Fluoxetine-treated Patients Research Articles

Fluoxetine and Desipramine in Major Depressive Disorder

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.

A double-blind, placebo-controlled study of fluoxetine in patients with DSM-III-R obsessive-compulsive disorder

We have studied the effect of three fixed daily doses of fluoxetine in patients with obsessive-compulsive disorder (OCD) diagnosed according to DSM-III-R. Two hundred and fourteen patients were evaluated in an 8-week double blind, placebo-controlled study. A statistically significantly greater number of fluoxetine-treated patients achieved the prospectively defined criteria for clinical response when compared to placebo treatment. There was a statistically significant overall difference in the PGI rating of symptom change ( P = 0.045) and a marginally significant difference ( P = 0.089) in the CGI severity rating between groups. Pairwise comparison against placebo showed a marginally statistically significantly greater improvement ( P = 0.059) in Y-BOCS-Total score for patients receiving fluoxetine 60 mg daily, and a significantly higher response rate in patients receiving fluoxetine 40 mg or 60 mg daily ( P<0.05). One hundred and sixty one patients continued to a 16-week extension evaluation. There was no significant difference in the rate of reporting of any individual adverse event between placebo and fluoxetine, and the rate of discontinuation due to adverse events was low (< 6% in each study phase). This study supports the growing evidence for the safety and efficacy of fluoxetine in the treatment of OCD.

Double-blind study of adjuvant buspirone for fluoxetine-treated patients with obsessive-compulsive disorder

In a double-blind, crossover study, 13 fluoxetine-treated patients with obsessive-compulsive disorder were given adjuvant buspirone and placebo for 4 weeks each. There were no significant differences between buspirone and placebo in obsessive-compulsive, depressive, or anxiety symptoms.

Cerebrospinal fluid monoamine metabolites in fluoxetine-treated patients with major depression and in healthy volunteers

Cerebrospinal fluid (CSF) levels of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) were measured in three groups: 46 healthy volunteers; 9 medication-free patients with DSM III-R major depressive disorder, recurrent; and these same 9 patients following at least 4 weeks of fluoxetine treatment at 20 mg/day. CSF monoamine metabolite levels in medication-free patients did not differ from healthy volunteers; however, CSF 5-HIAA and MHPG decreased significantly from 95.9 ± 24.6 (all values ± SD) to 64.2 ± 26.1 pmol/ml and from 46.7 ± 14.2 to 42.6 ± 11.6 pmol/ml, respectively, following fluoxetine treatment. Fluoxetine also significantly decreased mean Hamilton Depression Rating Scale scores from 23.2 ± 6.5 to 17.4 ± 5.0 and significantly increased the CSF HVA/5-HIAA ratio.

Fluoxetine not associated with increased aggression in controlled clinical trials.

A comprehensive meta-analysis was performed to address the possible association of fluoxetine with violence or aggression. Data from the United States Investigational New Drug Clinical Trial Databases for approved and potential indications (depression, obesity, bulimia nervosa, obsessive-compulsive disorder, smoking cessation, alcoholism; n = 3992) were evaluated. Statistically significantly fewer fluoxetine-treated patients (0.15%) than placebo-treated patients (0.65%) experienced events suggestive of aggression (hostility, personality disorder, antisocial reaction). A relative risk analysis indicated that aggression events were four times more likely to occur in placebo-treated patients than in fluoxetine-treated patients. Although the possibility that some rare phenomenon was not detected cannot be excluded, this meta-analysis did not show fluoxetine to be associated with an increased risk of emergence of violent or aggressive behaviour.

Adverse events and treatment discontinuations in fluoxetine clinical trials

A re-analysis of the profile of adverse events observed in controlled clinical trials in summarized. The data confirm that the side-effects of fluoxetine therapy are different from those of the tricyclic antidepressants (TCAs), both in type and frequency. Moreover, the superior tolerability of fluoxetine compared with the TCAs is confirmed by the significantly lower rate of premature discontinuation in the fluoxetine-treated patients than in the TCA-treated patients.

Severity of depression and response to fluoxetine

Pooled data from multiple, double-blind clinical trials comparing fluoxetine with either placebo, a tricyclic antidepressant (TCA) or both in patients with major depression were analyzed to assess the efficacy of these treatments in mild, moderate and severe depression. Fluoxetine-treated patients showed statistically significantly higher rates of response and remission than placebo-treated patients within all three severity subgroups. There were no differences in response or remission rates between fluoxetine and TCAs, regardless of symptom severity. Thus, the efficacy of fluoxetine was superior to placebo and similar to TCAs in mild, moderate and severe major depression.

Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression

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.

Fluoxetine Not Associated With Increased Violence or Aggression in Controlled Clinical Trials

AbstractBecause of interest in the possible occurrence of violent 01 aggressive behavior with serotonin-enhancing drugs, three subpools of controlled clinical trial data were evaluated: fluoxetine (n = 2615) versus placebo (n = 1377) (18 trials; depression, bulimia nervosa, obesity, alcoholism, smoking cessation); fluoxetine (n = 441) versus tricyclic antidepressants (n = 445) (ten trials; depression); and fluoxetine (n = 309) versus tricyclic antidepressants (n = 308) versus placebo (n = 297) (three trials; depression, including adjustment disorder). Adverse event terms possibly involving physically assaultive acts toward another (antisocial reaction, hostility, and personality disorder, together termed the “aggression cluster”) were reviewed. Across all indications, a statistically significantly smaller proportion of fluoxetine-treated patients than placebo-treated patients experienced one or more of the events (0.15% versus 0.65%, respectively). Placebo-treated patients were four times more likely to e...

Fluoxetine: no association with suicidality in obsessive-compulsive disorder

Since (a) obsessive-compulsive disorder (OCD) may involve serotonergic neural transmission abnormalities also thought to be related to regulation of suicide and aggression, (b) comorbidity between OCD and depression is substantial, and (c) depression is a major risk factor for suicide, a comprehensive analysis of clinical trial data was undertaken to assess the potential association of fluoxetine, a serotonin uptake inhibitor, and suicidality (suicidal acts and ideation). Pooled data from clinical trials comparing fluoxetine ( n=266) and placebo ( n=89) in patients with DSM-IIIR OCD were analyzed retrospectively. No suicidal acts occurred during placebo lead-in or double-blind therapy. Mean Hamilton Depression Scale item 3 (suicide item) scores improved statistically significantly with fluoxetine compared with placebo. Worsening in suicidal ideation was statistically significantly more frequent with placebo than with fluoxetine. Emergence of substantial suicidal ideation (change in baseline item 3 score of 0 or 1 to 3 or 4) was numerically greater with placebo than with fluoxetine (3.6% vs. 1.7%; not statistically significant). The incidence of suicidality in fluoxetine-treated patients with OCD was low, compared favorably with rates in corresponding placebo-treated patients, and was well within the range of estimates in previous studies of patients with OCD. These controlled clinical trial results suggest no undue risk of suicidality in patients with OCD treated with fluoxetine.

Controlled comparison of buspirone and clomipramine in obsessive- compulsive disorder

Eighteen outpatients with obsessive-compulsive disorder were treated with either buspirone, a partial serotonin agonist, or clomipramine, a serotonin uptake inhibitor, in a double-blind, random-assignment study. Both drugs led to statistically significant and similar improvements in scores on the Yale-Brown Obsessive-Compulsive Rating Scale and other obsessive-compulsive and depression scales. This preliminary result warrants further exploration with a larger sample and other serotonergic agents.

Fluoxetine Drug-Drug Interactions

As clinical experience with fluoxetine grows, so do reports of drug interactions. The most common adverse interaction appears to be inhibition of drug metabolism. Other antidepressants are so affected, and toxicity may result if proper dosage adjustments are not made. Pharmacodynamic interactions may also occur, as evidenced by a serotonergic syndrome with concomitant administration of MAOIs and fluoxetine. Some have speculated that worsening of EPS in some fluoxetine-treated patients may be explained by alterations in serotonergic/dopaminergic balance, although a pharmacokinetic explanation may also fit some cases. Fluoxetine has been greeted with an enthusiasm that claims some advantages over other antidepressants. We should be mindful that any unique therapeutic benefits may be accompanied by a unique adverse effects profile and a special propensity for drug-drug interactions.

A Comparison of Fluoxetine Imipramine and Placebo in Patients with Bipolar Depressive Disorder

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).

A Double-blind Comparative Study of Fluoxetine and Dothiepin in the Treatment of Depression in General Practice

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.

The Safety of Fluoxetine - An Update

Fluoxetine is a new antidepressant agent which is a selective inhibitor of neuronal serotonin uptake; it has minimal affinity for muscarinic, dopaminergic, histaminic, serotonergic, or noradrenergic receptors (Starket al, 1985). This specificity of activity suggests that fluoxetine may have a side-effect profile which is different from previously available antidepressants.The safety of fluoxetine has been extensively studied: several hundred patients have received the drug continuously for more than one year - some have had therapy for 5 years or more. Previous reviews of the safety of fluoxetine (Wernicke, 1985; Zerbe, 1986) have described a smaller population of patients than is now available.This review is drawn from data pooled from comparative clinical trials, which included 4336 patients: fluoxetine - 2938, tricyclic antidepressants (TCAs) - 599, and placebo - 799 patients. The TCAs studied were amitriptyline, imipramine, and doxepin. Most patients were adults with major depressive disorder, and the most common study design was a 6-week comparative double-blind phase, followed by unblinded long-term treatment. While the core of this study is a data base of 2938 fluoxetine-treated patients, all serious adverse events reported in over 7500 fluoxetine-treated patients worldwide, as of mid-1987, have been included.