What constitutes an adequate antidepressant trial for fluoxetine? Mirtazapine versus fluoxetine in the treatment of panic disorder. Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder. Double-blind placebo-controlled trial of fluoxetine in smoking cessation treatment including nicotine patch and cognitive-behavioral group therapy. Fluoxetine versus amineptine in the treatment of outpatients with major depressive disorders. A comparative trial of fluoxetine versus trazodone in outpatients with major depression. Double-blind randomized parallel-group clinical trial of efficacy of the combination fluoxetine plus modafinil versus fluoxetine plus placebo in the treatment of major depression. A double-blind comparison of fluoxetine, imipramine and placebo in outpatients with major depression. Fluoxetine-clonazepam cotherapy for anxious depression: an exploratory, post-hoc analysis of a randomized, double blind study A double-blind, randomized study to provide safety information on switching fluoxetine-treated patients to paroxetine without an intervening washout period. A comparative trial of fluoxetine and amitriptyline in patients with major depressive disorder. Response patterns of depressed outpatients with and without melancholia: a double-blind, placebo-controlled trial of fluoxetine versus placebo. Exploring treatment alternatives: weekly dosing of fluoxetine for the continuation phase of major depressive disorder. Fluoxetine in posttraumatic stress disorder. Efficacy and Safety of Fluoxetine in the Treatment of Patients With Major Depression After First Myocardial Infarction: Findings From a Double-Blind, Placebo-Controlled Trial Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. Differential effects of trimipramine and fluoxetine on sleep in geriatric depression. Moclobemide versus fluoxetine in the treatment of inpatients with major depression. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Controlled comparison of milnacipran and fluoxetine in major depression Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein beta3 subunit as predictors of response to fluoxetine and nortriptyline. Paroxetine in the elderly depressed patient: randomized comparison with fluoxetine of efficacy, cognitive and behavioural effects Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome
One hundred and eight patients with major depression were treated with fluoxetine 20 mg/day for 3 weeks . Patients who failed to respond to this open-label treatment were r and omly assigned either to receive fluoxetine 60 mg/day for 5 weeks or to continue treatment with fluoxetine 20 mg/day for an additional 5 weeks . Both treatment groups demonstrated a statistically significant reduction in depressive symptoms , indicating that continued treatment with low-dose fluoxetine may be as effective as an increase in dose in achieving a favorable clinical outcome Mirtazapine is an antidepressant whose side effect profile differs from that of first-line agents ( selective serotonin reuptake inhibitors ) used in the treatment of panic disorder . The present study compared the effect of mirtazapine and fluoxetine in the treatment of panic disorder in a double-blind , r and omized , flexible-dose trial conducted with out patients . After a 1-week single-blind placebo run-in , 27 patients entered an 8-week double-blind phase in which they were r and omly assigned to treatment with either mirtazapine or fluoxetine . Both groups improved significantly in all but one efficacy measure ( P < or = 0.01 ) . ANOVA showed no significant differences between the two treatment groups in number of panic attacks , Hamilton Anxiety Scale or Sheehan Phobic Scale , whereas measures of patient global evaluation of phobic anxiety were significantly different between groups ( F1,20 = 6.91 , P = 0.016 ) favoring mirtazapine . For the 22 patients who completed the study , the mean daily dose of mirtazapine was 18.3 + /- 1.3 vs 14.0 + /- 1.0 mg for fluoxetine at the endpoint . Weight gain occurred more frequently in the mirtazapine group ( 50 vs 7.7 % , P = 0.04 ) and nausea and paresthesia occurred more often in the fluoxetine group ( P = 0.01 ) . Results suggest that mirtazapine has properties that make it attractive for the treatment of panic disorder OBJECTIVE The authors compared the efficacy and side effects of fluoxetine and placebo in elderly out patients with dysthymic disorder . METHODS Patients were r and omly assigned to fluoxetine ( 20 mg-60 mg/day ) or placebo for 12 weeks in a double-blind trial . RESULTS Of 90 r and omized patients , 71 completed the trial . In the intent-to-treat sample , r and om regression analyses of the Hamilton Rating Scale for Depression ( Ham-D ; 24-item ) and Cornell Dysthymia Rating Scale ( CDRS ) scores at each visit produced significant time x treatment group interactions favoring the fluoxetine group . Analysis of percentage change in Ham-D scores yielded no effect for treatment group , but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group , favoring fluoxetine over placebo . In the intent-to-treat sample , response rates were 27.3 % for fluoxetine and 19.6 % for placebo . In the completer sample , response rates were 37.5 % for fluoxetine and 23.1 % for placebo . CONCLUSION Fluoxetine had limited efficacy in elderly dysthymic patients . The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults , and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients . Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder , and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance Smoking cessation attempts are often complicated by dysphoria/depression , weight gain , craving , and other nicotine withdrawal symptoms . Fluoxetine 's antidepressant and anorectant properties , along with its capacity to attenuate compulsive behavior , suggest that this medication might facilitate smoking cessation treatment . We examined the effect of fluoxetine on smoking cessation in the context of a program that included group cognitive-behavioral therapy ( six weeks ) and transdermal nicotine patch(ten weeks ) . In a double-blind r and omized trial of fluoxetine for smoking cessation , 150 daily smokers were assigned to placebo ( n=48 ) , 20 mg ( n=51 ) , or 40 mg fluoxetine ( n=51 ) . Fluoxetine did not significantly improve smoking cessation rates , either for those with or without major depressive disorder(MDD)histories or elevated current depression . Our results suggest that fluoxetine may moderate withdrawal symptoms , even if that was not manifested in improved smoking cessation rates . Our results , however , clearly favor the use of fluoxetine if weight gain is a major clinical obstacle to smoking cessation 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 effectiveness of fluoxetine as an antidepressant was contrasted with trazodone in a 6-week double-blind trial in 40 patients . The total score on the Hamilton Rating Scale for Depression and the global improvement score on the Clinical Global Impressions scale favored trazodone at the end of 3 weeks of treatment . However , that difference was no longer apparent during the remainder of the study . The authors hypothesize that fluoxetine 20 mg/day may be an ineffective dosage of the drug or that fluoxetine has a slower onset of antidepressant action than does trazodone BACKGROUND There is growing interest in the identification of novel therapeutic agents for the treatment of affective disorders , with modafinil being one promising substance . The purpose of the present investigation was to compare the efficacy of a combination of fluoxetine plus modafinil with that of fluoxetine plus placebo in the treatment of major depression in a 6-week double blind and placebo-controlled trial . METHODS Forty-six adult out patients who met the DSM-IV-TR criteria for major depression participated in the trial . Patients had a baseline Hamilton Rating Scale for depression score of at least 18 . Patients were allocated in a r and om fashion , 23 to fluoxetine 40 mg/day plus modafinil 400 mg/day ( 200 mg bid ) ( morning and evening ) and 23 to fluoxetine 40 mg/day plus placebo . Patients were assessed at baseline and after 1 , 2 , 4 , and 6 weeks after start of medication . RESULTS Forty-four patients completed the trial . Fluoxetine+modafinil and fluoxetine+placebo significantly decreased the Hamilton Rating Scale score for Depression over the trial period . However , the combination of fluoxetine and modafinil was significantly superior over fluoxetine alone in the treatment of symptoms of major depression . The difference between the two treatments was significant as indicated by the effect of group , the between-subjects factor ( df = 1 , F = 4.42 , P = 0.046 ) . There were no significant differences in the two groups in terms of observed side-effects . CONCLUSION These findings suggest modafinil as a well-tolerated and potentially effective agent in combination with fluoxetine in the management of patients with major depression Fluoxetine is the first selective serotonin reuptake inhibitor antidepressant to be marketed in the U.S. In this double-blind trial fluoxetine was compared with imipramine and placebo among 198 out patients with DSM-III major depression , of whom 145 completed at least 2 weeks of active treatment and were evaluated for efficacy . Significantly fewer patients in each active drug group terminated early due to lack of efficacy compared to placebo . Both imipramine and fluoxetine were significantly superior to placebo on most measures . There were no consistently significant differences between the two active drugs although a trend favored imipramine on a number of measures . Fluoxetine was generally well tolerated . Significantly more imipramine than placebo patients terminated early due to side-effects while the fluoxetine-placebo difference was not significant . The results support previous studies which suggest fluoxetine 's superior side-effect profile and the approximate antidepressant equivalence of fluoxetine and TCAs Anxious depression , defined as major depressive disorder ( MDD ) accompanied by high levels of anxiety , seems to be both common and difficult to treat , with antidepressant monotherapy often yielding modest results . We sought to examine the relative benefits of antidepressant-anxiolytic cotherapy versus antidepressant monotherapy for patients with anxious depression versus without anxious depression . We conducted a post-hoc analysis of an existing data set ( N=80 ) , from a 3-week , r and omized , double-blind trial which demonstrated cotherapy with fluoxetine and clonazepam to result in superior efficacy than fluoxetine monotherapy in MDD . The present analysis involved examining whether anxious depression status served as a predictor and moderator of symptom improvement . Anxious depression status was not found to predict symptom improvement , or serve as a moderator of clinical improvement to cotherapy versus monotherapy . However , the advantage in remission rates in favor of cotherapy versus monotherapy was , numerically , much larger for patients with anxious depression ( 32.2 % ) than it was for patients without anxious MDD ( 9.7 % ) . The respective number needed to treat statistic for these two differences in response rates were , approximately , one in three for patients with anxious depression versus one in 10 for patients without anxious depression . The efficacy of fluoxetine-clonazepam cotherapy  compared with fluoxetine monotherapy  was numerically but not statistically enhanced for patients with anxious depression than those without anxious depression BACKGROUND The long elimination half-lives of fluoxetine and norfluoxetine , the active metabolite of fluoxetine , are of potential consequence when alternative antidepressant agents are introduced after the termination of fluoxetine therapy . It is not known whether paroxetine , an antidepressant agent in the same pharmacologic class as fluoxetine , can be substituted for fluoxetine without the need for an intervening washout period . The objective of this trial was to assess the tolerability of an immediate switch from fluoxetine to paroxetine therapy . METHOD Patients who were treated for moderate to moderately severe major depressive disorder ( DSM-III-R 296.2 or 296.3 ) with a stable dose of fluoxetine for a minimum of 6 weeks ' duration were r and omized in a double-blind fashion to one of two treatment groups . One group ( N = 123 ) was started on 20 mg of paroxetine daily the morning after their last dose of fluoxetine , and the other group ( N = 119 ) was started on 20 mg of paroxetine daily following a 2-week placebo-washout period . Patient visits were scheduled at weekly intervals for a total of 4 weeks . Adverse experience monitoring was conducted at each visit . RESULTS There was no difference in the proportion of patients who discontinued prematurely from the trial due to an adverse experience . Eight patients in the immediate-switch group and 6 patients in the placebo-washout group withdrew from the trial in response to an adverse experience ( p = .63 , chi-square ) . The overall profile of adverse experiences was similar in the two treatment groups over the 4-week period . The incidence of adverse experiences in the first 2 weeks following the initiation of paroxetine was generally lower in the group with the intervening 2-week placebo-washout period . CONCLUSION The immediate switch from fluoxetine to paroxetine was as well tolerated as the switch to paroxetine after a 2-week placebo-washout period The efficacy and safety of fluoxetine , a new antidepressant agent , were assessed in a double-blind , parallel , r and omized study of 44 out patients with major depressive disorder . Following a 1-week placebo period , patients were r and omly assigned to either fluoxetine or amitriptyline for a period of 5 weeks . The mean maintenance dosages were 55 mg/day for fluoxetine and 159 mg/day for amitriptyline . Both drugs were effective in relieving the symptoms of depression . The most frequently reported side effects were nausea and nervousness for fluoxetine , and dry mouth , dizziness , and drowsiness for amitriptyline Fluoxetine ( 20 mg/day ) and placebo were compared in 89 outpatient men and women with major depression with ( n = 52 ) or without ( n = 37 ) DSM-III-R melancholia in an 8-week double-blind study to determine predictors of treatment response . Fluoxetine was statistically superior to placebo both within the melancholic subtype and in the total patient group ( all measures ) . Response rate and mean decrease in 17-item Hamilton Depression Rating Scale total score approached statistical significance in favor of fluoxetine-treated melancholic patients compared with fluoxetine-treated non-melancholic patients . There were no statistically significant differences between fluoxetine-treated and placebo-treated non-melancholic patients . Results support DSM-III-R melancholia as a predictor of antidepressant response Antidepressant medications are typically taken on a daily basis owing to both tradition and the pharmacokinetics of these agents . Because fluoxetine and its primary metabolite norfluoxetine have long half-lives and flat dose-response curves , we examined the tolerability of a weekly dose and its equivalence to daily dosing during the continuation phase of treatment for major depressive disorder ( MDD ) . Open-label treatment with 20 mg of fluoxetine daily for 7 weeks began with 114 subjects . Subsequently , 70 subjects who met criteria for response were r and omly assigned in a double-blind design to 1 of 3 treatment groups ( 20 mg of fluoxetine daily [ N = 21 ] , 60 mg of fluoxetine weekly [ N = 28 ] , or placebo [ N = 21 ] ) and followed for 7 weeks . No statistically significant differences were observed in several clinical measures . Tolerability in the 3 groups was similar ; there was no difference in dropout rates or adverse events . Hence , weekly dosing of fluoxetine appears to be well tolerated and possibly as effective as daily dosing in the treatment of MDD . It is proposed that less frequent dosing could potentially benefit patients by enhancing adherence and minimizing the risk of side effects and drug-drug interactions BACKGROUND This study was design ed to establish the efficacy of the serotonin reuptake blocker fluoxetine in the treatment of posttraumatic stress disorder ( PTSD ) . METHOD 64 subjects ( 22 women and 42 men ; 31 veterans and 33 nonveterans ) with PTSD entered a 5-week r and omized double-blind trial comparing fluoxetine ( N = 33 ) and placebo ( N = 31 ) . RESULTS By Week 5 fluoxetine , but not placebo , significantly reduced overall PTSD symptomatology , as assessed by the Clinician-Administered PTSD Scale ( CAPS ) score . Changes were most marked in the arousal and numbing symptom subcategories .  Non-VA patients responded much better than VA patients . Fluoxetine was an effective antidepressant independent of its effects on PTSD . CONCLUSION Fluoxetine is an effective pharmacotherapeutic agent for treating PTSD and its associated features , particularly in patients without chronic treatment histories Objective Depression and hostility are significant risk factors for mortality and morbidity after myocardial infa rct ion ( MI ) . Much research is still needed to identify effective ways to reduce emotional distress in patients with cardiovascular disease . This double-blind , placebo-controlled study investigated the efficacy and safety of the antidepressant fluoxetine in patients with depression after their first MI . Methods Fifty-four patients with major depression after MI were r and omly assigned to receive a flexible-dose regimen of fluoxetine or placebo for the first 9 weeks of a double-blind , placebo-controlled trial . Patients without serious adverse effects who wished to continue participating in the study were given fluoxetine or placebo for an additional 16 weeks . To evaluate the efficacy of fluoxetine , the 17-item Hamilton Depression Rating Scale ( HAMD-17 ) and the Hostility Scale of the 90-item Symptom Check List ( SCL-90 ) were used as primary measures of outcome . To evaluate the safety of fluoxetine , cardiac function was measured before and after treatment with echocardiography and electrocardiography . Results The a priori difference in antidepressive efficacy ( 4-point difference in HAMD-17 scores between the fluoxetine and placebo groups ) was not met . However , the response rate among patients receiving fluoxetine was significantly greater than that among patients receiving placebo at week 25 ( 48 vs. 26 % , p = .05 ) . Among patients with mild depression ( HAMD-17 score ≤21 ) , HAMD-17 scores were significantly different ( p < .05 ) between the fluoxetine and placebo groups at weeks 9 ( by 5.4 points ) and 25 ( by 5.8 points ) . Also , hostility scores at week 25 were significantly reduced among patients receiving fluoxetine ( p = .02 ) . Analysis of electrocardiographic and echocardiographic parameters revealed no decrease in cardiac function as a result of treatment with fluoxetine . Conclusions : Although the overall difference between the fluoxetine and placebo groups was not significant , there was a trend favoring fluoxetine in this relatively small sample . The response rate in the group receiving fluoxetine was comparable with that observed in other studies of patients with cardiovascular disease . In addition , fluoxetine seemed to be particularly effective in patients with mild depression and was associated with a statistically significant reduction in hostility . The results of this study suggest that fluoxetine can be safely used to treat patients with post-MI depression beginning 3 months after the event BACKGROUND A consistent finding in major depression has been a low plasma and red cell folate which has also been linked to poor response to antidepressants . The present investigation was design ed to investigate whether the co-administration of folic acid would enhance the antidepressant action of fluoxetine . METHODS 127 patients were r and omly assigned to receive either 500 microg folic acid or an identical looking placebo in addition to 20 mg fluoxetine daily . All patients met the DSM-III-R criteria for major depression and had a baseline Hamilton Rating Scale ( 17 item version ) score for depression of 20 or more . Baseline and 10-week estimations of plasma folate and homocysteine were carried out . RESULTS Patients receiving folate showed a significant increase in plasma folate . This was less in men than in women . Plasma homocysteine was significantly decreased in women by 20.6 % , but there was no significant change in men . Overall there was a significantly greater improvement in the fluoxetine plus folic acid group . This was confined to women where the mean Hamilton Rating Scale score on completion was 6.8 ( S.D. 4 . 1 ) in the fluoxetine plus folate group , as compared to 11.7 ( S.D. 6 . 7 ) in the fluoxetine plus placebo group (P<0.001).A percentage of 93 . 9 of women , who received the folic acid supplement , showed a good response ( > 50 % reduction in score ) as compared to 61.1 % of women who received placebo supplement ( P<0.005 ) . Eight ( 12.9 % ) patients in the fluoxetine plus folic acid group reported symptoms possibly or probably related to medication , whereas in the fluoxetine plus placebo group 19 ( 29.7 % ) patients reported such symptoms ( P<0.05 ) . LIMITATIONS AND CONCLUSIONS Folic acid is a simple method of greatly improving the antidepressant action of fluoxetine and probably other antidepressants . Folic acid should be given in doses sufficient to decrease plasma homocysteine . Men require a higher dose of folic acid to achieve this than women , but more work is required to ascertain the optimum dose of folic acid 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 Seventy in patients with a DSM-III-R major depression were included in a double-blind , r and omized , clinical trial to compare the efficacy and tolerability of moclobemide versus fluoxetine . After a 3-day placebo run-in phase , treatments were administered for 4 weeks in daily doses of between 300 and 600 mg of moclobemide or 20 to 40 mg of fluoxetine .  Efficacy was measured by the Hamilton Rating Scale for Depression ( HAM-D ) , Clinical Global Impression , and subjective mood ratings ( 45-item self-rating scale ) .  Fifty-three patients ( mean age , 40 years ; 22 men , 31 women ) completed the 4-week treatment . Changes between end of treatment and baseline did not differ between both study drugs . The HAM-D responder rate ( 50 % improvement from baseline ) was 59 % in the moclobemide group and 58 % in the fluoxetine group after 4 weeks . Moclobemide , however , acted therapeutically faster than fluoxetine . After 1 week of treatment , the HAM-D scores were significantly lower in patients on moclobemide than in those on fluoxetine ( p < 0.005 ) . The earlier efficacy of moclobemide after 1 week was also detected by the patients ' subjective mood ratings ( p < 0.02 ) . There were no differences between moclobemide and fluoxetine regarding tolerability ratings . These data suggest that both agents have a similar efficacy and tolerability but that moclobemide has an earlier onset of antidepressive action BACKGROUND Depression is a major cause of morbidity and mortality in children and adolescents . To date , r and omized , controlled , double-blind trials of antidepressants ( largely tricyclic agents ) have yet to reveal that any antidepressant is more effective than placebo . This article is of a r and omized , double-blind , placebo-controlled trial of fluoxetine in children and adolescents with depression . METHODS Ninety-six child and adolescent out patients ( aged 7 - 17 years ) with nonpsychotic major depressive disorder were r and omized ( stratified for age and sex ) to 20 mg of fluoxetine or placebo and seen weekly for 8 consecutive weeks . R and omization was preceded by 3 evaluation visits that included structured diagnostic interviews during 2 weeks , followed 1 week later by a 1-week , single-blind placebo run-in . Primary outcome measurements were the global improvement of the Clinical Global Impressions scale and the Children 's Depression Rating Scale -- Revised , a measure of the severity depressive symptoms . RESULTS Of the 96 patients , 48 were r and omized to fluoxetine treatment and 48 to placebo . Using the intent to treat sample , 27 ( 56 % ) of those receiving fluoxetine and 16 ( 33 % ) receiving placebo were rated " much " or " very much " improved on the Clinical Global Impressions scale at study exit ( chi 2 = 5.1 , df = 1 , P = .02 ) . Significant differences were also noted in weekly ratings of the Children 's Depression Rating Scale -- Revised after 5 weeks of treatment ( using last observation carried forward ) . Equivalent response rates were found for patients aged 12 years and younger ( n = 48 ) and those aged 13 years and older ( n = 48 ) . However , complete symptom remission ( Children 's Depression Rating Scale -- Revised < or = 28 ) occurred in only 31 % of the fluoxetine-treated patients and 23 % of the placebo patients . CONCLUSION Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent out patients with severe , persistent depression . Complete remission of symptoms was rare 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 In 169 depressed patients r and omized to treatment with either fluoxetine or nortriptyline  , we examined whether polymorphisms of the serotonin transporter and the G protein beta3 subunit influenced response to these antidepressants . For depressed patients under the age of 25 yr the T allele of the G protein beta3 subunit was associated with a markedly poorer response to nortriptyline , while serotonin transporter polymorphisms did not predict antidepressant response . However , in patients 25 yr or older , the G protein beta3 polymorphisms did not predict antidepressant response , while the s , s genotype of the serotonin transporter was associated with a poorer response to both fluoxetine and nortriptyline . These differential pharmacogenetic predictors of antidepressant response by age , may provide clues to underst and ing the discontinuities in pharmacological responsiveness of child/adolescent and adult depressive disorders The efficacy of paroxetine and fluoxetine and their effects on cognitive and behavioural function were compared in a 6 week , double-blind , r and omized study of 106 elderly depressed patients ( aged 61 to 85 years ) .  Antidepressant efficacy was assessed using the Hamilton depression rating scale ( HAMD ) , Montgomery-Asberg Depression Rating Scale ( MADRS ) and Clinical Global Impression ( CGI ) scale . The S and oz Clinical Assessment Geriatric scale ( SCAG ) , the Mini-Mental State Examination ( MMSE ) , and HAMD cognitive factor scores were used to assess cognitive and behavioural function . Paroxetine demonstrated comparable efficacy to fluoxetine in the treatment of elderly depressed patients , but at the end of treatment , there was a significantly higher proportion of responders to paroxetine than to fluoxetine . Both treatments produced improvements in all measures of cognitive and behavioural function , but paroxetine was significantly superior to fluoxetine from Week 3 , indicating a possible early effect . There was no difference between the two agents in either the tolerability or safety of treatment BACKGROUND No somatic treatment has been found to be effective for chronic fatigue syndrome ( CFS ) . Antidepressant therapy is commonly used . Fluoxetine is recommended in preference to tricyclic agents because it has fewer sedative and autonomic nervous system effects . However , there have been no r and omised , placebo-controlled , double-blind studies showing the effectiveness of antidepressant therapy in CFS . We have carried out such a study to assess the effect of fluoxetine in depressed and non-depressed CFS patients . METHODS In this r and omised , double-blind study , we recruited 44 patients to the depressed CFS group , and 52 to the non-depressed CFS group . In each group participants were r and omly assigned to receive either fluoxetine ( 20 mg once daily ) or placebo for 8 weeks . The effect of fluoxetine was assessed by question naires , self-observation lists , st and ard neuropsychological tests , and a motion-sensing device ( Actometer ) , which were applied on the day treatment started and on the last day . FINDINGS The two groups were well matched in terms of age , sex distribution , employment and marital status , and duration of CFS . There were no significant differences between the placebo and fluoxetine-treated groups in the change during the 8-week treatment period for any dimension of CFS . There was no change in subjective assessment s of fatigue , severity of depression , functional impairment , sleep disturbances , neuropsychological function , cognitions , or physical activity in the depressed or the non-depressed subgroup . INTERPRETATION Fluoxetine in a 20 mg daily dose does not have a beneficial effect on any characteristic of CFS . The lack of effect of fluoxetine on depressive symptoms in CFS suggests that processes underlying the presentation of depressive symptoms in CFS may differ from those in patients with major depressive disorder
A metaregression analysis indicated that , after adjusting for possible confounders , studies where fluoxetine was the experimental agent were positively associated with treatment effect , indicating a significant advantage for fluoxetine .
The evidence that the outcome of fluoxetine trials varied according to whether this drug was used as a new compound or a reference one suggests the presence of bias
The present study investigated whether the outcome of r and omized clinical trials study ing fluoxetine favored fluoxetine , where this was the experimental agent , and favored comparator antidepressants in trials where fluoxetine was the reference agent .