Efficacy and safety of fluoxetine in the treatment of patients with major depression after first myocardial infarction: findings from a double-blind, placebo-controlled trial. A double-blind controlled comparison of fluoxetine and lofepramine in major depressive illness. A double-blind, randomized, placebo-controlled trial of once-daily venlafaxine extended release (XR) and fluoxetine for the treatment of depression. Compliance with antidepressant medication in the treatment of major depressive disorder in primary care: a randomized comparison of fluoxetine and a tricyclic antidepressant. Analysis of the Hamilton Depression Rating Scale factors from a double-blind, placebo-controlled trial of fluoxetine in geriatric major depression. A randomized, double-blind comparison of olanzapine/fluoxetine combination, olanzapine, fluoxetine, and venlafaxine in treatment-resistant depression. 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. Double-blind controlled study on the clinical efficacy and safety of fluoxetine vs clomipramine in the treatment of major depressive disorders. Placebo-controlled treatment trial of depression in elderly physically ill patients.
Depression and hostility are significant risk factors for mortality and morbidity after myocardial infarction (MI). Much research is still needed to identify effective ways to reduce emotional distress in patients with cardiovascular disease. This double-blind, placebo-controlled study investigated the efficacy and safety of the antidepressant fluoxetine in patients with depression after their first MI.
                Fifty-four patients with major depression after MI were randomly assigned to receive a flexible-dose regimen of fluoxetine or placebo for the first 9 weeks of a double-blind, placebo-controlled trial. Patients without serious adverse effects who wished to continue participating in the study were given fluoxetine or placebo for an additional 16 weeks. To evaluate the efficacy of fluoxetine, the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Hostility Scale of the 90-item Symptom Check List (SCL-90) were used as primary measures of outcome. To evaluate the safety of fluoxetine, cardiac function was measured before and after treatment with echocardiography and electrocardiography.
                The a priori difference in antidepressive efficacy (4-point difference in HAMD-17 scores between the fluoxetine and placebo groups) was not met. However, the response rate among patients receiving fluoxetine was significantly greater than that among patients receiving placebo at week 25 (48 vs. 26%, p = .05). Among patients with mild depression (HAMD-17 score < or =21), HAMD-17 scores were significantly different (p < .05) between the fluoxetine and placebo groups at weeks 9 (by 5.4 points) and 25 (by 5.8 points). Also, hostility scores at week 25 were significantly reduced among patients receiving fluoxetine (p = .02). Analysis of electrocardiographic and echocardiographic parameters revealed no decrease in cardiac function as a result of treatment with fluoxetine. Conclusions: Although the overall difference between the fluoxetine and placebo groups was not significant, there was a trend favoring fluoxetine in this relatively small sample. The response rate in the group receiving fluoxetine was comparable with that observed in other studies of patients with cardiovascular disease. In addition, fluoxetine seemed to be particularly effective in patients with mild depression and was associated with a statistically significant reduction in hostility. The results of this study suggest that fluoxetine can be safely used to treat patients with post-MI depression beginning 3 months after the event. 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. 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. 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. Major depression during later life represents a clinical challenge. Conventional antidepressant pharmacotherapy is relatively less well tolerated in geriatric patients compared with younger patients. Despite the striking impairments associated with this disorder, clinical investigations into the relative risk-benefit ratio of various depression treatment strategies have been limited. In this multicentre, placebo-controlled, double-blind trial with fluoxetine, 671 major depressed (DSM-III-R-compatible) outpatients aged 60 years or older were evaluated. The 21-item Hamilton Depression Rating Scale (HAMD21) response (p = 0.014) and remission (p = 0.008) criteria favoured fluoxetine over placebo. Analysis of the treatment effect on change in the HAMD21 factors (anxiety/somatization, cognitive disturbance, psychomotor retardation, and sleep disturbance) revealed advantages for fluoxetine within the cognitive disturbance and psychomotor retardation factors. Overall, the rate of discontinuation for an adverse event between fluoxetine (11.6%) and placebo (8.6%) was not statistically significant. Baseline HAMD21 factor scores were not predictive of adverse events leading to premature treatment discontinuation. Fluoxetine, 20 mg/day, is a well-tolerated and effective treatment option in the management of geriatric major depression. Based on preliminary evidence of its usefulness in treatment-resistant depression (TRD), an olanzapine/fluoxetine combination (OFC) was examined in comparison with olanzapine, fluoxetine, and venlafaxine in a TRD population. In this 12-week double-blind study, 483 subjects with unipolar, nonpsychotic TRD, with historic failure on a selective serotonin reuptake inhibitor (SSRI) and prospective failure on open-label venlafaxine, were randomized to an OFC or to an olanzapine, fluoxetine, or venlafaxine monotherapy group. Venlafaxine was continued randomly in the double-blind acute phase to explore the benefits of continuation versus switching therapy. The Montgomery-Asberg Depression Rating Scale (MADRS) total change score at end point was the primary outcome measure. The OFC group had significantly greater improvement in depressive symptoms by week 1 of treatment (MADRS mean change =-7.2, baseline =29.6), in comparison to olanzapine (-4.8, P=.03), fluoxetine (-4.7, P=.03), or venlafaxine (-3.7, P=.002) groups and maintained its statistical separation from all three monotherapy groups through week 6. At end point, the OFC group was significantly different only from the olanzapine group (-14.1 vs. -7.7, P<.001). Analysis of a subgroup of subjects who had an SSRI failure in their current depressive episode (n=334) revealed statistical separation from both olanzapine and fluoxetine (but not venlafaxine) at end point: OFC (-14.6) versus olanzapine (-9.4, P<.001) versus fluoxetine (-10.7, P=.006) versus venlafaxine (-14.7, P=.98). The OFC had a safety profile comparable to its component monotherapies (i.e., olanzapine and fluoxetine), showed a rapid onset of antidepressant effect, and was effective in this TRD sample. At the study end point, OFC, fluoxetine, venlafaxine, and low-dose OFC all appeared to be similarly effective. 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. 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. To determine the response of physically ill elderly depressed patients to treatment.
                Acute geriatric medical inpatients with depression, randomly assigned to an 8-week double-blind placebo-controlled trial of fluoxetine.
                Response rate as defined by the 17-item Hamilton Depression Rating Scale.
                Eighty-two patients entered the trial; 62 patients (all those who had completed at least 3 weeks of treatment) were included in the efficacy analysis. Forty-two completed the full 8 weeks (21 in each group) with response rates of 67% in the fluoxetine group and 38% in the placebo group. No significant difference was found between the responses of the two groups (p = 0.12). There was a trend for results in the fluoxetine group to continue to improve with time. On secondary analysis those patients with serious physical illness who completed 5 or more weeks (N = 37) showed a significant improvement in mood if treated with fluoxetine (p = 0.02).
                The main benefit of antidepressants is to approximately double the chances of recovery. This trial showed the response rate of the fluoxetine treated group was increased by a factor of 1.8 over the placebo group in an 8-week period. The presence of physical illness, often severe and/or multiple, did not reduce the effectiveness of the medication, which was well tolerated overall. Those with serious physical disease responded significantly better to drug treatment; this will require further work. Psychological support was also considered to be important.
Caution is required in interpreting the results given the methodological limitations of the included trials in terms of internal and external validity. Further, the size and clinical meaningfulness of statistically significant results are uncertain. However, given the risks of untreated depression in terms of completed suicide and impacts on functioning, if a decision to use medication is agreed, then fluoxetine might be the medication of first choice given guideline recommendations. Clinicians need to keep in mind that there is evidence of an increased risk of suicide-related outcomes in those treated with antidepressant medications.