rate ; however , insufficient data are available to demonstrate the relationship between such an eating behavior and energy intake . To investigate the effect of increasing the number of chews before swallowing on meal size , a r and omized cross-over trial was conducted in 18- to 45-year-old normal-weight , overweight , and obese participants ( n=45 ) who were recruited from the local community ( Ames , IA ) . After assessment of baseline number of chews , participants were asked to attend three test sessions to eat pizza for lunch until comfortably full by chewing each portion of food either 100 % , 150 % , or 200 % of their baseline number of chews before swallowing . Two-way analysis of variance was used to test the effect of treatment and body-weight status , as well as their interactions on food intake , meal duration , eating rate , and appetite at meal termination . Appetite data during 60 minutes were analyzed by repeated measures analysis of variance . Food intake in the sessions with 150 % and 200 % of their baseline number of chews was reduced significantly , by 9.5 % and 14.8 % , respectively , compared with the 100 % session . Increasing the number of chews also prolonged meal duration and reduced eating rate . However , subjective appetite at meal termination or during the immediate postpr and ial period did not differ . These data indicate that increasing the number of chews before swallowing might be a behavioral strategy to reduce food intake and potentially aid body-weight management Obesity is a major health care concern because of its associated medical complications and increased mortality . Despite a myriad of short-term weight loss strategies and the motivation of improving health , patients have difficulty maintaining reduced weight . Pharmacologic agents , such as fluoxetine , a selective serotonin uptake inhibitor , have been investigated as adjunctive therapy to st and ard weight management programs . Extended therapy with fluoxetine has demonstrated clinical ly meaningful benefits on weight loss and obesity-associated medical conditions in double-blind placebo-controlled studies . However , the magnitude of these benefits for individuals vary . Such findings are consistent with the belief that the obesity syndrome has differing etiologies . Accordingly not all patients are likely to benefit from a particular therapy . Studies should identify patient subgroups that are more likely to respond to a specific therapy . In this study of 719 fluoxetine-treated and 722 placebo treated patients in four multicenter , r and omized , double-blind , long-term clinical trials , we investigated possible predictors of a beneficial long-term outcome from fluoxetine therapy . Patients ' age , current smoking activity , and baseline uric acid concentration were predictors of a meaningful long-term treatment effect . Further review of the weight loss patterns of patients achieving long-term success provided the basis for a treatment monitor . Use of the predictors and the treatment monitor are strategies to maximize the benefits of therapy through improved patient selection and monitoring during a therapeutic program The purpose of this study was to determine the effects of dietary protein and eating frequency on perceived appetite and satiety during weight loss . A total of 27 overweight/obese men ( age 47 ± 3 years ; BMI 31.5 ± 0.7 kg/m(2 ) ) were r and omized to groups that consumed an energy-restriction diet  ( i.e. , 750 kcal/day below daily energy need ) as either higher protein ( HP , 25 % of energy as protein , n = 14 ) or normal protein ( NP , 14 % of energy as protein , n = 13 ) for 12 weeks . Beginning on week 7 , the participants consumed their respective diets as either 3 eating occasions/day ( 3-EO ; every 5 h ) or 6 eating occasions/day ( 6-EO ; every 2 h ) , in r and omized order , for 3 consecutive days . Indexes of appetite and satiety were assessed every waking hour on the third day of each pattern . Daily hunger , desire to eat , and preoccupation with thoughts of food were not different between groups . The HP group experienced greater fullness throughout the day vs. NP ( 511 ± 56 vs. 243 ± 54 mm · 15 h ; P < 0.005 ) . When compared to NP , the HP group experienced lower late-night desire to eat ( 13 ± 4 vs. 27 ± 4 mm , P < 0.01 ) and preoccupation with thoughts of food ( 8 ± 4 vs. 21 ± 4 mm ; P < 0.01 ) . Within groups , the 3 vs. 6-EO patterns did not influence daily hunger , fullness , desire to eat , or preoccupation with thoughts of food . The 3-EO pattern led to greater evening and late-night fullness vs. 6-EO but only within the HP group ( P < 0.005 ) . Collectively , these data support the consumption of HP intake , but not greater eating frequency , for improved appetite control and satiety in overweight/obese men during energy restriction-induced weight loss Mr. B , age 20 , has taken a semester leave from college because of gradually worsening depressed mood . Over the past 2 months he has lost interest in jogging and playing piano -- which he usually enjoys . He reports reduced libido , middle insomnia , loss of appetite , feeling as if his head is " full of cotton , " trouble concentrating , and waking in the morning with a sense of dread . His anxiety dissipates during the day , but he continues to feel sad and sometimes weepy , which is unusual for him . [ ILLUSTRATION OMITTED ] Mr. B reports feeling hopeless at times and has had vague thoughts about life being " not worth it if I continue to feel like this " but denies specific suicide plans . Your initial impression is that Mr. B is in the midst of a major depressive episode and that a selective serotonin reuptake inhibitor ( SSRI ) is indicated . As you finish taking his history , you run through your mind the pros and cons of the recommendation you will make to him . Do SSRIs raise or lower the risk for suicidal behavior in young adults such as Mr. B ? The answer is complicated and goes beyond an " either/or " question , as the FDA acknowledged in May 2007 when it : * extended the black-box warning of increased suicidality risk with antidepressants to cover adults age 18 to 24 as well as children and adolescents * included language in the warning about the benefits of treating depression and the suicide risk associated with untreated depression , given concerns about declining antidepressant prescriptions and rising suicides among youth . ( 1 ) To help you make informed decisions when treating depression in adults , this article review s the studies leading up to and following the FDA 's meta- analysis of antidepressant trial data in patients age 18 and older . Our goal is to provide a framework for clinical treatment of adults age 18 to 24 and those age [ greater than or equal to]25 . First hints of suicidality  SSRIs revolutionized depression treatment . From 1985 to 1999 , annual U.S. antidepressant prescriptions quadrupled , with SSRIs accounting for 70 % of the increase ( see " Antidepressants and suicide risk , 1985 to 2007 , " pages 36 - 37 ) . At the same time , the age-adjusted suicide rate : * dropped 22.5 % for women ( who account for twice as many antidepressant prescriptions as men ) * dropped 12.8 % for men ( without change in the rank order of suicide methods ) . ( 2 ) For many patients , increased antidepressant use improved treatment of major depressive and other antidepressant-responsive disorders . In 1990 , however , case reports suggested SSRIs might cause suicidal thoughts or behavior . ( 3 ) Hypothesized mechanisms included increased aggression ( 4 ) and akathisia . ( 5 ) An FDA review found no proof , and a meta- analysis of data from 17 double-blind , r and omized , controlled trials found no association between fluoxetine and suicidal thoughts or behavior . ( 6 ) The debate rekindled in June 2003 when the British Committee on Safety of Medicines warned against using paroxetine or venlafaxine in children . After conducting its own meta- analysis , the FDA in 2004 ordered a black-box warning about suicidality and the use of  antidepressants in children and adolescents ( Box ) . ( 7 ) After the pediatric ' black box . '  Antidepressant prescriptions for  children and adolescents declined in the years 2003 to 2004 , as did diagnosis of pediatric depression . ( 8 - 10 ) Antidepressant prescribing also showed signs of shifting from general practitioners to psychiatrists . ( 8) At the same time , the suicide rate  among youth age 60 ,  SSRI prescriptions continued to rise and suicide rates fell , ( 9 ) a pattern of change consistent with antidepressants protecting against suicide . An independent meta- analysis by Bridge et al ( 12 ) examined the pediatric trial data used in the FDA meta- analysis plus 7 additional studies . Altered cytokine secretion as a mechanism in the etiology of depression is still obscure . The serotonin transporter ( 5-HTT ) may play an important role in the termination of serotonergic neurotransmission by serotonin ( 5-HT ) uptaking into presynaptic neurons and representing as an initial action site for selective 5-HTT reuptake inhibitors ( SSRI ) . In our study , we evaluated whether cytokines and 5-HTT acted as biological markers for depression . Blood sample s were collected from 42 participants . The differences in cytokine and 5-HTT mRNA expressions of leukocytes were assessed between the patients with major depression ( n=20 ) and the healthy controls ( n=22 ) , along with the measurements prior and after treatment with a SSRI , fluoxetine , for 3 months in the follow-up patient group ( n=8 ) . The results revealed that the mRNA expressions of IL-1beta , IL-6 , IFNgamma , TNFalpha , and 5-HTT were higher in the depressed patients than those of the healthy controls . The higher level of mRNA expressions of IFNgamma and 5-HTT diminished after fluoxetine treatment . Furthermore , we found a positive correlation between 5-HTT and cytokines mRNA expressions in total participants , which suggested that pro-inflammatory cytokines and 5-HTT might play critical roles in the pathogenesis of major depression and that their levels were affected by chronic treatment with 5-HTT inhibitors CONTEXT Selective serotonin reuptake inhibitors ( SSRIs ) are the most commonly prescribed class of antidepressant , yet it is not known whether one SSRI is more effective than another . OBJECTIVE To compare the effectiveness of 3 SSRIs ( paroxetine , fluoxetine , and sertraline ) in depressed primary care patients . DESIGN Open-label , r and omized , intention-to-treat trial , with patient enrollment occurring in April-November 1999 . SETTING Thirty-seven clinics in 2 US primary care research networks . PATIENTS A total of 573 depressed adult patients for whom their primary care physician thought that antidepressant therapy was warranted and who completed a baseline interview . INTERVENTIONS Patients were r and omly assigned to receive paroxetine ( n = 189 ) , fluoxetine ( n = 193 ) , or sertraline ( n = 191 ) for 9 months . Primary care physicians were allowed to switch patients to a different SSRI or non-SSRI antidepressant if they did not adequately respond to or tolerate the initial SSRI . MAIN OUTCOME MEASURES The primary outcome measure was change in the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) Mental Component Summary score ( range , 0 - 100 ) , compared across treatment groups at 1 , 3 , 6 , and 9 months . Secondary outcomes included other depression and psychological measures , multiple measures of social and work functioning , and other domains of health-related quality of life , such as physical functioning , concentration and memory , vitality , bodily pain , sleep , and sexual functioning . RESULTS Follow-up interviews were successfully completed in 94 % of patients at 1 month , 87 % at 3 months , 84 % at 6 months , and 79 % at 9 months . Responses to the 3 SSRIs were comparable on all measures and at all time points . The mean change in the SF-36 Mental Component Summary score at 9 months was + 15.8 in the paroxetine group , + 15.1 in the fluoxetine group , and + 17.4 in the sertraline group . The drugs were also associated with similar incidences of adverse effects and discontinuation rates . CONCLUSIONS The SSRI antidepressants paroxetine , fluoxetine , and sertraline were similar in effectiveness for depressive symptoms as well as multiple domains of health-related quality of life over the entire 9 months of this trial 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 Fluoxetine , a selective serotonin reuptake inhibitor , was compared with mianserin and placebo in a double‐blind study . In total , 81 depressed patients were included . Patients were rated weekly on the Hamilton Depression Rating Scale ( HDRS ) and the Montgomery & Asberg Depression Rating Scale ( MADRS ) . The duration was 6 weeks , and 52 patients completed the study . Significantly more patients on fluoxetine improved than patients on placebo . For mianserin no significant differences were found with either fluoxetine or placebo . Mean HDRS at the end of the study was also statistically significantly lower for fluoxetine , but not for mianserin , than placebo . Subscores of the MADRS showed improved sleep on mianserin at weeks 2 and 3 . Suicidal feelings were reduced to a greater degree on fluoxetine than on mianserin and placebo at weeks 6 and 7 . Fluoxetine  induced weight loss , while patients on mianserin gained weight . Side effects were present in most patients on the two active drugs ; those on fluoxetine experienced nausea and vomiting , and those on mianserin drowsiness
Low-certainty evidence suggests that off-label fluoxetine may decrease weight compared with placebo .
However , low-certainty evidence suggests an increase in the risk for dizziness , drowsiness , fatigue , insomnia and nausea following fluoxetine treatment
BACKGROUND Fluoxetine is a serotonin reuptake inhibitor indicated for major depression .
It is also thought to affect weight control : this seems to happen through appetite changes result ing in decreased food intake and normalisation of unusual eating behaviours .
However , the benefit-risk ratio of this off-label medication is unclear .
OBJECTIVES To assess the effects of fluoxetine for overweight or obese adults .