A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Compliance with antidepressant medication in the treatment of major depressive disorder in primary care: a randomized comparison of fluoxetine and a tricyclic antidepressant. A multicentre open trial of fluoxetine in depressed out-patients in Belgium. Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study. A double-blind comparison of fluoxetine, imipramine and placebo in outpatients with major depression. A Naturalistic Long-Term Comparison Study of Selective Serotonin Reuptake Inhibitors in the Treatment of Panic Disorder Is Baseline Agitation a Relative Contraindication for a Selective Serotonin Reuptake Inhibitor: A Comparative Trial of Fluoxetine Versus Imipramine Prophylactic efficacy of fluoxetine, escitalopram, sertraline, paroxetine, and concomitant psychotherapy in major depressive disorder: Outcome after long-term follow-up A comparative trial of a new antidepressant, fluoxetine. 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 A Canadian multicenter, double-blind study of paroxetine and fluoxetine in major depressive disorder. Similar effectiveness of paroxetine, fluoxetine, and sertraline in primary care: a randomized trial. Maintenance Therapy With Fluoxetine in Posttraumatic Stress Disorder: A Placebo-Controlled Discontinuation Study Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial. A double-blind controlled comparison of fluoxetine and lofepramine in major depressive illness A randomized double-blind clinical trial on analgesic efficacy of fluoxetine for persistent somatoform pain disorder
OBJECTIVE To determine the relative cost-effectiveness of three classes of antidepressants : tricyclic antidepressants ( TCAs ) , selective serotonin reuptake inhibitors ( SSRIs ) , and the modified TCA lofepramine , as first choice treatments for depression in primary care . DESIGN Open , pragmatic , controlled trial with three r and omised arms and one preference arm . Patients were followed up for 12 months . SETTING UK primary care : 73 practice s in urban and rural areas in Engl and . PARTICIPANTS Patients with a new episode of depressive illness according to GP diagnosis . INTERVENTIONS Patients were r and omised to receive a TCA ( amitriptyline , dothiepin or imipramine ) , an SSRI ( fluoxetine , sertraline or paroxetine ) or lofepramine . Patients or GPs were able to choose an alternative treatment if preferred . MAIN OUTCOME MEASURES At baseline the Clinical Interview Schedule , Revised ( CIS-R PROQSY computerised version ) was administered to establish symptom profiles . Outcome measures over the 12-month follow-up included the Hospital Anxiety and Depression Scale self-rating of depression ( HAD-D ) , CIS-R , EuroQol ( EQ-5D ) for quality of life , Short Form ( SF-36 ) for generic health status , and patient and practice records of use of health and social services . The primary effectiveness outcome was the number of depression-free weeks ( HAD-D less than 8 , with interpolation of intervening values ) and the primary cost outcome total direct NHS costs . Quality -adjusted life-years ( QALYs ) were used as the outcome measure in a secondary analysis . Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were computed . Estimates were bootstrapped with 5000 replications . RESULTS In total , 327 patients were r and omised . Follow-up rates were 68 % at 3 months and 52 % at 1 year . Linear regression analysis revealed no significant differences between groups in number of depression-free weeks when adjusted for baseline HAD-D. A higher proportion of patients r and omised to TCAs entered the preference arm than those allocated to the other choices . Switching to another class of antidepressant in the first few weeks of treatment occurred significantly more often in the lofepramine arm and less in the preference arm . There were no significant differences between arms in mean cost per depression-free week . For values placed on an additional QALY of over 5000 pounds , treatment with SSRIs was likely to be the most cost-effective strategy .  TCAs were the least likely to be cost-effective as first choice of antidepressant for most values of a depression-free week or QALY respectively , but these differences were relatively modest . CONCLUSIONS When comparing the different treatment options , no significant differences were found in outcomes or costs within the sample , but when outcomes and costs were analysed together , the result ing cost-effectiveness acceptability curves suggested that SSRIs were likely to be the most cost-effective option , although the probability of this did not rise above 0.6 . Choosing lofepramine is likely to lead to a greater proportion of patients switching treatment in the first few weeks . Further research is still needed on the management of depressive illness in primary care . This should address areas such as the optimum severity threshold at which medication should be used ; the feasibility and effectiveness of adopting structured depression management programmes in the UK context ; the importance of factors such as physical co-morbidity and recent life events in GPs ' prescribing decisions ; alternative ways of collecting data ; and the factors that give rise to many patients being reluctant to accept medication and discontinue treatment early 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 OBJECTIVE Many cl aims have been made for superior compliance with selective serotonin reuptake inhibitors ( SSRIs ) compared with tricyclic antidepressants , but to date meta-analyses have not confirmed reduced dropouts in r and omized controlled trials . The authors used a r and omized study design to evaluate differential compliance with antidepressant medications in a primary care setting . METHOD A total of 152 patients treated in 10 primary care practice s in the United Kingdom were included in a r and omized , open-label , parallel-group study of fluoxetine and dothiepin at therapeutic doses for 12 weeks . Compliance was assessed by using pill count , patient question naires , and the Medication Event Monitoring System . RESULTS The level of compliance with fluoxetine was numerically higher than the level of compliance with dothiepin on all three primary outcome measures , although the differences were not significant . In a secondary analysis using data from the Medication Event Monitoring System , both a survival analysis for length of time without a gap in medicine taking and a derived compliance index showed a significant advantage to fluoxetine . Patients in the fluoxetine group reported superior response on the health transition scale of the 36-item Short-Form Health Survey Question naire and numerically greater improvement on the Hamilton Depression Rating Scale . In both treatment arms patients with a superior compliance index were more likely to have improved in Hamilton depression scale scores by the last study visit . CONCLUSIONS This study supports recent meta-analyses of SSRIs versus tricyclic antidepressants in finding no significant differences in crude indices of compliance between fluoxetine and dothiepin , despite marked differences in side effect profile and dose regimen . However , both a survival analysis and a new measure that takes account of prolonged periods of noncompliance distinguished between the treatments and was associated with improvement in both groups Fluoxetine hydrochloride ( ProzacR , Lilly ) , a new antidepressant that specifically inhibits serotonin reuptake was evaluated in an open comparative trial performed in 8 Belgian centres over a period of 9 months . Seventy-six out patients were enrolled of which 66 were evaluable . Thirty-six patients received an 8 week fluoxetine treatment and 31 patients received tricyclic antidepressants ( TCA ) . Patients from both treatment groups were evaluated for safety and the fluoxetine treated group of patients was assessed for efficacy . On the Hamilton Depression Scale , the mean score dropped from 26.4 to 7.0 after 8 weeks ( p less than 0.0001 ) . The Clinical and Patient 's Global Impression scores showed a similar evolution . Patients treated with fluoxetine tended to report fewer side-effects than the TCA treated group . Therefore fluoxetine can be regarded as an efficient antidepressant which is at least as well tolerated as TCAs OBJECTIVE Various classes of antidepressant medications generally induce remission of major depressive disorder  in only about one-third of patients . In a previous study using mirtazapine or paroxetine alone or in combination from treatment initiation , the rate of patients who remitted within a 6-week period was twice that of patients using either drug alone . In this double-blind study , the authors sought to produce evidence for the superiority of different combinations of antidepressant drugs from treatment initiation . METHOD Patients ( N=105 ) meeting DSM-IV criteria for major depressive disorder were r and omly assigned to receive , from treatment initiation , either fluoxetine monotherapy ( 20 mg/day ) or mirtazapine ( 30 mg/day ) in combination with fluoxetine ( 20 mg/day ) , venlafaxine ( 225 mg/day titrated in 14 days ) , or bupropion ( 150 mg/day ) for 6 weeks . The primary outcome measure was the Hamilton Depression Rating Scale ( HAM-D ) score . RESULTS The overall dropout rate was 15 % , without notable differences among the four groups . Compared with fluoxetine monotherapy , all three combination groups had significantly greater improvements on the HAM-D. Remission rates ( defined as a HAM-D score of 7 or less ) were 25 % for fluoxetine , 52 % for mirtazapine plus fluoxetine , 58 % for mirtazapine plus venlafaxine , and 46 % for mirtazapine plus bupropion . Among patients who had a marked response , double-blind discontinuation of one agent produced a relapse in about 40 % of cases . CONCLUSIONS The combination treatments were as well tolerated as fluoxetine monotherapy and more clinical ly effective . The study results , which add to a growing body of evidence , suggest that use of antidepressant combinations from treatment initiation may double the likelihood of remission compared with use of a single medication 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 Objectives : Selective serotonin reuptake inhibitors ( SSRIs ) are currently considered as the first drug of choice in the treatment of panic disorder ( PD ) . The aim of this long-term , naturalistic comparison study was to compare 4 SSRIs with respect to tolerability and treatment outcome of PD . Outcome measures included relapse rates and adverse effects . Methods : Two hundred patients with PD were enrolled in our study . All subjects met DSM-IV criteria for PD or PD with agoraphobia ( PDA ) . All patients were assigned to receive SSRI monotherapy for 12 months with either citalopram ( n = 50 ) , fluoxetine ( n = 50 ) , fluvoxamine ( n = 50 ) , or paroxetine ( n = 50 ) in a r and omized , nonblinded fashion . Both the treating psychiatrist and the patients were not blind to the assigned treatment , but the clinician raters were blind to the study medication . The study design allowed for assignment of a particular SSRI as indicated according to the clinical judgment of the study psychiatrists . The Panic Self- Question naire , which is a self-report scale , was administered at baseline and then once per month during the duration of the 12-month study . The visual analog scale and the Clinical Global Impression Scale were administered at baseline and then once per month during the period of the study . Reports of sexual dysfunction were assessed using a nonstructured clinical interview at monthly visits . The body weight of study subjects was measured at baseline , and then at the 12th month visit end point . Results : Of 200 patients who entered the study , 127 patients ( 63.5 % ) completed the full 12-month protocol . Retention rates were highest for paroxetine ( 76 % [ 38/50 ] ) , intermediate for citalopram ( 68 % [ 34/50 ] ) and fluvoxamine ( 60 % [ 30/50 ] ) , and lowest for fluoxetine ( 50 % [ 25/50 ] ) . Patients who completed the 12-month protocol responded favorably to the study treatment . The paroxetine and the citalopram groups had significantly lower rates of panic symptoms as measured at visits on weeks 4 and 8 . At visits on months 3 , 6 , 9 , and 12 , however , there were no statistically significant differences between the 4 groups in relapse rates ( defined as the occurrence of 1 or more panic attacks during the previous week of treatment ) ( F1,127 = 0.17 ; P = 0.13 [ not statistically significant ] ) . At the 12th month end point , patients in all 4 treatment groups had a statistically significant increase in body weight . Body weight among the study population increased by 6.1 + 4.9 kg from a mean weight of 72.4 + 7.3 kg at the onset of treatment . Reports of sexual adverse effects at the 12th month visit were similar in the citalopram , fluoxetine , and paroxetine groups , but the fluvoxamine patient group reported fewer sexual adverse effects at the 12th month visit . Conclusions : Most of our PD patients responded well to 12-month treatment with either citalopram , fluoxetine , fluvoxamine , or paroxetine , and the overall response rate was equal after the first 4 weeks of treatment . Although patients treated with paroxetine had the lowest dropout rates during the initiation phase , they had the highest rate of adverse effects as measured at the 12th month visit . Conversely , patients in the fluvoxamine group had the highest dropout rate ( which was primarily caused by adverse effects in the initiation phase of treatment . ) ; however , patients who were able to tolerate fluvoxamine throughout the full course of the study were observed to have lower rates of sexual dysfunction and weight gain compared with patients treated with the other agents . Overall , when measured at the 12th month visit , monotherapy with paroxetine and citalopram was associated with a higher rate of sexual adverse effects than was treatment with fluoxetine or fluvoxamine . In addition , monotherapy with paroxetine , citalopram , and fluoxetine seemed to cause more weight gain than did treatment with fluvoxamine A common presentation for major depression includes psychomotor agitation . However , this subtype has been the infrequent subject of controlled investigation during depression trials . Yet , the subcategorization of agitated depression has historically been associated with the belief that older , sedating compounds have a superior risk : benefit profile . In the 8-week , double-blind , r and omized , parallel trial , 124 subjects with Research Diagnostic Criteria -compatible agitated depression were r and omized to either imipramine ( IMI ) or fluoxetine ( FLU ) . Both compounds proved to be similarly effective as measured by change in HAM-D17 , HAM-D17 response , and HAM-D17 remission rates . Similar comparability was seen in secondary measures of agitation , anxiety , suicidality , and global impressions . However , of note , a statistically significant difference in early discontinuations because of intolerable adverse events emerged . Whereas 43.5 % of IMI subjects discontinued early , only 9.7 % of FLU subjects ( p < 0.001 ) did . Significantly more central nervous system events characterized the IMI than the FLU subgroup ( IMI , 24.2 % , vs. FLU , 6.5 % ; p = 0.006 ) . In conclusion , among subjects with major depression , subtype agitated , the risk : benefit profile favored FLU over IMI . This was driven by the superior tolerance of FLU . No evidence emerged in support of the clinical hypothesis that a “ sedating ” agent is the treatment of choice for this group . The results are important when striving to maximize compliance with pharmacotherapy in order to minimize recidivism and associated psychological and economic morbidity . ( J Clin Psychopharmacol 1994;14:385–391 The acute efficacy of selective serotonin reuptake inhibitors ( SSRIs ) in the treatment of major depressive disorder ( MDD ) is well established ; however their role in longer-term prevention of recurrence remains unconfirmed . This study aims at examining : the prophylactic efficacy of four commonly used SSRIs in MDD in a naturalistic setting with long-term follow-up , the effect of concomitant cognitive behavioral therapy ( CBT ) , and the predictors of outcome . In a prospect i ve cohort study , 387 patients who either remitted or responded following treatment with four different SSRIs-fluoxetine , escitalopram , sertraline and paroxetine-were  followed up over several years . During an average follow-up period of 34.5 months , 76.5 % of patients experienced MDD recurrence . Escitalopram and fluoxetine showed a numerically higher prophylactic efficacy than paroxetine and sertraline but the difference was statistically insignificant . The prophylactic efficacy for SSRI-only treatment was limited , with a recurrence rate of 82.0 % , compared to 59.0 % of patient recurrence rate in concomitant Cognitive Behavioral Therapy ( CBT ) . The relatively small size of the CBT group and the lack of r and omization may undermine the extrapolation of its findings to clinical practice . Nevertheless , the study preliminary data may help in defining the clinical utility of antidepressants and CBT in the prophylaxis from MDD recurrence A double-blind clinical trial was undertaken to evaluate clinical efficacy and safety of fluoxetine in comparison with the st and ard tricyclic antidepressant , imipramine , in the treatment of depressive illness . The opportunity was taken to compare the relationship of some st and ard measures of depressive illness , two observer based -- Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale ( Montgomery and Asberg , 1979)-- and a self-rating scale -- Levine Pilowsky Depression question naire ( Pilowsky et al. , 1969 ) 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 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 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 Abstract : The effect of fluoxetine ( FLU ) in posttraumatic stress disorder was studied in a one-year trial . Subjects received open-label treatment for 6 months , followed by double-blind r and omized treatment with FLU or placebo ( PBO ) for 6 months . Rates of relapse were compared using the Clinical Global Impressions of Improvement .  One hundred twenty-three subjects entered open-label treatment , of whom 114 returned at least once . Sixty-two subjects were r and omized to receive FLU or PBO , of whom 57 returned at least once and were analyzed . The dose of FLU ranged from 10 to 60 mg/d ; at r and omization , mean doses were 48.6 and 42.1 mg for FLU and PBO groups . Rates of relapse were 22 % for FLU versus 50 % for PBO ( P = 0.02 ) , and time to relapse on FLU was longer than for PBO ( P = 0.02 , log-rank statistic ) . The odds ratio for relapse on PBO relative to FLU was 3.50 . No significant differences were found on other measures . Fluoxetine was well tolerated during double-blind treatment BACKGROUND Antidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters . We wished to investigate whether genetic variation could be used to target or personalise treatment , in a comparison of selective serotonin reuptake inhibitors ( SSRIs ) with noradrenaline reuptake inhibitors ( NARIs ) . AIMS To test the hypothesis that patients homozygous for the long ( insertion ) polymorphism of the serotonin transporter ( 5-HTTLPR ) have an increased response to SSRI antidepressants but not to NARI antidepressants . METHOD In an individually r and omised , parallel-group controlled trial , people meeting criteria for a depressive episode who were referred by their general practitioner were r and omised to receive either citalopram ( an SSRI ) or reboxetine ( an NARI ) . R and omisation was by means of a remote automated system accessed by telephone . The main outcome was depressive symptoms , measured by Beck Depression Inventory ( BDI ) total score 6 weeks after r and omisation . The trial was registered with the International St and ard R and omised Controlled Trials Number registry ( IS RCT N31345163 ) . RESULTS Altogether 298 participants were r and omised to receive citalopram and 303 were r and omised to reboxetine . At 6 weeks follow-up , complete data were available for 258 participants taking citalopram and 262 taking reboxetine . We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment . The interaction term for BDI score at 6 weeks was 0.50 ( 95 % CI -2.04 to 3.03 , P = 0.70 ) , which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype . CONCLUSIONS It is unlikely that the 5-HTTLPR polymorphism alone will be clinical ly useful in predicting response to antidepressants in people with depression One hundred and eighty three patients with DSM-III-R major depressive illness were allocated r and omly to treatment with one of two new generation antidepressants , fluoxetine and lofepramine . Both patient groups had significantly lower mean scores on the Hamilton Depression Rating Scale ( HDRS ) 6 weeks after entry to the trial ( p < 0.001 ) , but there were no differences between the groups , either at baseline or after 6 weeks , in total HRDS score or in subscores for anxiety or suicidality . Anticholinergic side effects were commoner with lofepramine ; adverse effects were on the whole mild and few patients dropped out because of them . This study does not support previous cl aims of specific adverse effects of fluoxetine on anxiety and suicidality OBJECTIVES To verify the efficacy and safety of fluoxetine in treating patients with persistent somatoform pain disorder ( PSPD ) . METHODS In this 8-week , r and omized double-blind placebo-controlled study , 80 patients with an ICD-10 diagnosis of PSPD were r and omly assigned to receive 20 mg fluoxetine or a placebo . Several psychological scales including Medical Outcomes Study Pain Measures ( MOSPM ) , Hamilton Depression Scale-17 items ( HAMD(17 ) ) and Treatment Emergent Symptom Scale ( TESS ) were used to assess analgesic efficacy and safety of fluoxetine , and the possible analgesic mechanism of fluoxetine was preliminarily analyzed . All data were analyzed by SPSS11.5 with t-test , one-way ANOVA and a mixed-effects model repeated measures analysis . Intent-to-treat ( ITT ) analysis was performed and the last observation carry forward ( LOCF ) was used for missing values . RESULTS There was a significant difference of MOSPM total score between the fluoxetine and placebo group after 2 weeks of treatment . The analgesic effect of fluoxetine was related with treatment time , and depressive patients showed a better analgesic effect than non-depressive patients . An adverse effect of fluoxetine was scarcely found . CONCLUSIONS Fluoxetine has a better analgesic effect than a placebo in treating persistent somatoform pain disorder , and is considered a safe treatment ; its analgesic effect may be related to an antidepressant effect
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 .