Is anxious-agitated major depression responsive to fluoxetine? A double-blind comparison with amitriptyline. Differential effects of trimipramine and fluoxetine on sleep in geriatric depression. Venlafaxine compared with fluoxetine in outpatients with depression and concomitant anxiety. Fluoxetine versus trazodone in the treatment of outpatients with major depression. Comparative efficacy and safety of nortriptyline and fluoxetine in the treatment of major depression: a clinical study. A review of multicenter controlled studies of fluoxetine vs. imipramine and placebo in outpatients with major depressive disorder. A double-blind controlled comparison of fluoxetine and lofepramine in major depressive illness. A comparison of fluoxetine, imipramine, and placebo in patients with major depressive disorder. A comparison of fluoxetine imipramine and placebo in patients with bipolar depressive disorder. Fluoxetine in depressed patients: a comparison with imipramine. A comparison of fluoxetine and imipramine in the treatment of outpatients with major depressive disorder. Fluoxetine versus nomifensine in outpatients with neurotic or reactive depressive disorder. Efficacy and safety of tianeptine in the treatment of depressive disorders in comparison with fluoxetine. Gender differences in the efficacy of fluoxetine and maprotiline in depressed patients: a double-blind trial of antidepressants with serotonergic or norepinephrinergic reuptake inhibition profile. Fluoxetine, a selective serotonin uptake inhibitor, for the treatment of outpatients with major depression. Clinical and economic comparison of sertraline and fluoxetine in the treatment of depression. A 6-month double-blind study in a primary-care setting in France. Moclobemide versus fluoxetine for double depression: a randomized double-blind study. A double-blind multi-centre trial of fluoxetine and dothiepin in major depressive illness. South Wales Antidepressant Drug Trial Group. Fluoxetine compared with imipramine in the treatment of inpatient depression. A multicenter trial. A double-blind, randomized, group-comparative study of the tolerability and efficacy of 6 weeks' treatment with mirtazapine or fluoxetine in depressed Chinese patients. Fluoxetine and desipramine in major depressive disorder. Fluoxetine versus imipramine. Fluoxetine versus amineptine in the treatment of outpatients with major depressive disorders. Fluoxetine versus phenelzine in atypical depression. A comparison of fluvoxamine and fluoxetine in the treatment of major depression. Effectiveness of fluoxetine and doxepin in treatment of melancholia in depressed patients. Paroxetine and fluoxetine effects on mood and cognitive functions in depressed nondemented elderly patients. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. Increased remission rates with venlafaxine compared with fluoxetine in hospitalized patients with major depression and melancholia. A comparison of nefazodone and fluoxetine on mood and on objective, subjective, and clinician-rated measures of sleep in depressed patients: a double-blind, 8-week clinical trial. A double-blind parallel study to compare fluoxetine with doxepin in the treatment of major depressive disorders. Mirtazapine: efficacy and tolerability in comparison with fluoxetine in patients with moderate to severe major depressive disorder. Mirtazapine-Fluoxetine Study Group. Fluoxetine vs. clomipramine in depressed patients: a controlled multicentre trial. Comparative effects of fluoxetine and amitriptyline on cardiac function. Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. Venlafaxine XR 360 Study Group. Tianeptine and fluoxetine in major depression: a 6-week randomised double-blind study. [The study of the efficacy of fluoxetine versus tianeptine in the treatment of elderly depressed patients followed in general practice]. A double-blind comparison of the efficacy and safety of milnacipran and fluoxetine in depressed inpatients. Compliance with antidepressant medication in the treatment of major depressive disorder in primary care: a randomized comparison of fluoxetine and a tricyclic antidepressant. A double-blind study of fluoxetine and imipramine in major depression. A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients. Hypericum perforatum versus fluoxetine in the treatment of mild to moderate depression. Is baseline agitation a relative contraindication for a selective serotonin reuptake inhibitor: a comparative trial of fluoxetine versus imipramine. A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression. Fluoxetine 40 mg vs maprotiline 75 mg in the treatment of out-patients with depressive disorders. A comparative clinical trial of fluoxetine, mianserin and placebo in depressed outpatients. A multicentre double blind trial of fluoxetine versus amitriptyline in the treatment of depressive illness. Fluoxetine versus clomipramine in major depressive disorders. A double-blind, randomized, placebo-controlled trial of once-daily venlafaxine extended release (XR) and fluoxetine for the treatment of depression. A comparative trial of a new antidepressant, fluoxetine. Reboxetine: a double-blind comparison with fluoxetine in major depressive disorder. Moclobemide versus fluoxetine for a major depressive episode. Efficacy and response time to sertraline versus fluoxetine in the treatment of unipolar major depressive disorder. Moclobemide versus fluoxetine for major depressive episodes. Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine. The impact of antidepressants on sleep and anxiety: a comparative study of fluoxetine and dothiepin using the Leeds Sleep Evaluation Questionnaire. Randomized, double-blind comparison of venlafaxine and fluoxetine in outpatients with major depression. Fluoxetine compared with amitriptyline in elderly depression: a controlled clinical trial. Fluoxetine versus trazodone in depressed geriatric patients. Antidepressant efficacy and quality of life in depression: a double-blind study with moclobemide and fluoxetine. A comparison of fluoxetine and amitriptyline in the treatment of major depression. Double-blind comparison of bupropion and fluoxetine in depressed outpatients. Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder. A randomized, open-label comparison of venlafaxine and fluoxetine in depressed outpatients. Fluvoxamine versus fluoxetine in major depressive episode: a double-blind randomised comparison. A double-blind comparison of moclobemide and fluoxetine in the treatment of depressive disorders. The SSRIs drug Fluoxetine, but not the noradrenergic tricyclic drug Desipramine, improves memory performance during acute major depression. A comparative trial of fluoxetine versus trazodone in outpatients with major depression. A double-blind comparative study of fluoxetine and dothiepin in the treatment of depression in general practice. Acute efficacy of fluoxetine versus sertraline and paroxetine in major depressive disorder including effects of baseline insomnia. A double-blind comparison of venlafaxine and fluoxetine for treatment of major depression in outpatients. [Double-blind study of mianserin and fluoxetine in ambulatory therapy of depressed patients]. A double-blind comparison of fluoxetine, imipramine and placebo in outpatients with major depression. A double-blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients. Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Moclobemide versus fluoxetine in the treatment of inpatients with major depression. Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression. Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression. Amisulpride versus fluoxetine in patients with dysthymia or major depression in partial remission: a double-blind, comparative study. A controlled comparison of fluoxetine and amitriptyline in depressed out-patients. Comparative efficacy of sertraline vs. fluoxetine in patients age 70 or over with major depression. Fluoxetine in endogenous depression and melancholia versus clomipramine. Double-blind comparative trials of fluoxetine and doxepin in geriatric patients with major depressive disorder. A comparative trial of fluoxetine and amitriptyline in patients with major depressive disorder. The efficacy and acceptability of amineptine versus fluoxetine in major depression. Double-blind controlled study on the clinical efficacy and safety of fluoxetine vs clomipramine in the treatment of major depressive disorders. A Canadian multicenter, double-blind study of paroxetine and fluoxetine in major depressive disorder. A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression. A double-blind multicenter trial comparing sertraline and fluoxetine in outpatients with major depression. [Efficacy and safety of fluoxetine versus clomipramine in ambulatory patients with a depressive syndrome in a clinical trial with private practitioners]. A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients. Fluoxetine vs amitriptyline in the treatment of depressed out-patients. Double-blind comparison of fluoxetine and nortriptyline in the treatment of moderate to severe major depression. Compliance in depressed patients treated with fluoxetine or amitriptyline. Belgian Compliance Study Group. Reboxetine, a new noradrenaline selective antidepressant, is at least as effective as fluoxetine in the treatment of depression. A double-blind parallel study comparing fluoxetine with imipramine in the treatment of atypical depression. A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. The Venlafaxine French Inpatient Study Group. A randomized, double-blind study of fluoxetine and maprotiline in the treatment of major depression. Fluoxetine in major depression: efficacy, safety and effects on sleep polygraphic variables. Controlled comparison of milnacipran and fluoxetine in major depression. Moclobemide versus fluoxetine in the treatment of major depressive disorder in adults. Fluoxetine versus amitriptyline in the treatment of major depression with associated anxiety (anxious depression): a double-blind comparison.
Whether fluoxetine (FX) is effective in the treatment of anxious depression is still debated. In the present study, after one week of placebo (single blind), 142 outpatients affected by major depression with relevant anxiety and agitation were randomly assigned (double blind) to either FX (20 mg/day) (n. 67) or amitriptyline (AM) (daily dose: 115+/-39.2mg) (n.75) for a period of 10 weeks. Between groups, the mean score of Hamilton Rating Scale for Depression (HRSD) was significantly different only after 3 weeks of treatment (AM 14.7+/-5.7 vs FX 17.3+/-6.2 (p = 0.02), whereas at the end of the trial it was similar (AM 8.15+/-6.9; FX 8.96+/-6.6). At each visit, no significant difference between groups was found regarding the scores of the HRSD items "psychic anxiety", "somatic anxiety", "agitation". Furthermore, the FIX treatment did not increase the scores of the items "suicide", "psychic anxiety", "somatic anxiety", "agitation" and "insomnia". These findings suggest that patients affected by major depression with anxiety and/or agitation were effectively and safely treated with FX without increasing risks. 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 resulting 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 aim of this double-blind study was to compare the efficacy and safety of venlafaxine vs. fluoxetine in the treatment of patients with depression and anxiety. A total of 146 moderately depressed patients with associated anxiety were randomized to receive 75 mg/d venlafaxine or 20 mg/d fluoxetine for 12 wk. Dose increases were permitted after 2 wk of treatment, to 150 mg/d venlafaxine and 40 mg/d fluoxetine, to optimize response. At the final visit, a statistically significantly greater efficacy of venlafaxine over fluoxetine was observed on depressive symptoms and concomitant anxiety, and 75.0 and 50.7% of patients administered venlafaxine and fluoxetine, respectively, showed an overall response. A sustained response (for at least 2 wk), present at the end of the study was achieved in 57.8 and 43.3% of patients in the venlafaxine and fluoxetine groups, respectively, and at the final visit, 59.4 and 40.3% of patients, respectively, were in remission (virtually asymptomatic). Dose increases were required by a greater percentage of patients in the fluoxetine group (52.9%), than in the venlafaxine group (37.1%), and in those patients whose dose was increased, a higher efficacy was again observed with venlafaxine. Venlafaxine and fluoxetine were well tolerated, with the most frequently experienced adverse events being nausea and headache. Fewer patients in the venlafaxine group than in the fluoxetine group reported at least one adverse event (55.7 and 67.1% patients, respectively). Venlafaxine therefore proved to be significantly more effective than fluoxetine in improving depressive symptoms and concomitant anxiety. Fluoxetine and trazodone were compared in a double-blind, randomized, parallel, 6-week trial in 43 outpatients with major depression after a 1-week single-blind placebo period. Thirty-five patients completed at least 3 weeks of active medication, while 25 patients completed all 6 weeks. Response rates, whether defined by end-of-treatment Hamilton Rating Scale for Depression (HAM-D) score less than 10 or by a 50% reduction in HAM-D scores, were equivalent for the two medications. For fluoxetine, HAM-D scores were significantly lower at Weeks 1 and 2 compared with those of trazodone. Trazodone improved sleep significantly more than fluoxetine. Fluoxetine was associated more frequently with weight loss (p = .002) and less frequently with dizziness (p = .04) than trazodone. The safety and efficacy of nortriptyline and fluoxetine were compared in a double-blind, randomized, multicenter 5-week trial involving 205 outpatients with acute major depression of moderate severity. Seventy-two nortriptyline and 84 fluoxetine patients completed at least 2 weeks of medication and were included in the efficacy analysis; all patients were evaluated for side effects. Average total scores on the Hamilton Rating Scale for Depression (HAM-D) for both treatment groups declined from 22-23 at baseline to 11.5 at the conclusion of the 5-week period. At Week, 5, 71% of nortriptyline patients and 65% of fluoxetine patients were much or very much improved. Fluoxetine was associated more frequently with nausea (p less than .05), while nortriptyline was associated more frequently with dry mouth (p less than .05). These results are discussed in the context of selecting between nortriptyline and fluoxetine for a particular depressed patient. The efficacy of fluoxetine was evaluated in depressed patients in double-blind imipramine- and placebo-controlled clinical trials. Fluoxetine produced greater improvement than placebo on all major efficacy parameters and was comparable to imipramine with respect to the primary indicators of depression. Fluoxetine had significantly less associated anticholinergic effects, dizziness, drowsiness, somatosensory disturbance, and excessive sweating than imipramine. Although nausea occurred more frequently in fluoxetine patients, it was generally mild and well tolerated. A significantly smaller percentage of fluoxetine than imipramine patients terminated therapy because of adverse experiences. One hundred and eighty three patients with DSM-III-R major depressive illness were allocated randomly 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 claims of specific adverse effects of fluoxetine on anxiety and suicidality. The efficacy and safety of fluoxetine were compared with those of imipramine and of placebo in a 6-week randomized double-blind parallel study of patients with major depressive illness. Mean values for all efficacy measurements were improved over baseline with fluoxetine and imipramine treatment (p less than .001). More fluoxetine patients completed the study than did imipramine or placebo patients. Predominant adverse experiences reported by imipramine patients were dry mouth and dizziness/lightheadedness. Predominant adverse experiences reported by fluoxetine patients were drowsiness/sedation and excessive sweating. In a subsequent 48-week open-label study, the predominant adverse experience in the fluoxetine group was excessive sweating and in the imipramine group was still dry mouth. In this study, fluoxetine relieved the symptoms of major depressive illness effectively and significantly better than placebo and was better tolerated than imipramine. This was a 6-week, double-blind comparison of fluoxetine, imipramine, and placebo in 89 patients with bipolar depression. Using the criteria of greater than or equal to 50% improvement in the HAMD-total score after at least 3 weeks on study drug, endpoint analysis showed 86% of the fluoxetine-treated patients improved compared with 57% of the imipramine-treated and 38% of the placebo-treated patients. Significantly fewer fluoxetine-treated patients discontinued due to adverse events than did imipramine-treated patients (7% vs. 30%, respectively). The clinical efficacy and safety of fluoxetine and imipramine were compared in a double-blind, 5-week, parallel study in 40 depressed outpatients. Mean scores for most depression scales improved more in patients taking fluoxetine than in those receiving imipramine (p less than .05). Nine of 16 (56%) fluoxetine patients who completed the study and 1 of 19 (5%) imipramine patients were not at all depressed at the end of the study (p less than .001). Seven fluoxetine patients and 14 imipramine patients reported one or more adverse effects during treatment; no fluoxetine patient terminated the study early for drug-related reasons. It was concluded that fluoxetine provides effective antidepressant activity with fewer and less troublesome side effects than imipramine. A double-blind clinical trial was undertaken to evaluate the clinical efficacy and safety of fluoxetine compared with imipramine in the treatment of 59 outpatients suffering from major depressive disorder. The mean scores of all depression rating scales showed that the drugs had comparable efficacy. The side effect profile of imipramine was found to be mainly anticholinergic, which was not the case for fluoxetine, where it was mainly found to be gastrointestinal, such as nausea and diarrhoea. In both groups the total number of adverse events reported were the same. Fluoxetine treatment resulted in weight loss, whereas imipramine treatment resulted in a slight but significant weight increase. nan Depression is treated by a great variety of antidepressant treatments. SSRIs (such as fluoxetine) are well known: it is, however, sure that further progress is needed and the search for antidepressants with other mechanisms of action (such as tianeptine) or different efficacy is still of interest.
                A multinational study compared tianeptine with fluoxetine in 387 patients with Depressive Episode, or Recurrent Depressive Disorder, or Bipolar Affective Disorder (ICD-10), in a double-blind parallel group design. They were treated for six weeks.
                At inclusion, no significant difference between groups was shown. Final MADRS scores were 15.7 and 15.8 with tianeptine and fluoxetine, respectively (ITT population) (p = 0.944). MADRS responders were 58% and 56% with tianeptine and fluoxetine, respectively (p = 0.710). No statistical difference was observed for the other efficacy parameters. Thirty-six withdrawals occurred in each group, without any difference for the reasons of discontinuation. There was no major difference between groups for the other safety parameters.
                In this study, both tianeptine and fluoxetine exhibited a good efficacy and safety. Depression has emerged as a contrastive area of gender differences in psychiatry, as epidemiological data has consistently shown depression is twice as common in women as men. The pharmacodynamic effect of antidepressants may also show gender differences, as suggested by reports of better response of young women to non-tricyclic antidepressants.
                The antidepressive effect of an SSRI (fluoxetine) and a tetracyclic antidepressant with selective norepinephrine reuptake inhibitory effect (maprotiline) was compared in a 6-week, double-blind trial of 105 depressed patients.
                No significant difference was observed in the change of HAMD17 total score from baseline to week 6 between fluoxetine- and maprotiline-treated patients. A significant difference was observed in females (fluoxetine, -17.8; maprotiline, -13.9; P=0.017) between treatment groups, but not in males. Amongst females, the difference was significant in women aged <44 years (fluoxetine, -18.4; maprotiline, -12.9; P=0.023) but not > or =44 years.
                Females in their reproductive period are more responsive to SSRI (fluoxetine) than norepinephrinergic tetracyclic antidepressant (maprotiline) treatment. Normal cyclical ovulation, and estrogen release may have a clinically relevant pharmacodynamic interaction with serotonergic antidepressants. 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 outpatients. 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. In a double-blind study in a primary-care setting in France, outpatients fulfilling DSM IV criteria for a major depressive episode were randomised to receive sertraline (50 to 150 mg/day; n = 122) or fluoxetine (20 to 60 mg/day; n = 120). Assessments, including clinical evaluation [Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI)] and quality of life [Functional Status Questionnaire (FSQ)], were made at study entry and after 4 and 6 months of treatment. Use of medical services, absences from work and productivity losses were recorded for calculation of direct and indirect costs from both the overall societal perspective and in terms of sickness insurance. In total, 231 patients (116 receiving sertraline, 115 receiving fluoxetine) were included in an intention-to-treat analysis assessed up to the last visit. Statistically significant clinical and quality-of-life improvements from baseline were observed in both treatment groups, with no between-group differences. Utilisation of medical resources was higher in fluoxetine-treated patients, with significantly more consultations with specialists. The 2 treatment groups were similar in terms of number of hospitalisations and duration of stay, whether related to depression or not. There were no significant differences between groups for work or productivity losses. Cost comparisons favoured sertraline treatment from both the societal (FF7780 vs FF8706) and sickness insurance (FF2936 vs FF3224) viewpoints, with cost differentials of FF926 and FF288, respectively. From the societal perspective, the total cost per patient over the 6-month course of the trial, irrespective of the study treatment given, was FF8241, and the corresponding sickness insurance cost was FF3079. At the time of the study, FF1 = $US0.1993. The efficacy and tolerability of the selective reversible monoamine oxidase A inhibitor, moclobemide (300 mg/day) and the selective serotonin uptake inhibitor, fluoxetine (200 mg/day), were compared in a six-week single-centre double-blind fixed-dose study in patients (n = 42) with double depression (DSM-III-R: dysthymia with superimposed major depressive episode) using weekly assessment on the Hamilton depression rating scale (HDRS-17 items) and clinical global impression (CGI) scale. The primary efficacy outcome measure was a decrease > or = 50% in end of treatment HDRS score, secondary measures were the mean total endpoint HDRS scores and percentages of CGI very good and good responses. Tolerability was measured by the frequency and severity of volunteered adverse events. There were no significant differences in secondary efficacy outcome measures, but more patients achieved a > or = 50% decrease in HDRS score on moclobemide (71% vs 38%, p < 0.05). The only adverse event was mild transient anxiety (n = 1) with moclobemide. The results suggest that moclobemide and fluoxetine are equally well tolerated and at least similar in efficacy in double depression. Evidence that moclobemide may be more effective requires confirmation in a larger comparative study incorporating a placebo control group. The response of patients with major depressive illness to fluoxetine or dothiepin was compared in a double-blind multi-centre trial. No differences in efficacy were observed, but the profile of side-effects differed with tremor, rash, nausea and headache occurring with fluoxetine, and drowsiness, dizziness and visual disturbance with dothiepin. It is likely that fluoxetine will be marketed with a proposed dose range lower than the one used here. Fluoxetine and imipramine were compared in a six-week, double-blind, randomized trial in 118 men and women, ages 18 to 70 years, hospitalized for major depressive disorder. Treatment groups were comparable at baseline. Median maintenance doses were: fluoxetine, 80 mg/day; imipramine, 200 mg/day. Efficacy with fluoxetine and imipramine was comparable: none of the between-treatment differences was statistically significant. Mean +/- standard deviation baseline HAMD21 total scores and change (last-visit-carried-forward analysis), respectively, were fluoxetine, 28.0 +/- 5.3 and -8.5 +/- 9.9; imipramine, 27.0 +/- 5.8 and -11.9 +/- 9.0. Response and remission rates, respectively, were fluoxetine, 54.5 and 21.2%; imipramine, 60.0 and 34.3%. Discontinuations for adverse events were comparable (fluoxetine, 21.4%; imipramine, 22.6%). Common treatment-emergent events with fluoxetine were dry mouth (28.6%), constipation (17.9%), and somnolence (17.9%); those with imipramine were dry mouth (58.1%), constipation (32.3%), and headache (22.6%). Fluoxetine was as effective as imipramine in this population of inpatients. To compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Chinese patients suffering moderate-to-severe depression.
                133 patients with a diagnosis of major depressive episode (DSM-IV) and scoring 15 or more on the 17-item Hamilton Rating Scale for Depression (HAM-D) were randomly assigned to receive 6 weeks of treatment with either mirtazapine (15-45 mg/day) or fluoxetine (20-40 mg/day). Efficacy was assessed using the HAM-D and Clinical Global Impressions scale, with analyses performed on the intent-to-treat sample using the last-observation-carried-forward method. Safety analysis was based on the all-subjects-treated group.
                Mean daily doses were 34.1 mg for mirtazapine (N = 66) and 30.7 mg for fluoxetine (N = 66). Thirty patients in the mirtazapine group and 22 in the fluoxetine group dropped out. Both drugs proved equally effective for reduction of the overall symptoms of depression throughout the treatment period. At day 42, the mean reductions in HAM-D total score (compared with baseline) were 11.8 and 10.6 for the mirtazapine and fluoxetine groups, respectively; however, the changes were not statistically significant. Both treatments were well tolerated, with more nausea and influenza-like symptoms observed for the fluoxetine group, and greater weight increase and somnolence for the mirtazapine analog.
                Both mirtazapine and fluoxetine were indistinguishable in effectiveness for treatment of depressive symptoms, and both were well tolerated by our population of depressed Chinese patients. In line with analogous Western reports, the safety of mirtazapine and fluoxetine was comparable for our depressed Chinese patients; however, slightly different side effect profiles were noted for the 2 drugs in our study. The efficacy and safety of fluoxetine and desipramine were compared in a 6-week double-blind, parallel group study of patients with major depression. Twenty-five were studied while hospitalized for treatment, and 33 were studied as outpatients. Improvement on the Hamilton Rating Scale for Depression was significant for both treatments from week 1 through the end of the study and did not differ between the two treatments at any week. Overall, 64% of fluoxetine-treated patients and 68% of desipramine-treated patients had at least a 50% reduction in Hamilton Depression score. We assessed whether improvement relatively early in treatment was predictive of categorical response at 6 weeks. Among fluoxetine-treated patients, but not desipramine-treated patients, the week 3 change in the Hamilton Depression mood item was significantly predictive of the response at 6 weeks. Patients treated with fluoxetine had significantly fewer side effects than those treated with desipramine. Desipramine, but not fluoxetine, caused a persistent increase in heart rate. The results suggest that early signs of response to fluoxetine are not dependent on achieving steady-state levels of the drug. nan Fluoxetine, a selective serotonin reuptake inhibitor, was compared to amineptine, a tricyclic antidepressant agent, in the treatment of 63 outpatients with major depressive disorders of mild or moderate severity. Patients were randomly 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. A study was conducted to compare the relative efficacy of fluoxetine and phenelzine in patients with mood-reactive atypical depression. Forty-two patients with atypical depression by the Columbia criteria were studied in a randomized, double-blind treatment study. Following a single-blind placebo lead-in, patients received fluoxetine 20-60 mg/day or phenelzine 45-90 mg/day for 6 weeks. Efficacy was measured by the Hamilton Depression Rating Scale, the Clinical Global Impression (Severity and Improvement) scales, and the Patient Global Impression (Improvement) scale. Of 42 patients randomized, 2 patients never received drugs and 2 phenelzine-treated patients dropped out prior to completion; the remainder completed the 6 weeks of the study. The rates of treatment response did not differ between groups. With a few exceptions (e.g., tremor), phenelzine produced more frequent adverse effects than fluoxetine. It was concluded that fluoxetine is as effective as phenelzine in the treatment of atypical depression, but produces fewer adverse effects and is better tolerated. This randomized, double-blind, parallel-group design study of 100 outpatients with major depressive disorder is the first study in the United States to compare the efficacy and tolerability of fluvoxamine (100-150 mg/day) and fluoxetine (20-80 mg/day). After a variable, single-blind, washout period, patients were randomized to receive either fluvoxamine (51 patients) of fluoxetine (49 patients) for 7 weeks. Efficacy was assessed with the 21-item Hamilton Rating Scale for Depression (HAM-D), and Clinical Global Impressions scale for severity and improvement. Eighty-four percent of each treatment group completed the study with each group having a mean score at end point of less than 10. Both groups demonstrated a 60% improvement in HAM-D scores over the 7-week trial. There were no statistically significant differences observed between the two groups on any efficacy parameter. The medications were well tolerated, with only two patients in each group who were terminated because of side effects. There were differences in the side-effect profiles, with fluvoxamine being associated with less nausea than fluoxetine. In summary, fluvoxamine and fluoxetine were equally effective in reducing depressive symptoms, but the two drugs displayed slightly different side-effect profiles. It has been suggested that serotonin reuptake inhibitors (SSRIs) may be less effective than tricyclic antidepressants (TCAs) in treatment of melancholic depression. We treated 36 depressed ambulatory patients with doxepin or fluoxetine in a double-blind, randomized 6-week trial with placebo run-in. Seven patients treated with doxepin and 13 patients treated with fluoxetine met diagnostic criteria for melancholic depression. Average daily dose was 169.4 +/- 41.6 mg for doxepin and 36.8 +/- 18 mg for fluoxetine. We observed a 50% response rate in both treatment groups, using as outcome criterion reduction of Hamilton Depression Scale Score to less than 10. Regardless of how strict the definition of response, we found fluoxetine to be as effective as doxepin in our group of melancholic outpatients. A large proportion of the elderly population complains of depressive symptoms. The ideal antidepressant for these patients, who often suffer from numerous concomitant diseases, should not worsen their cognitive functions and should be free of contraindications.
                To assess the effects of 2 selective serotonin reuptake inhibitors on cognitive functions in elderly depressed patients (ICD-10 criteria), we conducted a double-blind, randomized, parallel-group, multicenter study comparing paroxetine (20-40 mg daily) and fluoxetine (20-60 mg daily) treatment for 1 year. Cognitive performance was evaluated by means of the Buschke Selective Reminding Test, the Blessed Information and Memory Test, the Clifton Assessment Schedule, the Cancellation Task Test, and the Wechsler Paired Word Test; the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Anxiety Scale were administered to assess the course of depressive and anxiety symptoms, respectively.
                242 patients were enrolled (mean +/- SD age = 75.4 +/- 6.6 years). During the study, no deterioration of cognition was observed; on the contrary, most of the tested cognitive functions improved. Good antidepressant efficacy was maintained for over 1 year with both drugs, based on the percentage of responders to treatment (patients achieving a HAM-D total score < 10; 60%). Both drugs showed a good tolerability and safety profile.
                The 2 antidepressants proved to be suitable for the long-term treatment of depression in the elderly and to be devoid of detrimental effects on the tested cognitive functions. Duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, was evaluated for therapeutic efficacy and safety/tolerability in the treatment of major depression.
                In an 8-week multicenter, double-blind, placebo-controlled study, 173 patients (aged 18-65 years) with DSM-IV major depressive disorder were randomly allocated to receive placebo (N = 70), duloxetine (N = 70), or fluoxetine, 20 mg q.d. (N = 33). Duloxetine dose was titrated in the first 3 weeks in a forced-titration regimen from 40 mg (20 mg b.i.d.) to 120 mg/day (60 mg b.i.d.). Patients were required to have a Clinical Global Impressions (CGI)-Severity of Illness scale score of at least moderate severity (> or = 4) and a 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score of at least 15. Patients could not have had any current primary DSM-IV Axis I diagnosis other than major depressive disorder, or any anxiety disorder as a primary diagnosis within the past year, excluding specific phobias. The primary efficacy measurement was the HAM-D-17 total score, and secondary measures included the Montgomery-Asberg Depression Rating Scale, CGI-Severity of Illness and CGI-Improvement, and Patient Global Impression of Improvement. Safety was evaluated by recording the occurrence of discontinuation rates and treatment-emergent adverse events and by measurement of vital signs and laboratory analytes.
                Duloxetine was superior to placebo in change on the HAM-D-17 (p = .009). Estimated probabilities of response and remission were 64% and 56%, respectively, for duloxetine, compared with 52% and 30% for fluoxetine and 48% and 32% for placebo. Duloxetine was numerically superior to fluoxetine on the primary and most of the secondary outcome measures. In general, duloxetine was well tolerated; 76% of patients achieved the maximum dose, and insomnia and asthenia were the only adverse events reported statistically significantly (p < .05) more frequently by duloxetine-treated patients compared with placebo-treated patients.
                These data indicate that duloxetine is efficacious for the treatment of major depressive disorder and is well tolerated and safe. This was a 6-week, double-blind, randomized trial of the efficacy and tolerability of venlafaxine and fluoxetine in 109 patients with major depression and melancholia. Hospitalized and day care patients with DSM-IV major depression and melancholia and a baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of > or = 25 were eligible. The doses were venlafaxine 75 mg/day or fluoxetine 20 mg/day from days 1-4, venlafaxine 150 mg/day or fluoxetine 40 mg/day from days 5-10, and venlafaxine 225 mg/day or fluoxetine 60 mg/day from days 11-42. The intention-to-treat analyses included 55 patients on venlafaxine and 54 on fluoxetine. At the final evaluation, 70% of patients with venlafaxine and 66% with fluoxetine had > or = 50% reduction in the MADRS score, and 70% with venlafaxine and 62% with fluoxetine had a Clinical Global Impression (CGI) score of 1 or 2. A CGI improvement score of 1 was observed in 51% of patients with venlafaxine and 32% with fluoxetine (P = 0.018). A final Hamilton Depression Rating Scale (HAM-D) score < 7 was attained in 41% of venlafaxine-treated and 36% of fluoxetine-treated patients. Overall, 22% of patients in each group discontinued therapy, but only 5% on venlafaxine and 9% on fluoxetine discontinued for adverse events. Nausea was reported in 5.5% of venlafaxine-treated patients and 14.8% of fluoxetine-treated patients. Venlafaxine was effective and well tolerated for treating inpatients with major depression and melancholia. Based on remission criteria (HAM-D < 7 or CGI of 1), venlafaxine was superior to fluoxetine. Previous small trials have suggested that nefazodone does not suppress rapid-eye-movement (REM) sleep or increase REM latency in depressed patients, in contrast to fluoxetine. The effects of nefazodone and fluoxetine on sleep architecture and on clinician- and patient-rated sleep measures were directly compared in this 8-week, multicenter, double-blind, randomized, parallel-group study.
                Forty-four outpatients with moderate to severe, nonpsychotic major depressive disorder (DSM-III-R) and insomnia were randomly assigned to receive nefazodone (Days 1-7, 200 mg/day; Days 8-56, 400 mg/day) or fluoxetine (Days 1-56, 20 mg/day). Sleep measures were obtained at baseline, while patients were unmedicated, and at Weeks 2, 4, and 8 of treatment.
                In 43 evaluable patients (23 nefazodone, 20 fluoxetine), nefazodone and fluoxetine demonstrated similar antidepressant efficacy. All significant values were p < .05. Fluoxetine significantly decreased sleep efficiency and REM sleep and increased number of awakenings, Stage 1 sleep, and REM latency compared with baseline. In contrast, nefazodone significantly decreased percentage of awake and movement time and did not alter sleep efficiency or number of awakenings, Stage 1 or REM sleep, or REM latency compared with baseline. Nefazodone was associated with significantly less change from baseline for sleep efficiency, number of awakenings, percentage of awake and movement time, percentage of REM and Stage 1 sleep, and REM latency compared with fluoxetine. Both fluoxetine- and nefazodone-treated patients also showed significant improvement in some clinician- and patient-rated sleep disturbance scores, but nefazodone-treated patients improved to a significantly greater extent than fluoxetine-treated patients in most measures.
                While nefazodone and fluoxetine showed equivalent antidepressant efficacy, more objective, subjective, and clinician-rated measures of sleep disturbance were improved during treatment with nefazodone than with fluoxetine. These results suggest that antidepressant effects of medications can occur independently of drug-induced changes in objective, subjective, and clinician-rated measures of sleep. Further studies, including parallel placebo-controlled comparisons with nefazodone, are needed to further test this hypothesis. nan To compare the efficacy and tolerability of mirtazapine and fluoxetine in depressed inpatients and outpatients.
                Patients with a major depressive episode (DSM-III-R), a baseline score of > or=21 on the 17-item Hamilton Rating Scale for Depression (HAM-D), and > or=2 on HAM-D Item 1 (depressed mood) were randomly assigned to a 6-week treatment with either mirtazapine (N=66, 15-60 mg/day) or fluoxetine (N=67, 20-40 mg/day). The upper limit of the mirtazapine dose range was above the dose range approved in the United States (15-45 mg/day). Efficacy was evaluated by the HAM-D, Clinical Global Impressions, the Visual Analogue Mood Rating Scale (VAMRS), and the Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ). The efficacy analyses were performed on the intent-to-treat group using the last-observation-carried-forward method.
                Mean total 17-item HAM-D scores at baseline were 26.0 for the mirtazapine- and 26.1 for the fluoxetine-treated group. The decrease from baseline on the HAM-D was larger in the mirtazapine than in the fluoxetine group throughout the treatment period, reaching statistical significance at days 21 and 28. At assessments from day 21 and onward, the absolute difference between the 2 study groups favoring mirtazapine ranged from 3.7 to 4.2 points, the magnitude of difference usually seen between an efficacious antidepressant drug and placebo. Mean dosages at weeks 1-4 were 36.5 mg/day for mirtazapine and 19.6 mg/day for fluoxetine; the respective dosages at weeks 5-6 were 56.3 mg and 35.8 mg. Similar numbers of patients dropped out due to adverse events; tolerability profiles were comparable except for changes in body weight from baseline which were statistically significantly more pronounced in the mirtazapine group compared to the fluoxetine group.
                We found that mirtazapine was as well tolerated as fluoxetine and significantly more effective after 3 and 4 weeks of therapy. A sample of 120 patients, all of whom met DSM-III criteria for major unipolar depressive disorder, were randomly allocated to two treatment groups. Sixty patients were treated with fluoxetine and 60 with clomipramine during a 6-week period. No significant difference was found in antidepressant efficacy, with improvement occurring on both drugs. Important differences were found in the side-effects profile of each group, their incidence being significantly lower and tending to disappear during the course of treatment in the group of patients treated with fluoxetine. 1. The effects of fluoxetine and amitriptyline on the electrocardiogram (ECG) and systolic time intervals (STIs) were measured during a double-blind parallel-group study in depressed patients. 2. ECGs and STIs were measured after a 1 week placebo run-in, following 1 week's treatment with fluoxetine 40 mg daily or amitriptyline 100 mg daily, and then after 3 weeks' treatment with fluoxetine 60-80 mg daily or amitriptyline 150-200 mg daily. 3. Fluoxetine had no effect on the ECG or STIs at any dose. Amitriptyline 150-200 mg daily shortened the sinus cycle length by a mean of 12%, prolonged the PR interval by 8% and the QRS duration by 10%. Amitriptyline did not significantly alter the STIs. We conducted a randomized, double-blind, placebo-controlled study of the efficacy and safety of once-daily venlafaxine extended release (XR) and fluoxetine in outpatients with major depression and concomitant anxiety.
                Patients who met DSM-IV criteria for major depressive disorder and satisfied eligibility criteria were randomly assigned to once-daily venlafaxine XR, fluoxetine, or placebo for 12 weeks. Efficacy was assessed with the Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions scale.
                Among 359 outpatients, venlafaxine XR and fluoxetine were significantly superior (p < .05) to placebo on the HAM-D total score beginning at week 2 and continuing to the end of the study. Venlafaxine XR but not fluoxetine was significantly better than placebo at week 2 on the HAM-D depressed mood item. At week 12, the HAM-D response rate was 43% on placebo, 67% on venlafaxine XR, and 62% on fluoxetine (p < .05). The HAM-D remission rate was significantly higher (p < .05) at weeks 3, 4, 6, 8, 12, and final evaluation with venlafaxine XR and at weeks 8, 12, and final evaluation with fluoxetine than with placebo. The HAM-A response rate was significantly higher (p < .05) with venlafaxine XR than with fluoxetine at week 12. The incidence of discontinuation for adverse events was 5% with placebo, 10% with venlafaxine XR, and 7% with fluoxetine.
                Once-daily venlafaxine XR is effective and well tolerated for the treatment of major depression and concomitant anxiety and provides evidence for superiority over fluoxetine. In a 6-week, multicentre, randomised, double-blind controlled study, tianeptine (37.5 mg/day) and fluoxetine (20 mg/day) were compared for efficacy and safety in 178 patients with major depression. No significant difference was shown between the two drugs, either in terms of efficacy (MADRS, CGI, COVI) or in terms of safety, except for the CGI 'severity of illness' which was lower at the end point with tianeptine than with fluoxetine. The percentages of responders (as defined by a 50% decrease of the MADRS score from baseline to end point) were 75% with tianeptine and 67% with fluoxetine, showing the efficacy of both drugs. In conclusion, both tianeptine and fluoxetine are effective and well-tolerated treatments for major depression.
                Copyright 2002 John Wiley & Sons, Ltd. Depression in the elderly appears to be frequently poorly understood and underdiagnosed. The frequency of depressed illness in subjects over the age of 65 years is an important problem of health care. General practitioners are often in the first line of care. The objective of this trial was to compare the efficacy and safety of fluoxetine 20 mg/day to tianeptine 37.5 mg/day in elderly patients suffering from major depressive episode defined according to DSM III-R criteria, Newcastle Depression Scale < or = -20, without associated dementia Mini Mental Status (MMSE), treated by general practitioners in ten different french regions during 3 months. 237 patients were randomised, each patient had to be treated for 12 weeks and was reviewed 5 times during the trial. Patients had signed an informed consent. This trial was in favor of the superiority of fluoxetine compared to tianeptine. The main criterium, defined as the difference of the Montgomery and Asberg Depression Rating scale (MADRS) score between day 0 and day 84, was significantly different in favour of the fluoxetine group (intent to treat and per protocol analysis) (p = 0.019). The success rate at the end of the treatment (MADRS < or = 10) was significantly higher in the fluoxetine group (fluoxetine group: 48.4% vs tianeptine group: 28.1%) (p = 0.005). These results were confirmed by analysis of the other assessment criteria Geriatric Depression Scale (GDS) and Clinical Global Impression (CGI). During the study, the safety of the two treatments was comparable. This double-blind, randomised, multicentre study compared the antidepressant efficacy and safety of two doses of milnacipran (100 mg/day and 200 mg/day) and fluoxetine (20 mg/day) in 289 inpatients with endogenous depression. After a placebo washout period of 4-7 days, assessments were performed weekly during the first 4 weeks, and then after 6, 8 and 12 weeks, using the 17-item Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression (CGI). HDRS total score was reduced by a mean of 14.8 in the milnacipran 100 mg/day group, 12.9 in the milnacipran 200 mg/day group and 12.1 in the fluoxetine 20 mg/day group. MADRS total score decreased by 17.4, 15.8 and 14.6, respectively. No significant difference could be shown between the three treatment groups for either the HDRS or MADRS total scores. However, the time-by-time change showed a trend in favour of milnacipran 100 mg/day, which was found significantly superior to fluoxetine at day 28 for several converging parameters (MADRS, CGI-3). Overall, efficacy ratings for all parameters were highest for milnacipran 100 mg/day, followed by milnacipran 200 mg/day and fluoxetine 20 mg/day. Side-effect profiles were not significantly different between groups except for a significantly greater frequency of dose-related increase in heart rate > or = 100 bpm in milnacipran recipients and a significantly greater weight loss in fluoxetine recipients. Many claims 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 randomized controlled trials. The authors used a randomized study design to evaluate differential compliance with antidepressant medications in a primary care setting.
                A total of 152 patients treated in 10 primary care practices in the United Kingdom were included in a randomized, open-label, parallel-group study of fluoxetine and dothiepin at therapeutic doses for 12 weeks. Compliance was assessed by using pill count, patient questionnaires, and the Medication Event Monitoring System.
                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 Questionnaire 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.
                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. Eighteen outpatients with major depression (diagnosis was made according to DSM-III criteria) were treated in a 5-week double-blind parallel group comparison of the new antidepressant fluoxetine with imipramine. From these results it can be shown that the drugs were comparable in efficacy, although because of the small sample size a moderate clinical difference between treatments may not have been detected. Imipramine and fluoxetine have already been compared in other studies, but never at such a low dosage (20 mg) for fluoxetine. At this dosage the fluoxetine safety profile seems to be very different from previous scheduled studies with higher dosages. In fact clinical efficacy seems to remain comparable while side-effects are significantly less frequent. Depression is associated with considerable morbidity and mortality. As depressive disorders carry a high risk of relapse, treatment strategies include the use of a 6-month continuation period after resolution of the acute episode. Tolerability is of major importance when determining compliance and outcome during long-term therapy. Due to the superior tolerability profile of the selective serotonin reuptake inhibitors (SSRIs) over the older tricyclic antidepressants (TCAs), the former may be more suitable for extended therapy. Comparative studies have not shown differences between the SSRIs in terms of efficacy, but side-effect profiles may vary. A multicenter, double-blind, comparative study of sertraline and fluoxetine was carried out in outpatients fulfilling DSM-III-R criteria for major depressive disorder. Patients were randomised to receive sertraline (50-150 mg, n = 118) or fluoxetine (20-60 mg, n = 120) for 24 weeks. Assessments for depression (HAM-D, HAD, CGI-I, CGI-S), anxiety (Covi), sleep (Leeds Sleep Evaluation scale) and quality of life (SIP) were made at study entry and at weeks 2, 4, 8, 12, 18 and 24. All adverse events were recorded to allow evaluation of tolerability. In total, 88 patients in the sertraline group completed the study compared with 79 in the fluoxetine group. Side effects were responsible for the premature treatment withdrawal of seven (6%) sertraline patients and 12 (10%) fluoxetine patients. Two-hundred and thirty-four patients were included in an ITT analysis up to last visit (116 sertraline, 118 fluoxetine). At study endpoint, both treatments produced a significant improvement over baseline on all efficacy variables (P < 0.001). Although the magnitude of global changes in depression, anxiety, and quality of life was larger with sertraline than fluoxetine, none of the between-group differences reached statistical significance. However, significant differences in favour of sertraline were observed for individual HAM-D items including item 4 (insomnia onset) (P = 0.04), item 9 (agitation) (P = 0.02), and item 13 (general somatic symptoms) (P = 0.008). In addition, sertraline was associated with significantly superior performance on the Leeds Sleep Evaluation scale and on SIP items relating to sleep and rest, emotional behaviour and ambulation. Both sertraline and fluoxetine were well tolerated with no significant differences between treatments. In a randomized, controlled, double-blind trial, 70 patients (mean age, 49.7 years) suffering from mild to moderate depression received one tablet of either St. John's Wort (Hypericum perforatum) extract (Calmigen) or fluoxetine hydrochloride (Prozac) twice a day for 6 weeks. Efficacy was determined according to the 17-item Hamilton Rating Scale for Depression (HAMD), the von Zerssen depression scale (DS), Clinical Global Impression (CGI), and patients' overall evaluation. Significant decreases (P<.001) of 50% in the Hypericum group and 58% in the fluoxetine group in the HAMD score and of 42% and 52% on the DS spoke to the efficacy of both medications. The Hypericum extract achieved 83% of the efficacy of fluoxetine on the HAMD and 78% on the DS. Assessments by physicians (CGI) and patients indicated considerable improvement with no between-treatment differences. Of the 9 dropouts (13%), 2 in the Hypericum group and 2 in the fluoxetine group were due to adverse reactions. Safety evaluations demonstrated only minor changes. The Hypericum preparation tested in this study is therapeutically equivalent to fluoxetine and is therefore a rational alternative to synthetic antidepressants. 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, randomized, parallel trial, 124 subjects with Research Diagnostic Criteria-compatible agitated depression were randomized 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. We report results from a multicenter, placebo-controlled, randomized, double-blind comparison of the efficacy and tolerability of paroxetine and fluoxetine in outpatients with major depression. Across five U.S. sites, 128 outpatients (mean age: 41.3 +/- 12.6; 63 men and 65 women) with moderate to moderately severe major depression without a history of mania or hypomania were recruited between 1993 and 1994. All 128 patients completed a 1-week placebo washout period, and were then randomized to 12 weeks of double-blind treatment with paroxetine up to 50 mg/day (n = 55), fluoxetine up to 80 mg/day (n = 54), or placebo (n = 19). Subjects were evaluated weekly for the first 4 weeks, then at weeks 6, 9, and 12 with the 21-item HAMD and the Covi Anxiety Scale. There were no significant differences among the three treatment groups in baseline and endpoint depression and anxiety severity, as well as in the degree of depression and anxiety improvement. There were no statistically significant differences in rates or mean numbers of adverse events between paroxetine-treated patients and fluoxetine-treated patients. In summary, our results, although limited by the lack of a significant difference from placebo in treatment outcome, suggest that the SSRIs paroxetine and fluoxetine have comparable antidepressant and antianxiety efficacies among depressed outpatients, as well as similar safety and tolerability profiles. nan 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. The antidepressant efficacy and side effect profile of a fixed dose of 20 mg/day of fluoxetine, a specific serotonin reuptake inhibitor, were compared to those of amitriptyline. Fifty-eight patients with DSM-III-R depression were randomly assigned to receive either fluoxetine or amitriptyline. Fifty-six patients (fluoxetine N = 23, amitriptyline N = 23) completed the 6 week study. Comparable antidepressant efficacy was demonstrated for the two drugs. Patients taking fluoxetine reported less side-effects than those taking amitriptyline. nan We compared the efficacy and tolerability of venlafaxine XR with that of fluoxetine in a multicenter, randomized, double-blind, placebo-controlled study in depressed outpatients.
                Outpatients, 18 years and older, who met DSM-IV criteria for major depressive disorder were included (n = 301 randomized; 232 completed). Patients were randomly assigned to eight weeks of treatment with either venlafaxine XR 75-225 mg/day (n = 100), fluoxetine 20-60 mg/day (n = 103), or placebo (n = 98). The primary efficacy outcome measures were the final ratings on the Hamilton Rating Scale for Depression (HAM-D21) total score, HAM-D21 depressed mood item, Montgomery-Asberg Depression Rating Scale total score, and Clinical Global Impressions Scale.
                Withdrawal from the study due to adverse events occurred in 6% of the patients in the venlafaxine XR group and 9% of the patients in the fluoxetine group. Patients treated with venlafaxine XR, but only rarely those treated with fluoxetine, had statistically significant improvements in their depression ratings compared with placebo at the end of the study. The percentages of patients who achieved full remission of their depression (HAM-D21 total score < or = 7) at the end of treatment were 37%, 22% and 18% for the venlafaxine XR, fluoxetine and placebo groups, respectively. The differences in remission rates between venlafaxine XR and the other groups were statistically significant (p < 0.05).
                The superior remission outcome observed with venlafaxine XR treatment needs to be replicated in additional studies.
                Venlafaxine XR is a well-tolerated and efficacious treatment for depression. The results of this study suggest that venlafaxine XR is as well-tolerated as fluoxetine but may have some efficacy advantages over fluoxetine. A double-blind clinical trial was undertaken to evaluate clinical efficacy and safety of fluoxetine in comparison with the standard tricyclic antidepressant, imipramine, in the treatment of depressive illness. The opportunity was taken to compare the relationship of some standard 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 questionnaire (Pilowsky et al., 1969). The aim of this study was to compare the efficacy and tolerability of reboxetine, a uniquely selective noradrenaline reuptake inhibitor, with the selective serotonin reuptake inhibitor, fluoxetine. A double-blind, randomized, parallel-group, multicentre design was employed. One hundred and sixty-eight patients with acute major depressive episodes were randomized to receive oral reboxetine (8-10 mg/day) or oral fluoxetine (20-40 mg/day). The treatment period was 8 weeks. Reboxetine and fluoxetine were similarly effective as assessed by the mean reduction in total Hamilton Depression Rating Scale score, the percentage of responders and patients in remission, Clinical Global Impression severity of illness and global improvement scores and Montgomery-Asberg Depression Rating Scale. A sub-analysis of patients with severe depression indicated that reboxetine had superior efficacy compared with fluoxetine. Both treatments resulted in some improvement in Social Adaptation Self-evaluation Scale total scores and this was more evident for those patients treated with reboxetine who achieved remission. Both treatments were well tolerated. The results indicate that reboxetine is an effective and well tolerated antidepressant, being more effective than fluoxetine in patients with severe depression, and more effective in terms of social functioning in those patients who achieved remission. The efficacy and tolerability of moclobemide (300-600 mg daily) and fluoxetine (20-40 mg daily) were compared in a 6-week, double-blind study of 65 inpatients and 34 outpatients suffering from major depressive episodes (DSM III-R). No statistically significant differences between the two treatment groups were noted regarding efficacy (HDRS, CGI) or safety (adverse events, laboratory examination, vital signs). Moclobemide (300-600 mg daily) and fluoxetine (20-40 mg daily) would thus appear to be comparable both in antidepressant efficacy and tolerability. Doubling the low dosage in non-responders after 3 weeks resulted in a statistically significant improvement of CGI in the moclobemide group by comparison with the fluoxetine group at study end, suggesting that 600 mg moclobemide/day can still improve the patient's condition, while 40 mg fluoxetine/day does not. Sexual dysfunction was reported in two patients taking fluoxetine. Few studies have compared the treatment efficacy of the 2 selective serotonin reuptake inhibitors sertraline and fluoxetine.
                A randomized, single-blind, parallel-group study of 10 weeks' duration comparing the efficacy of sertraline, 50 mg/day; sertraline, 100 mg/day; and fluoxetine, 20 mg/day, was conducted in 44 psychiatric outpatients with DSM-IV unipolar major depressive disorder. Antidepressant dosages were doubled at 6 weeks for subjects who had not achieved remission. Primary outcome measurements included the 21-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions-Improvement scale (CGI-I), with scores of < or = 7 on the HAM-D and < or = 2 on the CGI-I representing a positive treatment response, i.e., remission.
                At 4 weeks, significant differences in rate of positive treatment response were noted, with 0% for sertraline, 50 mg; 46% for sertraline, 100 mg; and 31% for fluoxetine, 20 mg (p = .023). At 6 weeks, positive treatment response rates were 21%, 43%, and 31% for subjects taking 50 mg of sertraline, those taking 100 mg of sertraline, and those taking 20 mg of fluoxetine, respectively, with treatment groups no longer differing significantly from each other. In subjects for whom antidepressant dose was doubled at week 6, response rates at week 10 (4 weeks on increased dose) were 40% for sertraline, 100 mg; 43% for sertraline, 200 mg; and 55% for fluoxetine, 40 mg.
                Subjects taking sertraline, 100 mg, and fluoxetine, 20 mg, demonstrated an earlier treatment response compared with subjects taking sertraline, 50 mg. For patients without a positive response at 6 weeks, an increased antidepressant dose resulted in remission for a substantial proportion of patients when assessed 4 weeks later. The efficacy and tolerability of moclobemide (300 or 600 mg daily) and fluoxetine (20 or 40 mg daily) were compared in a 6-week, double-blind study of 25 inpatients and 24 outpatients who had major depressive episodes without psychotic features (DSM-III-R). Although the clinical results of this study suggest better efficacy with moclobemide and better tolerability with fluoxetine, a statistically significant difference between treatment groups was noted only with respect to Clinical Global Impressions recorded after 10 days of therapy; these were significantly better in the moclobemide group. A daily dosage of 300 mg of moclobemide and 20 mg of fluoxetine would thus appear to be comparable both in antidepressant efficacy and tolerability. In a randomised double-blind comparative trial, the antidepressant efficacy of a daily dose of 800 mg of the St. John's wort extract LoHyp-57 (dry extract of St. John's wort, drug extrakt ratio 5-7:1, solvent, ethanol 60% [w/w]) was shown to be equivalent to that of 20 mg fluoxetine (CAS 54910-89-3) in elderly patients with mild or moderate depressive episodes according to ICD 10 (International Statistical Classification of Diseases and Related Health Problems). Treatment was given for six weeks. 149 out-patients (129 females and 20 males) were included in the intention-to-treat analysis. 72 of these patients were assigned to the ICD 10 diagnostic criterion F32.0 (mild depressive episode), while 77 patients were suffering from moderate depressive episodes, corresponding to F32.1. The principal target criterion was the patient's global score on the HAMILTON Depression Scale (items 1-17). During the six-week course of treatment with LoHyp-57, the HAMILTON global score fell from 16.60 points at entry to 7.91 points, and in the fluoxetine sample it fell from 17.18 to 8.11 points. In the group of patients with mild depressive episodes, the score showed a mean fall from 14.21 to 6.21 points on LoHyp-57, and from 15.21 to 7.46 points on fluoxetine. In patients with moderate depressive episodes, the score showed a mean fall from 18.73 to 9.43 points on LoHyp-57 and from 19.10 to 8.75 points on fluoxetine. The efficacy of both medications was found to be equivalent both in mild and moderate depressive episodes. Both treatment groups showed adverse drug reactions (ADRs). Twelve ADRs with a possible relationship to the study medication were reported during treatment with LoHyp-57. Six patients were prematurely withdrawn from treatment with the study medication for this reason. On fluoxetine 17 ADRs occurred with a possible relationship to the study medication. These led to abandonment of treatment and therefore premature withdrawal from the study in 8 cases. Fluoxetine (20 mg) was compared to dothiepin (150 mg) in a multicentre, prospective, double blind, randomised clinical trial involving 125 patients with major depression treated for an initial phase of 6 weeks and then followed up for a further 6 months. There was no difference in the efficacy of the two drugs based on the results of established rating scales (MADRS, HAM-D, BPRS). The impact of both drugs on sleep measured using the Leeds Sleep Evaluation Questionnaire showed no significant differences between treatments, however drowsiness and disturbed sleep were reported more frequently as side effects with dothiepin. Symptoms of anxiety responded equally well to both treatments. The short term and long term tolerability of dothiepin was inferior to that of fluoxetine. The place of dothiepin in treatment should be reassessed in the light of its anticholinergic adverse event profile, particularly in the elderly. Copyright 2000 John Wiley & Sons, Ltd. This was an 8-week, multicenter, randomized, double-blind, parallel-group study of the efficacy and tolerability of venlafaxine and fluoxetine.
                Outpatients with DSM-III-R major depression, a minimum score of 20 on the 21-item Hamilton Rating Scale for Depression (HAM-D), and depressive symptoms for at least 1 month were eligible. Patients were randomly assigned to treatment with venlafaxine, 37.5 mg twice daily, or fluoxetine, 20 mg once daily. The dose could be increased to venlafaxine, 75 mg twice daily, or fluoxetine, 20 mg twice daily, after 3 weeks for a poor response. The primary efficacy variables were the final on-therapy scores on the HAM-D, Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impressions Severity of Illness (CGI-S) and Improvement (CGI-I) scales.
                Three hundred eighty-two patients were randomly assigned to therapy and included in the intent-to-treat analysis. Both venlafaxine and fluoxetine produced significant reductions from baseline to day 56 in mean HAM-D, MADRS, and CGI-S scores, but no significant differences were noted between groups. Among patients who increased their dose at 3 weeks, significantly (p < .05) more patients taking venlafaxine than taking fluoxetine had a CGI-I score of 1 (very much improved) at the final evaluation. The most frequent adverse events were nausea, headache, and dizziness with venlafaxine and nausea, headache, and insomnia with fluoxetine.
                These results support the efficacy and tolerability of venlafaxine in comparison with fluoxetine for treating outpatients with major depression. Twenty-eight elderly inpatients suffering from major depressive episodes (diagnosed according to DSM III) received randomly, on a double-blind basis, amitriptyline (75 mg/die) or fluoxetine (20 mg/die) for five weeks. There were four drop-outs in the amitriptyline group and two drop-outs in the fluoxetine group. Both groups showed a significant amelioration at the end point for Hamilton Rating Scale of Depression scores compared to the baseline value. Anticholinergic side-effects were significantly more severe in the amitriptyline group. Weight gain was detected only in patients receiving amitriptyline. A total of 27 subjects began active treatment in this double-blind study comparing the efficacy and safety of trazodone and fluoxetine in geriatric depressed patients, but only 13 completed 6 weeks on study medication. Both agents were effective according to weekly and endpoint analyses, and there was no evidence of significant effects on blood pressure, pulse, or weight. Separate analysis of patients who had received an adequate trial of medication indicated a trend toward relatively more fluoxetine-treated patients meeting clinical criteria for resolved depression. The efficacy of moclobemide (300-450 mg/day) was compared with fluoxetine (20-40 mg/day) in a double-blind, multicentre study in 209 patients with new episodes of depression selected from 612 consecutive depressed patients representative of those consulting psychiatric services in Finland. Antidepressant efficacy was assessed with the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale and Clinical Global Impression (CGI). The Medical Outcome Study Short-form General Health Survey (SF-20) and 15D Measure of Quality of Life were used to measure effectiveness in terms of health-related quality of life. Efficacy was evident with both drug treatments, with 67% in the moclobemide group and 57% in the fluoxetine group having a reduction in HDRS of more than 50%. Similarly, 77% of the patients in the moclobemide group and 67% in the fluoxetine group were assessed on the CGI as much better or very much better after 6 weeks of treatment. The most commonly reported adverse events were nausea, other gastrointestinal symptoms, nervousness, dizziness and sleep disorders. Nausea was significantly more common in the fluoxetine group and was found especially in women. Premature terminations of treatment were 18% in the moclobemide and 21% in the fluoxetine group. A significant change for the better in quality of life was found in both treatment groups, even at week 2 but especially after 6 weeks of treatment. Improvement was not only seen in dimensions measuring depression or mental health but also in other dimensions. Fluoxetine, a new serotonin uptake blocking antidepressant, was compared with amitriptyline in a double-blind study. Patients were diagnosed as having major depression, according to DSM-III criteria, when interviewed with the Diagnostic Interview Schedule. There was significant improvement in patient and observer ratings of depression in both groups, with no difference between groups. Recent memory improved significantly in the fluoxetine group but not in the amitriptyline group. Numbers of patients reporting side-effects were similar but the profiles of side-effects were different, with more patients on amitriptyline reporting anticholinergic and intolerable side-effects. This study was undertaken to compare the efficacy and safety of bupropion and fluoxetine.
                Moderately to severely depressed outpatients who fulfilled the DSM-III-R criteria for nonpsychotic major depressive disorder and had a score of 20 or more on the Hamilton Rating Scale for Depression (21 item) participated in this two-center study. Following a 1-week placebo phase, patients were randomly assigned to receive either bupropion or fluoxetine for 6 weeks of double-blind treatment. Weekly efficacy assessments included Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. Vital signs and adverse experiences were also assessed weekly.
                A total of 61 patients were randomly assigned to receive bupropion (225-450 mg/day) and 62 were randomly assigned to receive fluoxetine (20-80 mg/day). The mean daily dose at the end of the study was 382 mg/day for the bupropion treatment group and 38 mg/day for the fluoxetine treatment group. There were no statistically significant differences between treatments on any of the efficacy variables. On the basis of a 50% or greater reduction in the HAM-D scores, 63% (N = 37) of the bupropion-treated and 58% (N = 35) of the fluoxetine-treated patients were categorized as responders, and on the basis of CGI scores, 68% (N = 40) of the bupropion-treated and 58% (N = 35) of the fluoxetine-treated patients were rated as much or very much improved. HAM-A scores decreased by 59% for both treatment groups. The incidence of treatment-emergent adverse events was low with no statistically significant differences between treatments. Twenty-six percent (N = 16) of the bupropion-treated and 29% (N = 18) of the fluoxetine-treated patients prematurely discontinued treatment.
                Both bupropion and fluoxetine demonstrated similar efficacy in relieving depression and accompanying symptoms of anxiety, and both exhibited a similar, favorable safety profile. Sleep disturbances are common in major depressive disorder. In previous open-label trials, nefazodone improved sleep continuity and increased rapid eye movement (REM) sleep, while not affecting stage 3/4 sleep or REM latency: in contrast, fluoxetine suppressed REM sleep. This study compared the objective and subjective effects of nefazodone and fluoxetine on sleep.
                This paper reports combined results of three identical, multisite, randomized, double-blind, 8-week, acute-phase trials comparing nefazodone (n = 64) with fluoxetine (n = 61) in outpatients with nonpsychotic major depressive disorder and insomnia. Sleep electroencephalographic (EEG) recordings were gathered at baseline and weeks 2, 4, and 8. Clinical ratings were obtained at weeks 1-4, 6, and 8.
                Nefazodone and fluoxetine were equally effective in reducing depressive symptoms; however, nefazodone differentially and progressively increased (while fluoxetine reduced) sleep efficiency and reduced (while fluoxetine increased) the number of awakenings in a linear fashion over the 8-week trial. Fluoxetine, but not nefazodone, prolonged REM latency and suppressed REM sleep. Nefazodone significantly increased total REM sleep time. Clinical evaluations of sleep quality were significantly improved with nefazodone compared with fluoxetine.
                Nefazodone and fluoxetine were equally effective antidepressants. Nefazodone was associated with normal objective, and clinician- and patient-rated assessments of sleep when compared with fluoxetine. These differential sleep EEG effects are consistent with the notion that nefazodone and fluoxetine may have somewhat different modes and spectra of action. In this randomized, open-label, 8-week comparative study, the efficacy and safety of venlafaxine and fluoxetine were assessed in outpatients with major depression. One hundred forty-five patients were assigned to receive venlafaxine 37.5 mg twice daily or fluoxetine 20 mg once daily. On day 15, if clinically indicated to improve patient response, the dosage could be increased at the investigator's discretion to venlafaxine 75 mg twice daily or fluoxetine 40 mg once daily. One hundred forty-five patients were evaluated for safety and 110, for efficacy. The mean age was 37 years, and 70% of the patients were female. In both treatment groups, mean scores on the Hamilton Depression Rating Scale decreased significantly between baseline (27.8, venlafaxine; 29.2, fluoxetine) and the end of the study (8.7, venlafaxine; 8.2, fluoxetine). Similarly, mean scores on the Montgomery-Asberg Depression Rating Scale decreased significantly between baseline (31.4, venlafaxine; 31.6, fluoxetine) and the end of the study (8.3, venlafaxine; 7.6, fluoxetine). In venlafaxine patients, the most common adverse events were nausea (44.3%), headache (40.0%), insomnia (31.4%), dizziness (30.0%), and dry mouth (22.9%); in fluoxetine patients, they were headache (32.0%), nausea (28.0%), insomnia (24.0%), anxiety (21.3%), sleepiness (20.0%), and generalized tremor (20.0%). The results of this study indicate that venlafaxine is effective and well tolerated for the treatment of major depression at doses of 37.5 or 75 mg twice daily and not significantly different from fluoxetine 20 or 40 mg once daily. A double-blind, multinational study was conducted to compare the efficacy and safety of fluvoxamine and fluoxetine in outpatients with major depressive episode; 184 patients were randomised to fluvoxamine (100 mg/day) or fluoxetine (20 mg/day) for 6 weeks. Both drugs were effective and there were no statistically significant differences between them in the area under the curve of change from baseline in the Hamilton depression rating scale (HAMD) total score. However, the percentage of HAMD responders (>or= 50% decrease in HAMD total score) at week 2, the clinical global improvement severity of illness score at week 2 and the depression subscale of the irritability, depression and anxiety scale at weeks 1, 2 and 4, all showed significant advantages for fluvoxamine. During the last 2 weeks, fluvoxamine was significantly more effective in improving the HAMD sleep disturbance scale. Both drugs were well tolerated and there were no marked differences in their side effect profiles which were typical of SSRIs. Fluvoxamine and fluoxetine have similar efficacy and safety profiles in the treatment of major depressive episode; the findings of this study indicate that fluvoxamine may have a faster onset of action with respect to resolution of depressive symptoms and result in a better improvement in sleep quality.
                Copyright 2003 John Wiley & Sons, Ltd. Moclobemide and fluoxetine were tested in a six-week trial involving 122 patients with major depressive illness. Patients initially received moclobemide, 150 mg three times daily, or fluoxetine 20 mg/day, but during weeks 3, 4, 5 and 6 the doses could be altered, giving a range of 300-600 mg/day for moclobemide or 20-40 mg/day for fluoxetine. No dietary restrictions were imposed on the patients. The trial was completed by 49 patients receiving moclobemide, and 43 patients receiving fluoxetine. The efficacies of these two agents, as determined on the Hamilton Depression Rating Scale and from Clinical Global Assessments, were found not to differ significantly. The frequencies of occurrence of adverse reactions were also similar, but sedation, nausea and vomiting were reported more frequently with fluoxetine, and insomnia was experienced with moclobemide. Tolerance of both drugs was judged to be high. Accumulating evidence suggests that noradrenergic and serotonergic drugs are equally effective in ameliorating the depressive symptoms of major depression. Major depression is associated also with memory impairments, but the comparative effects of the antidepressant drugs on memory are not clear. We previously found that serotonergic neurotransmission is of particular importance for some aspects of episodic memory. We set out to test whether treatment with the selective serotonergic drug Fluoxetine (Prozac) would be advantageous in this respect over treatment with the selective noradrenergic tricyclic antidepressant drug Desipramine (Deprexan). Seventeen patients with major depressive episode, randomly assigned for treatment with either Fluoxetine (n = 8) or Desipramine (n = 9), were assessed for their clinical situation and for memory performance at the beginning of treatment, after 3 weeks, and after 6 weeks of pharmacological treatment. We found that although clinically both drugs were equally effective, the improvement of memory performance in the Fluoxetine-treated patients was significantly greater compared with that of the Desipramine-treated patients. The results support the role of serotonin in memory. More studies in larger samples of patients are required, but it may be that in cases where memory impairment is a major symptom, it would be beneficial to consider serotonergic antidepressant drugs for treatment. Furthermore, in cases where, for various reasons, the treatment of choice is noradrenergic, it may be worthwhile to consider a supplementary serotonergic drug to improve memory deficits. 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. Fluoxetine, a selective inhibitor of 5-HT uptake, was compared to dothiepin in a double-blind study of 6 weeks duration in 100 depressed patients (male and female) drawn from 8 general practices. Only those who scored at least 17 on the first 17 questions of the Hamilton Psychiatric Rating Scale for Depression (HAM-D) were selected. Both groups improved throughout the trial, though the dothiepin treated patients tended to improve quicker. However, by the end of the trial there was no statistically significant difference between the 2 groups. Subset analyses of HAM-D scores associated with anxiety and sleep revealed no statistically significant differences between the 2 treatments though improvement in anxiety scores was marginally greater for those receiving fluoxetine by the end of the trial. Other global assessments by patients and doctors confirmed the changes in HAM-D scores. Statistically significant weight changes occurred between visits 1 and 5. Whereas fluoxetine-treated patients lost weight (p less than 0.05), dothiepin-treated patients gained weight (p = 0.05) over this period. Adverse effects were reported in 27 patients given fluoxetine and 20 dothiepin. Of these, 14 fluoxetine and 7 dothiepin-treated patients withdrew before the end of the trial. The most common adverse effects were nausea, vomiting and diarrhoea in the fluoxetine group and tiredness, drowsiness and diarrhoea in the dothiepin group. There were no haematological or clinical chemistry changes. This study assessed whether fluoxetine, sertraline, and paroxetine differ in efficacy and tolerability in depressed patients and the impact of baseline insomnia on outcomes. Patients (N = 284) with DSM-IV major depressive disorder were randomly assigned in a double-blind fashion to fluoxetine, paroxetine, or sertraline for 10 to 16 weeks of treatment. Using the Hamilton Rating Scale for Depression (HAM-D) sleep disturbance factor score, patients were categorized into low (<4) or high (>or=4) baseline insomnia subgroups. Changes in depression and insomnia were assessed. Safety assessments included treatment-emergent adverse events (AEs), reasons for discontinuation, and AEs leading to discontinuation. In addition, AEs were evaluated within insomnia subgroups to determine emergence of activation or sedation. Depression improvement, assessed with the HAM-D-17 total score, was similar among treatments in all patients (p = 0.365) and the high (p = 0.853) and low insomnia (p = 0.415) subgroups. Insomnia improvement, assessed with the HAM-D sleep disturbance factor score, was similar among treatments in all patients (p = 0.868) and in the high (p = 0.852) and low insomnia (p = 0.982) subgroups. Analyses revealed no significant differences between treatments in the percentages of patients with substantial worsening, any worsening, worsening at endpoint, or improvement at endpoint in the HAM-D sleep disturbance factor in either insomnia subgroup. Treatments were well tolerated in most patients. No significant differences between treatments in the incidence of AEs suggestive of activation or sedation were seen in the insomnia subgroups. These data show no significant differences in acute treatment efficacy and tolerability across fluoxetine, sertraline, and paroxetine in major depressive disorder patients. Improvement in overall depression and in associated insomnia was achieved by most patients regardless of baseline insomnia. 1. This was a randomized, double-blind comparison of the efficacy and safety of venlafaxine and fluoxetine in outpatients with major depression. 2. Three hundred fourteen patients were randomly assigned to either venlafaxine 37.5 mg twice daily or fluoxetine 20 mg once daily for a maximum of 8 weeks. 3. If the response was inadequate after two weeks of treatment, the dosage of venlafaxine could be increased to 75 mg twice daily. 4. A clinical response, defined as at least a 50% decrease from baseline in the total HAM-D score, was attained at week 6 in 72% of patients on venlafaxine and 60% of patients on fluoxetine (p = 0.023). 5. Among patients who increased their dose at 2 weeks, venlafaxine was significantly (p < 0.05) superior from week 3 onward on the HAM-D. 6. Venlafaxine 75 mg daily is comparable to fluoxetine, but at 150 mg daily, it may be superior to fluoxetine in outpatients with major depression who do not respond early to treatment. A double blind controlled trial was carried out in 65 depressed out-patients to compare the efficacy and tolerance of mianserin with fluoxetine. The two compounds present very different pharmacological activities. Mianserin is an antagonist of the alpha 2-adrenergic receptors, while fluoxetine is an inhibitor of recapture specific to serotonin. Requirements for inclusion were: depressive episode of less than 2 months duration, meeting the criteria for one of the sub-types of depression described in DSM III, with a minimum score of 25 on the Montgomery Asberg Depressive Rating Scale (MADRS). The patient's ages ranged from 18 to 65. The only psychotropic medication allowed in association to the treatment was prazepam (up to 40 mg/day). Patients gave their written consent to the study. Assessment, using the Montgomery Asberg Depression Rating Scale (MADRS), the HARD diagram, the check list for somatic symptoms and side-effects was carried out before treatment and at the end of weeks 2, 4, 8. Assessment of anxiety using the Hamilton Anxiety Rating Scale (HARS) and of sleep disturbances using a sleep questionnaire was carried out before treatment and at week 4. The 8 items of the sleep questionnaire covers the complaints listed in criteria for insomnia disorders (307.42 DSM III-R). Clinical Global Impression (CGI), Therapeutic Index (TI), Tolerance Global Impression were assessed at end-point. The 2 groups were strictly comparable in respect to the clinical status at base line (diagnosis, history and duration of the depressive illness, MADRS and HARD diagram scores).(ABSTRACT TRUNCATED AT 250 WORDS) 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 outpatients 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. A randomized, double-blind, parallel-group, 6-week study was undertaken to compare the efficacy and tolerability of once or twice daily administration of the selective serotonin reuptake inhibitors paroxetine and fluoxetine. After a 1-week placebo wash-out, patients suffering from DSM-III major depression and with a score of 18 or more on the 21-item Hamilton Rating Scale for Depression (HRSD) received either paroxetine or fluoxetine. The patients were assessed for efficacy using the HRSD, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression; for tolerability, adverse events were elicited by the use of a non-leading question and a side effects checklist. The groups of patients were comparable on entry to the study. One hundred patients were recruited into the study, of whom 78 were evaluable for the efficacy analysis. Paroxetine and fluoxetine showed comparable efficacy at the end of the 6-week treatment period, but a statistically significant difference in the number of responders at week 3 in favour of paroxetine was observed. This could suggest an earlier onset of action with paroxetine. Also, associated anxiety symptoms were significantly reduced on paroxetine compared with fluoxetine at week 3. Patients on paroxetine reported fewer adverse events than those on fluoxetine. The most commonly reported adverse events were nausea and vomiting in both groups. Pramipexole, a dopamine D2 receptor agonist, was tested in 174 patients with major depression, with or without melancholia and without psychotic features. Three daily dose levels (0.375 mg, 1.0 mg, and 5.0 mg) were compared to fluoxetine (Prozac) at 20 mg and placebo in a randomized, double-blind, parallel-group study. After a 1 week placebo run-in period, patients were treated for 8 weeks, had a post-study follow-up (week 9), and were evaluated primarily with the Hamilton Psychiatric Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinician's Global Impressions-Severity of Illness scale (CGI-SI). All patients who received one dose of study medication were included in the observed-case analysis (no missing data were replaced). Results indicated that by endpoint (week 8), patients receiving pramipexole at the 1.0 mg per day dose had significant improvement over baseline compared to the placebo group by measure of the HAM-D, MADRS, and CGI-SI. Significant improvement in this dose group was seen at other timepoints as well. The most obvious improvement was seen in the pramipexole 5.0 mg group, although a substantial dropout rate for this group precluded statistical tests vs. placebo late in the study. Patients taking fluoxetine also showed significant improvements at endpoint on the MADRS and earlier in the study on the HAM-D. No new or unusual safety concerns were generated during this study. Pramipexole helped safely alleviate the symptoms of depression at 1.0 mg per day and especially in those patients who could tolerate the escalation to 5 mg per day. Seventy inpatients with a DSM-III-R major depression were included in a double-blind, randomized, 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. An eight-week double-blind, multicentre study was performed to evaluate the efficacy and safety of sertraline vs. fluoxetine in the treatment of major depression (DSM-III-R). There were 108 out-patients, from nine Italian centres, entered into the study, of whom 88 were evaluable (48 sertraline, 40 fluoxetine). The final mean daily dose of sertraline was 72 mg and for fluoxetine it was 28 mg. Both treatment groups showed a statistically significant improvement from baseline at one week, and this was maintained until the end of treatment for all of the following measures: Hamilton Rating Scales for Depression and Anxiety, the Montgomery Asberg Depression Rating Scale, Clinical Global Impressions Scale, Zung Self-Rating Scale for Anxiety and the Leeds Sleep Evaluation Questionnaire. Although there was a numerical advantage for sertraline on several efficacy measures, there was no statistically significant difference found between the treatment groups. The incidence of adverse events was similar for both treatments; 40.4% for sertraline and 39.3% for fluoxetine. However, adverse events were generally rated by patients as of lower severity in the sertraline group. In addition, for the fluoxetine group, there was a higher incidence of agitation, anxiety and insomnia than for sertraline. Sertraline was considered to be better tolerated than fluoxetine overall, since only 9.6% of sertraline-treated patients discontinued treatment due to therapy failure whereas in the fluoxetine-treated group this figure was 19.6%. By contrast, 13.5% of sertraline-treated patients discontinued prematurely because of clinical improvement, compared with 10.7% of fluoxetine-treated patients. 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.
                Patients (N = 108) with DSM-IV major depression and high levels of anxiety (a HAM-D-Anxiety/Somatization Factor score > or =7) were randomized to fluoxetine, sertraline, or paroxetine treatment in a double-blind fashion. Changes in overall depression and anxiety were assessed.
                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.
                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. In a multicentre, double blind, parallel group study 281 patients with DSM III-R diagnosis of dysthymia or a single episode of major depression in partial remission were randomised to 3 months of treatment with amisulpride 50 mg/day or fluoxetine 20 mg/day. The baseline Montgomery and Asberg Depression Rating Scale (MADRS) total score was reduced by at least 50% in 74.1% of patients (103/139) with amisulpride and 67.4% (87/129) with fluoxetine (P =0.230). No significant differences between treatment groups were found in the reductions in mean total score with the MADRS, Widlöcher psychomotor retardation scale, Sheehan disability scale, and CGI. Anxiety measured by HAM-A total mean score decreased significantly more with amisulpride (63%) than with fluoxetine (54%; P = 0.021). There were 13 dropouts due to adverse events with amisulpride and ten with fluoxetine. The number of patients reporting at least one adverse event was similar in the two groups (amisulpride 47.5%; fluoxetine 40.9%). As expected, in the amisulpride group endocrine-like adverse events in female patients were the most common, while nausea, dyspepsia, anorexia and insomnia occurred more frequently with fluoxetine. Fluoxetine, a selective serotonin uptake inhibitor (mean dose 73 mg each morning) was compared with amitriptyline (mean dose 122 mg at night) in a double-blind study of 64 depressed out-patients. Fifty patients completed the 6-week trial. The drugs did not differ with respect to psychiatrists' ratings, but amitriptyline was slightly superior with respect to patients' ratings. The amitriptyline-treated group had complaints of dry mouth and dizziness on standing; the fluoxetine-treated group of sleep disturbances, nausea, and headaches. Using data from a larger 12-week clinical trial, the authors evaluated the comparative efficacy and safety of sertraline (n=42) and fluoxetine (n=33) in patients over age 70 with a diagnosis of major depressive disorder. Similar improvement on measures of depression, including remission of depressive symptoms, was evident, although significantly more sertraline-treated patients achieved a criterion clinical response. Significantly greater improvement for the sertraline group was apparent on the Digit Symbol Substitution Test, but not on two other measures of cognitive functioning. Although there was no difference in the rate of adverse events experienced, fluoxetine-treated patients lost significantly more body weight over the 12-week trial than did sertraline-treated patients, whereas the latter group exhibited significantly more "shaking. " nan Fluoxetine was compared to doxepin in geriatric out-patients with major depressive illness. At the end of the 6-week double-blind study, the mean endpoint scores for all rating scales were significantly improved over base-line in both treatment groups. A subsequent 48-week open-label study supported the finding that both drugs are efficacious for maintenance therapy in elderly depressed patients. Fluoxetine, which lacks anticholinergic effects and is nonsedating, was well-tolerated by most patients and had fewer total side effects than doxepin. Common drug-related side effects for fluoxetine included nervousness/anxiety and nausea. Common side effects of doxepin were dry mouth, drowsiness/sedation, constipation, and dizziness/lightheadedness. The efficacy and safety of fluoxetine, a new antidepressant agent, were assessed in a double-blind, parallel, randomized study of 44 outpatients with major depressive disorder. Following a 1-week placebo period, patients were randomly 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. The temporal dimension, particularly anticipation, appears to be a very important component in the understanding of depressed patients. In a 90-day multicentre study, the efficacy and acceptability of amineptine and fluoxetine were compared in 169 patients with major depression. Comparison of the two antidepressants was based on double-blind methods, after random allocation of the treatments between two parallel groups. The two drugs did not differ over the whole course of the study, but the improvement in scores on day 4 was globally more marked in the amineptine than the fluoxetine group. Intragroup analysis showed that amineptine was significantly superior to fluoxetine on the retardation pole of the mood, anxiety, retardation, danger scale. The positive effect of amineptine on anticipation may enable the depressed patient to make plans for the future. Anticipation may be a key dimension to be more precisely explored in specific psychopharmacological protocols with antidepressants. In the present double-blind controlled study the efficacy and safety of fluoxetine 20 mg/day versus clomipramine 75 mg/day was evaluated during 5 weeks of treatment in 30 hospitalized patients. The sample was selected according to DSM III criteria for major depressive disorders with a score of at least 18 on the first 17 items of the Hamilton Rating Scale for Depression (HRSD). Therapeutic efficacy was evaluated weekly by using HRSD, Zung Self Rating Scale for Depression, Montgomery-Asberg Scale for Depression, Clinical Global Impression for severity and improvement of depressive symptoms. Safety was monitored weekly by recording body weight, blood pressure, pulse rate, temperature, physical conditions, laboratory tests, adverse experiences and concomitant medication. The results confirm the effectiveness and good tolerability of fluoxetine in the treatment of depressive disorders. Recent studies have suggested clinical differences among selective serotonin reuptake inhibitors. In a 12-week randomized, 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.
                A total of 203 patients were randomized 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.
                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.
                Differences observed between the two drugs in antianxiety effects were limited to two measures of anxiety among several others.
                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. The atypical subtype of depression appears to be both well validated 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.
                One hundred fifty-four subjects with DSM-IV major depression who met the Columbia criteria for atypical depression were randomly 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.
                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.
                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. Sertraline and fluoxetine have pharmacokinetic and pharmacologic differences, which may be of clinical relevance.
                A randomized, double-blind, parallel-group study of 6 weeks' duration comparing the efficacy and safety of sertraline (50-100 mg/day) with those of fluoxetine (20-40 mg/day) was conducted in 286 psychiatric outpatients with DSM-III-R major depression or bipolar disorder (depressed). Primary efficacy measurements consisted of the 17-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions (CGI) scale. Secondary measurements included the Hamilton Rating Scale for Anxiety (HAM-A), the Raskin Depression Scale, the Covi Anxiety Scale, and the Leeds Sleep Questionnaire. Additionally, scores for two items and five factors from the HAM-D were analyzed.
                Efficacy was based on 124 evaluable patients in each treatment group. As measured by HAM-D and CGI-Severity scores, there was a significant (p < .001) improvement from baseline to each follow-up visit in both treatment groups with no statistically significant difference between groups. There was also no significant difference in the proportion of responders in each group. CGI-Improvement responder rates were 69% for sertraline and 67% for fluoxetine. Results of secondary efficacy measurements followed the same trend, although from the second week of treatment there was a numerical advantage (not statistically significant) for sertraline over fluoxetine in improving anxiety symptoms as measured by the total HAM-A score. Headache and nausea were the most frequently reported events for both drugs. The incidence of early patient withdrawals due to treatment-emergent adverse events was 14% for sertraline and 13% for fluoxetine. The starting dosage (sertraline 50 mg/day, fluoxetine 20 mg/day) was the final dosage in 76% of patients in both treatment groups.
                Sertraline and fluoxetine were equally effective and well tolerated in patients with major depression and associated anxiety. 8 general practitioners and 7 specialists in the field of psychiatry and neurology participated in this study evaluating the results of fluoxetine treatment in outpatients with depression in respect to safety and efficacy. They were familiarized with the requisite instruments by video rater training. The study was designed as a randomised double-blind parallel study involving 139 patients, comparing the effects of a daily dosage of 20 mg fluoxetine, 40 mg fluoxetine and 50 mg clomipramine. The number of patients treated in each group was 45, 46, and 48, respectively and altogether 125 completed the four-week study (five visits). A comparison of overall efficacy ratings showed significant antidepressant efficacy in all three treatment groups. On day 14 of the study (visit 4), patients receiving 40 mg fluoxetine showed significantly (p less than 0.05) better global improvement than patients receiving clomipramine. Treatment was well tolerated by all patients. The frequency of adverse events in response to fluoxetine was lower than under clomipramine treatment. On comparing treatment by psychiatrist and general practitioner no significant differences were found regarding age, sex, number of previous episodes and duration of the recent episode and outcome. Severe depression tended to be treated by psychiatrists; general practitioners prescribed additional medication less frequently. There has been a paucity of well-designed studies comparing selective serotonin reuptake inhibitor (SSRI) medications in the treatment of depression in the elderly. This multicenter study was designed to examine the efficacy and safety of sertraline and fluoxetine in depressed elderly outpatients. A secondary objective was to examine the effects of SSRI treatment on quality of life and cognitive function.
                Two hundred thirty-six outpatients 60 years of age and older who met DSM-III-R criteria for major depressive disorder received 1 week of single-blind placebo before being randomly assigned to 12 weeks of double-blind, parallel-group treatment with flexible daily doses of either sertraline (range, 50-100 mg) or fluoxetine (range, 20-40 mg). Primary efficacy measures consisted of the 24-item Hamilton Rating Scale for Depression and Clinical Global Impressions scale ratings. Secondary outcome assessments included clinician- and patient-rated measures of depression symptoms and factors, cognitive functioning, and quality of life, as well as plasma drug concentrations, which were correlated with clinical response.
                Both drugs produced a similarly positive response on the primary efficacy measures, with 12-week responder rates of 73% for sertraline and 71% for fluoxetine. Sertraline-treated patients showed statistically greater cognitive improvement on several measures. Both drugs were safe and well tolerated.
                Data indicate that both drugs are effective antidepressants for the treatment of depressed elderly outpatients. Differences in cognitive performance effects deserve further investigation. nan Depression is an international public health problem. Impairment in social and occupational functioning, increased comorbidity with other psychiatric and medical conditions, and an increased risk of mortality are a few of its consequences. Some psychiatrists have the impression that selective serotonin re-uptake inhibitors may not work as well as tricyclic anti-depressants in severe depression and/or melancholia. On the contrary, there is a general belief that selective serotonin re-uptake inhibitors are superior to the tricyclic anti-depressants in having fewer side-effects, particularly cardiovascular effects. The objective of this double-blind study was to compare the efficacy and safety of fluoxetine and nortriptyline in patients with moderate to severe major depression.
                A total of 48 adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (DSM IV), forth edition for major depression, based on the structured clinical interview for DSM IV participated in the trial. Patients had a baseline Hamilton Rating Scale for Depression score of at least 20. In this double-blind, single-center trial, patients were randomly assigned to receive nortriptyline 150 mg/day (group 1) or fluoxetine 60 mg/day (group 2) for 6-weeks. The outcome of the two groups was assessed using Hamilton Depression Rating Scale, a side-effect checklist and a regular ECG assessment.
                The results suggest that the efficacy of nortriptyline is superior to fluoxetine in this group of major depressed patients. No significant differences were observed between dropout rates in the two groups but anti-cholinergic side-effects were significantly more frequent with nortriptyline than with fluoxetine but there was no significant difference in cardiovascular effects in particular QTc prolongation.
                The results of the current study suggest that nortriptyline was more effective than fluoxetine in the treatment of moderate to severe depression. A larger study is warranted. Two dimensions of compliance (drop-outs and adherence) were investigated in patients treated with antidepressant drugs. Efficacy, compliance and its determinants were investigated in 66 patients suffering from major depressive disorder and treated in a double-blind manner with fluoxetine 20 mg/day or amitriptyline 150 mg/day for 9 weeks. Overall effectiveness [50% decrease in the initial Hamilton Rating Scale for Depression (HAM-D)] was similar in both groups (62.8% for fluoxetine, 58.1% for amitriptyline). The dropout rate due to side effects was 35.5% for amitriptyline and 5.7% for fluoxetine. A logistic regression analysis revealed that the initial HAM-D score was not predictive for dropping out, but this outcome was instead determined by sex (increased risk for males), age (increased risk for being younger) and occurrence of severe side effects. Adherence was estimated using electronic Medication Event Monitoring System and defined as the percentage of days when the correct dose was taken out of the medication container. Of the patients studied 37% had an adherence of less than 70%. There was no relationship between adherence and efficacy and adherence was similar in patients on fluoxetine or amitriptyline. Side effects were not predictive of being adherent or not, but a higher initial HAM-D score predicted a higher adherence to the medication regimen. The demographic variables had no significant effect. The present study suggests that the link between efficacy, side effects and compliance or adherence is more complex than is generally believed and that early termination and non-adherence seem to be determined by different factors. 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 (>or=50% reduction in HAM-D) or remission (HAM-D <or=10 points) than those who received placebo (p < 0.01 for both analyses). Similar findings were recorded in a subpopulation 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 assessments (Montgomery-Asberg 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. nan The antidepressant efficacy and short-term safety of venlafaxine and fluoxetine were compared in 68 patients hospitalized with major depression and melancholia. Venlafaxine was superior in efficacy to fluoxetine; total scores for both the MADRS and the HAM-D were significantly (p < or = 0.05) lower in the venlafaxine group than in the fluoxetine group at Weeks 4 and 6. Overall tolerance was similar for the two treatments. In a six-week double-blind randomized trial, preceded by a one-week single-blind placebo treatment, the efficacy and the side-effects of fluoxetine (40-80 mg/d) (n = 30) and maprotiline (50-150 mg/d) (n = 35) were compared in hospitalized patients with DSM-III Major Depression without psychotic features. Efficacy was measured by means of the Hamilton Depression Rating Scale, the Raskin Depression Scale, the Covi Anxiety Scale, and a Clinical Global Impression. Side-effects were evaluated by an Adverse Events Scale. A statistically significant improvement was achieved in both treatment groups but success rates were modest. No differences in efficacy were found between the two groups. In addition, no statistically significant differences were found between the two groups either in frequency or in severity of adverse events. In fact, the only statistically significant difference found was in weight change: weight loss in the fluoxetine group and weight gain in the maprotiline group. Fluoxetine (60 mg), a selective inhibitor of the reuptake of 5-HT, was compared in a double-blind trial to amitriptyline (150 mg) in a sample of 34 patients fitting the Research Diagnostic Criteria for a major depressive disorder. Patients were studied after a drug washout period of 10 days and an active treatment period of 42 days. Sleep polygraphic recordings were performed before and at the end of the study. As indicated by the significant decrease in the Hamilton Depression scale and the Montgomery Asberg Depression scale, fluoxetine showed similar antidepressant effects to amitriptyline with significantly fewer adverse effects. Fluoxetine and amitriptyline decreased the amount of REM sleep, a well known effect of classical antidepressants. Fluoxetine showed some specific effects on sleep continuity (potentially dose related) as indicated by the significant increase in the number of awakenings and in stage shifts, without interfering with the therapeutic response. 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 outpatients. The duration of the study was 6 weeks, with assessments 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 h. The objective of the present study was to compare the safety and efficacy of moclobemide versus fluoxetine in adult patients with major depressive disorder. The design of the study was a multicenter, double-blind, comparative, and randomized trial. A 1- to 2-week single-blind placebo washout phase was followed by 6 weeks of double-blind treatment with moclobemide or fluoxetine. A total of 150 patients were enrolled in the study. There were 128 patients eligible to be randomized, with 66 patients receiving moclobemide and 62 patients receiving fluoxetine. At the termination of the study, patients in the moclobemide group were receiving a mean dose of 440 mg +/- 123 mg, while the mean dose in the fluoxetine group was 35 mg +/- 8 mg. No significant treatment differences were found for any of the efficacy parameters. Headache and nausea were the most frequently reported adverse events in both treatment groups. Headache and blurred vision were reported significantly more often (P < 0.05) in the fluoxetine group, whereas significantly more dry mouth was reported (P < 0.05) in the moclobemide group. These results provide supporting evidence of the comparable efficacy of moclobemide and fluoxetine and the better tolerability of moclobemide when used in the treatment of major depressive disorder. Although common in clinical settings, major depressive disorder with associated anxious symptoms ('anxious depression') has not been well studied in antidepressant clinical trials. The aim of this study was to compare the effects of fluoxetine versus amitriptyline in this group of patients. After a single-blind placebo run-in period of 2 weeks, patients were treated on a double-blind basis with fluoxetine or amitriptyline for 8 weeks. Assessment instruments included: 21-item Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, Clinical Global Impressions, Raskin Depression Scale and Covi Anxiety Scale. A total of 157 patients were randomized to either fluoxetine or amitriptyline. Fluoxetine was given at a fixed dose of 20 mg/day and amitriptyline was given in a range of 50-250 mg/day (mean of 138.1 mg/day). Fluoxetine was comparable to amitriptyline in all efficacy measures except the HAMD sleep factor. Unwanted effects were more frequent and more severe in the amitriptyline-treated patients. Fluoxetine was comparably efficacious to amitriptyline in the treatment of major depression with associated anxiety. Since fluoxetine was far better tolerated, it is a promising alternative for this frequent and disabling condition.