Fluvoxamine versus imipramine and placebo: a double-blind comparison in depressed patients. A comparison of fluvoxamine and fluoxetine in the treatment of major depression. A double-blind comparative study of the clinical efficacy of fluvoxamine and chlorimipramine. A double-blind, placebo-controlled trial of fluvoxamine versus imipramine in outpatients with major depression. Perspectives in clinical psychopharmacology of amitriptyline and fluvoxamine. A double-blind study in depressed inpatients. A placebo-controlled inpatient comparison of fluvoxamine maleate and imipramine in major depression. A double-blind, randomised comparison of fluvoxamine with dothiepin in the treatment of depression in elderly patients. Venlafaxine versus fluvoxamine in the treatment of delusional depression: a pilot double-blind controlled study. A double-blind placebo-controlled study of fluvoxamine and imipramine in out-patients with primary depression. Fluvoxamine versus fluoxetine in major depressive episode: a double-blind randomised comparison. Fluvoxamine maleate in the treatment of depression: a single-center, double-blind, placebo-controlled comparison with imipramine in outpatients. Efficacy and tolerability of citalopram in comparison with fluvoxamine in depressed outpatients: a double-blind, multicentre study. The LUCIFER Group. [Comparative efficacy and tolerance of fluvoxamine and amitriptyline in the treatment of moderate and severe depression in mental hospital]. Fluvoxamine as effective as clomipramine against symptoms of severe depression: results from a multicentre, double-blind study. Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial. [Multicenter study comparing efficacy and tolerance of moclobemide and fluvoxamine in hospitalized and ambulatory patients with severe depressive episodes]. A comparative study of the efficacy and safety profiles between fluvoxamine and nortriptyline in Japanese patients with major depression. Double-blind comparative multicentre study of fluvoxamine and mianserin in the treatment of major depressive episode in elderly people. Fluvoxamine and clomipramine in depressed hospitalised patients: results from a randomised, double-blind study. A double-blind comparison of fluvoxamine and paroxetine in the treatment of depressed outpatients. [Fluoxetine versus fluvoxamine for treatment of chronic pain]. Response to total sleep deprivation before and during treatment with fluvoxamine or maprotiline in patients with major depression--results of a double-blind study. Efficacy and tolerability of moclobemide compared with fluvoxamine in depressive disorder (DSM III). A French/Swiss double-blind trial. Efficacy of fluvoxamine in obsessive-compulsive disorder. A double-blind comparison with placebo. The role of neuropharmacologic selectivity in antidepressant action: fluvoxamine versus desipramine. A double-blind randomized study comparing imipramine with fluvoxamine in depressed inpatients. Fluvoxamine maleate, a serotonergic antidepressant; a comparison with chlorimipramine. A double-blind, randomized comparison of fluvoxamine with mianserin in depressive illness. Clinical trials of fluvoxamine vs chlorimipramine with single and three times daily dosing. Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine. A controlled trial of fluvoxamine in obsessive-compulsive disorder: implications for a serotonergic theory. CPT performance in major depressive disorder before and after treatment with imipramine or fluvoxamine. Fluvoxamine CR in the long-term treatment of social anxiety disorder: the 12- to 24-week extension phase of a multicentre, randomized, placebo-controlled trial. A double-blind, placebo-controlled study of the efficacy and safety of controlled-release fluvoxamine in patients with obsessive-compulsive disorder. A double-blind comparison of fluoxetine, imipramine and placebo in outpatients with major depression. A double-blind controlled comparison of fluoxetine and lofepramine in major depressive illness. Double-blind comparison of fluoxetine and nortriptyline in the treatment of moderate to severe major depression. Plasma levels of catecholamine metabolites predict the response to sulpiride or fluvoxamine in major depression. Is baseline agitation a relative contraindication for a selective serotonin reuptake inhibitor: a comparative trial of fluoxetine versus imipramine. A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. The Venlafaxine French Inpatient Study Group.
Approximately 20 million patients suffer from major depressive disorder each year, indicating a need for antidepressant agents that are synonymous with effectiveness, tolerability and patient compliance. The authors examined the effects of fluvoxamine, a selective serotonin reuptake inhibitor, in the treatment of outpatients meeting DSM-III-R criteria for major depressive disorder. A randomized, double-blind, parallel group, placebo- and imipramine-controlled single center study was conducted in 150 outpatients. Patients were randomized to receive up to 150 mg/day of fluvoxamine as a single bedtime dose, 240 mg/day of imipramine on a twice-daily (BID) schedule, or placebo for six weeks. Efficacy measurements included HAM-D, MADRS, CGI, Raskin-Covi and SCL-56 scales. The HAM-D total score indicated that both active treatment groups showed significantly (p < or = 0.05) greater therapeutic benefit than did placebo. Severely depressed patients (HAM-D > or = 30) responded better to fluvoxamine in five of six measures. Side-effects from fluvoxamine were similar to those reported for other selective serotonin reuptake inhibitors (nausea, somnolence) and were well tolerated. Imipramine was associated with anticholinergic effects such as dry mouth and dizziness. The pharmacokinetic properties of fluvoxamine which allow the drug to be administered as a single daily dose should aid in the maintenance of patient compliance, while offering significant clinical benefit in the improvement of depressive symptoms. 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. 1 We report the results of a comparative clinical trial of a new antidepressant drug fluvoxamine (a specific re-uptake inhibitor of 5-hydroxytryptamine (5-HT)) with chlorimipramine. Thirty-two patients with mixed depression received one or the other drug at the same daily dosage of 150 mg. 2 In both drug groups there was an overall clinically significant improvement for all items on the Hamilton Rating Scale for Depression (67% improvement in both groups). 3 In the chlorimipramine group there were more digestive symptoms and anticholinergic effects; the difference with the fluvoxamine group approached statistical significance. 4 No clinically important effects of either treatment were observed on heart-rate or blood pressure. The authors employed a double-blind, placebo-controlled design to investigate the effectiveness of fluvoxamine versus imipramine in 54 outpatients with moderate major depression. Fluvoxamine proved superior to placebo but not to imipramine on the Hamilton Rating Scale for Depression and the Montgomery and Asberg Depression Rating Scale. Nausea and hyperarousal were the most common side effects in the fluvoxamine-treated patients. The efficacy of fluvoxamine was compared to that of amitriptyline in a double-blind 6-week fixed-dose trial of 56 inpatients with major depressive episode. The two drugs were comparable in their antidepressant efficacy. We tested the percentage of improvement in Hamilton-D scores during the first and the second weeks of treatment as predictors of efficacy for the last week. Improvement rates during the second week significantly predicted the outcome. We also investigated whether or not some symptomatological characteristics would permit prior prediction of the outcome with amitriptyline or fluvoxamine, dividing our sample into responders and nonresponders to the two drugs. The four groups showed differences in their symptomatological profiles. Fluvoxamine, a selective serotonin reuptake inhibitor, was investigated in a 6-week double-blind study among severely ill inpatients with DSM-III major depression. All but 1 patient also fulfilled criteria for melancholia. Following a 3-day placebo wash-out patients were randomly assigned to fluvoxamine, imipramine or placebo. Sixty of 81 patients completed at least 2 weeks following wash-out and were evaluated for efficacy. Analysis of covariance (controlling for baseline scores) showed significant (p less than 0.05) differences on CGI severity and BPRS total and a similar trend (p = 0.08) on the Hamilton Depression Scale. Fluvoxamine was superior (p less than or equal to 0.02) to both placebo and imipramine on these measures. Fluvoxamine's most common adverse effects were nausea and agitation. The number of fluvoxamine patients withdrawn for side-effects was less than imipramine and not significantly different than placebo. Fluvoxamine was not associated with significant changes in vital signs, ECG or laboratory tests. The results therefore indicate that fluvoxamine is a safe and highly effective treatment for hospitalized patients with major depression. The efficacy and tolerability of the selective 5-HT reuptake inhibitor fluvoxamine were compared with the tricyclic dothiepin in 52 elderly (age greater than 64 years) hospital patients in a multi-centre double-blind randomised trial. Patients met DSM-III criteria for 'major depressive episode' and scored greater than 29 on the Montgomery Asberg Depression Rating Scale (MADRS) after a one-week placebo baseline. Active treatment was for six weeks. The dosage of both drugs was 50 mg nocte for three days, 100 mg nocte for the remainder of the first week, thereafter increasing to a maximum of 200 mg/day according to response/tolerance. MADRS scores improved by 63.5% with fluvoxamine and 60.0% with dothiepin; there were no significant differences between treatments at any assessment. Nausea, dizziness, headache, somnolence and constipation in both groups, plus dry mouth and asthenia in the dothiepin group were more frequent than single reports. Two patients in each group discontinued treatment owing to unwanted effects. There were no clinically significant changes in haematological, biochemical or cardiovascular parameters. Previous studies have reported the efficacy of selective serotonin reuptake inhibitors as monotherapy in the treatment of delusional depression. The clinical efficacy of venlafaxine, a serotonin-norepinephrine reuptake blocker, has been demonstrated in the treatment of patients with moderate-to-severe depression, but, to date, no evidence is available about its use in depressed patients with psychotic features.
                Under double-blind conditions, 28 hospitalized patients who met DSM-IV criteria for major depression, severe with psychotic features, were randomly assigned to receive fluvoxamine or venlafaxine, 300 mg/day, for 6 weeks. Severity was evaluated using the Hamilton Rating Scale for Depression (HAM-D) and the Dimensions of Delusional Experience Rating Scale (DDERS) administered at baseline and every week thereafter. Side effects were also recorded. Clinical response was defined as a reduction of the scores in the 21-item HAM-D to 8 or below and in the DDERS to 0.
                At study completion, the response rates were 78.6% (N = 11) and 58.3% (N = 7) for fluvoxamine and venlafaxine, respectively. No significant difference was found between drugs (Fisher exact test, p = .40). Analysis of covariance on HAM-D scores did not reveal a significantly different decrease of depressive symptomatology between the 2 treatment groups (p = .14). Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded. The overall safety profile of both fluvoxamine and venlafaxine was favorable.
                The results of this pilot double-blind trial show that fluvoxamine is useful in the treatment of delusional depression and suggest that venlafaxine may also be an effective compound in the treatment of this disorder. The latter finding, although promising, warrants further replication in a larger sample of patients. 1 A double-blind placebo-controlled study of fluvoxamine and imipramine was performed in a group of depressed patients. Twenty-two patients received fluvoxamine (mean dose 101 mg/day), 25 received imipramine (mean dose 127 mg/day) and 22 received placebo. 2 Apart from an increase in the SGOT and SGPT values of four imipramine patients, no statistically significant changes in haematology or urinalysis were judged to be medically relevant. Fluvoxamine exhibited fewer anticholinergic side effects than imipramine. 3 Both fluvoxamine treated patients and imipramine-treated patients exhibited a statistically significant improvement at the end of the 28-day treatment period with respect to the placebo patients, as measured using the Hamilton Rating Scale for Depression, and the Clinical Global Impression Scale. Evaluations of the results of the Beck Depression Inventory and the Profile of Mood States revealed a statistically significant improvement for imipramine patients with respect to placebo at week 4, but not for fluvoxamine patients. It is postulated on the basis of quantitative pharmaco-EEG findings, that the slight superiority of imipramine over fluvoxamine was due to underdosing of the latter. 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. The efficacy and safety of fluvoxamine maleate, a selective serotonin reuptake inhibitor, was compared with placebo and imipramine in patients with major depressive disorder. Previous literature has cited a dose range of 100 to 300 mg/day of fluvoxamine maleate for the treatment of major depression; however, this study demonstrates that a dose range of 50 to 150 mg/day is as effective as imipramine (80-240 mg/day). After a 1- to 2-week, single-blind, placebo washout phase, 150 depressed outpatients were randomized to double-blind treatment with fluvoxamine maleate (50-150 mg/day), imipramine (80-240 mg/day), or placebo for 6 weeks. Fluvoxamine produced a significant therapeutic benefit over placebo (p < or = 0.05) as assessed by the total score on the Hamilton Rating Scale for Depression; imipramine (80-240 mg/day) produced similar results. The secondary outcome variables (i.e., Clinical Global Impression severity of illness item and 56-Item Hopkins Symptom Checklist depression factor) also showed significant differences between fluvoxamine maleate and placebo during three of the four final weeks of the study. Both fluvoxamine maleate and imipramine appeared to be safe and well tolerated by the majority of patients. As expected from the pharmacology of these agents, the imipramine groups reported more anticholinergic effects (dry mouth, dizziness, and urinary retention) and electrocardiographic effects, whereas the fluvoxamine group reported more nausea, somnolence, and abnormal ejaculation. The majority of these adverse events were mild to moderate and, with the exception of dry mouth (imipramine) and abnormal ejaculation (fluvoxamine), were transient. The data clearly demonstrate the antidepressant activity and tolerability of fluvoxamine maleate (50-150 mg/day) as compared with placebo; it is also as effective as the tricyclic antidepressant imipramine (80-240 mg/day) in patients with major depressive disorder. In 16 depression clinics in hospitals and outpatient facilities in the Netherlands, a study was performed to evaluate and compare the efficacy and tolerability of citalopram and fluvoxamine and to determine the difference in the incidence of gastrointestinal side-effects. A total of 217 patients with a depressive disorder (DSM-III-R criteria) and a score of at least 16 on the Hamilton rating scale for depression were randomized to treatment. The results of this study indicate that the two drugs are equally effective. The adverse events occurring during treatment show a similar pattern between the two drugs, but citalopram is better tolerated than fluvoxamine. Citalopram induces fewer gastrointestinal adverse events compared with fluvoxamine. However, this did not affect the drop-out rates. The aim of the study was to compare the efficacy and tolerance of fluvoxamine (FL) and amitriptyline (AM) in the treatment of patients hospitalized for moderate and severe depression and to evaluate the spectrum of antidepressive activity in FL. The study was open, randomized and comparative. Sixty patients (mean age 41 +/- 2.9 years) diagnosed as having recurrent depressive disorder, a moderate or severe depressive episode (ICD-10 F33.1, F33.2) were divided into two equal groups treated with FL or AM. The efficacies of FL and AM were comparable, with AM exhibiting an earlier clinical effect and FL having a better tolerance. FL was defined as an antidepressant with the predominantly sedative effect comparable to that of AM, but being better tolerated. Although selective serotonin reuptake inhibitors (SSRIs) are better tolerated than tricyclic antidepressants, their efficacy in severe depression remains to be further elucidated.
                A double-blind, multicentre study was conducted in 86 severely depressed inpatients (>or= 25 on the 17-item Hamilton depression rating scale [HAMD] total score) to compare the efficacy and safety of fluvoxamine with that of clomipramine. Following placebo run-in, 86 patients were randomised to receive fluvoxamine or clomipramine (100-250 mg/day) for 8 weeks.
                Fluvoxamine and clomipramine both resulted in marked improvements; there were no statistically significant differences between them on the 17-item HAMD total score, the clinical global impression severity of illness or global improvement items or the Montgomery-Asberg depression rating scale, at any visit. At the end of the study, 71% in the fluvoxamine group and 69% in the clomipramine group were responders (>or= 50% decrease in 17-item HAMD total score). However, fluvoxamine was better tolerated than clomipramine. Clomipramine was associated with a higher incidence of overall and treatment-related adverse events. In addition, the percentage of patients discontinued prematurely due to adverse events was more than twice as high with clomipramine than with fluvoxamine (24% vs 11%).
                Fluvoxamine and clomipramine are equally effective in severe depression, but fluvoxamine has a better safety and tolerability profile.
                Copyright 2003 John Wiley & Sons, Ltd. Major depression is a common psychiatric disorder in the elderly population. The efficacy of tricyclic antidepressants is well established, and selective serotonin reuptake inhibitors appear to have a similar effectiveness along with advantages in terms of tolerability and safety. Given the lack of literature data regarding fluvoxamine in the treatment of depressed elderly patients, the aim of the present study was to compare its efficacy and tolerability with those of sertraline in a sample of elderly patients.
                Under double-blind conditions, 93 hospitalized patients older than 59 years, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode, were randomly assigned to receive sertraline (150 mg daily) or fluvoxamine (200 mg daily) for 7 weeks. The clinical response was defined as a reduction on the Hamilton Rating Scale for Depression score to 8 or below.
                At study completion, the response rates were 55.6% (25/45) and 71.8% (28/39) for sertraline and fluvoxamine, respectively. No significant difference in final response rates was found between the 2 treatment groups (P = 0.12). A repeated-measures analysis of variance on Hamilton Rating Scale for Depression scores revealed a significantly different decrease of depressive symptoms between the 2 treatment groups, favoring fluvoxamine (P = 0.007). The overall safety profile of sertraline and fluvoxamine was favorable with no differences between the 2 drugs.
                The results of this double-blind trial show that sertraline and fluvoxamine may be effective compounds in the treatment of elderly depression with the latter showing some advantage in terms of speed of response. These findings warrant further replication in placebo-controlled studies. In a double blind study performed in psychiatric clinics the efficacy and tolerability of the new antidepressant Moclobemide was compared. Moclobemide belongs to a new class of substances called RIMA (Reversible Inhibitor of the monoamine oxidase type A). 61 patients with major depression (according to DSM-III) were either treated with Moclobemide or Fluvoxamine, a selective reuptake-inhibitor of 5-HT. The latter belongs to a class of antidepressants known for their better tolerability compared to tricyclic antidepressants. Moclobemide was as effective as Fluvoxamine but much better tolerated as shown by a lower incidence of side effects such as gastrointestinal problems or headache. The aim of this study was to compare the efficacy and safety profiles between fluvoxamine and nortriptyline in Japanese patients with major depression.
                The efficacy and safety profiles of fluvoxamine, a selective serotonin-reuptake inhibitor, and nortriptyline were compared under a single-blind fashion in 74 Japanese patients with major depression. The efficacy was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impression Scale (CGI) severity and improvement scores, while the safety profiles were assessed using the UKU Side Effect Rating Scale at baseline, and on days 7, 14, 28 and 56. Moreover, with the aim of determining the distinct efficacy profiles of each drug, the effects on each of the factor scores extracted by the principal component analysis performed for HAM-D scores were compared between drugs.
                Both drug groups showed significant amelioration of depressive symptomatology over the trial period lasting for 8 weeks. Statistical analyses revealed no significant between-group differences regarding the efficacy assessed by either HAM-D or CGI scores; however, the efficacy of nortriptyline tended to appear earlier than that of fluvoxamine. Moreover, no significant differences were obtained for the factor scores, representing 'depressed mood', 'physical symptoms' or 'sleep disturbances', although 'sleep disturbances' appeared to improve earlier in the nortriptyline group than in the fluvoxamine group. As for the safety profiles, the nortriptyline group scored a significantly higher incidence of adverse events such as dysarthria or orthostatic dizziness, as well as increased heart rate.
                These findings suggest that fluvoxamine is generally comparable to nortriptyline in its efficacy and superior in its safety profile, in accordance with findings obtained in previous comparative clinical trials conducted in Caucasian populations. This is a multicentre double-blind study of fluvoxamine versus mianserin in the treatment of major depressive episode in patients over 65 years of age. Fifty-seven patients received either fluvoxamine (100-200 mg daily) or mianserin (40-80 mg daily). There was no statistically significant difference in improvement between the 2 treatment groups as measured by the Montgomery-Asberg Depression Rating Scale. Eleven patients (7 in the fluvoxamine group and 4 in the mianserin group) discontinued treatment because of intolerance. No statistically significant differences were seen in biological parameters with either drug. Both drugs improved the symptoms of depression though the overall response rate was not outstanding. The side effects profile for the fluvoxamine was contrary to previous studies in that frequent nausea and vomiting were not seen. The efficacy of the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants is well established, although data on the efficacy of SSRIs in severe depression is limited. Several studies have demonstrated that fluvoxamine is as effective as clomipramine in the treatment of severe depression. The aim of this four-week study was to compare the efficacy and tolerability of fluvoxamine and clomipramine in hospitalised depressed patients. Patients were eligible for entry into the study if they had an established diagnosis of depression, and an overall score of more than 17 on the first 17-items of the Hamilton Rating Scale for Depression (HAMD). Twenty patients received fluvoxamine 100-300 mg in divided daily doses (mean daily dose 204 mg), and 20 received clomipramine 50-150 mg in divided daily doses (mean daily dose 106 mg) for four weeks. Efficacy was assessed using the HAMD and Clinical Global Impression (CGI) scales, at baseline and weekly intervals thereafter. The investigator's overall rating of efficacy and tolerability was also noted. At the end of the study, both fluvoxamine and clomipramine produced a marked to moderate therapeutic effect. Compared with baseline both fluvoxamine and clomipramine produced similar improvements in the HAMD total, HAMD item and CGI scores. More patients in the clomipramine group experienced anticholinergic side-effects and orthostatic hypotension. Furthermore, a significant difference in favour of fluvoxamine was found with regard to the investigator's overall assessment of undesirable signs and symptoms (p = 0.023; Wilcoxon's test). In conclusion, fluvoxamine is as effective as clomipramine in hospitalised depressed patients, and is better tolerated. Fluvoxamine and paroxetine, both serotonin selective reuptake inhibitors (SSRIs), were compared at two centers in a 7-week double-blind study in outpatients with major depression, diagnosed by DSM-III-R criteria.
                Sixty patients were randomly assigned to receive dosage titrated upward to between 50-150 mg/day of fluvoxamine (N = 30) or 20-50 mg/day of paroxetine (N = 30). The mean +/- SD daily dose administered at the last assessment was 102 +/- 44 mg/day for fluvoxamine and 36 +/- 13 mg/day for paroxetine. Sixteen (53%) fluvoxamine-treated patients and 10 (33%) paroxetine-treated patients were titrated to the maximum permissible dosage of either drug. Sample size was calculated to provide at least 85% power at 5% level of significance to detect at least a 1.00-point difference in mean severity of adverse events, assuming a standard deviation of 1.0.
                Fluvoxamine and paroxetine were similarly effective in ameliorating depression as demonstrated by mean total scores of 10.9 +/- 7.3 (p < .00) and 11.5 +/- 7.4 (p < .00), respectively, in the Hamilton Rating Scale for Depression (HAM-D). Adverse events were mostly mild to moderate in severity. The most common events were headache (N = 17, 57%), nausea (N = 14, 47%), sweating (N = 10, 33%), somnolence (N = 9, 30%), diarrhea (N = 9, 30%), dry mouth (N = 8, 27%), dizziness (N = 8, 27%), and, among males, impotence (N = 3, 21%) and ejaculatory abnormality (N = 3, 21%) in the paroxetine group, and headache (N = 12, 40%), somnolence (N = 12, 40%), nausea (N = 11, 37%), dry mouth (N = 11, 37%), insomnia (N = 9, 30%), asthenia (N = 7, 23%), and dyspepsia (N = 7, 23%) in the fluvoxamine group. The only statistically significant difference between treatment groups was for sweating (33% paroxetine vs. 10% fluvoxamine, p = .028).
                Observed differences in some side effects, although not statistically significant, indicate that when a patient has difficulty tolerating one SSRI, the clinician may choose to change to a different agent within the same class. This study aimed: 1) to compare the analgesic efficacy and profile of two antidepressants with the same mechanism of action (SSRI: selective serotonine reuptake inhibitors): fluoxetine vs fluvoxamine; 2) to investigate the relationship between analgesic efficacy and antidepressant effects in both drugs; 3) to evaluate the relationship between the analgesic profile and the quality (global or neuropathic) of pain.
                Fifty-three depressed patients were randomly treated with 20 mg/die of fluoxetine and 100 mg/die of fluvoxamine for chronic pain. Forty subjects (20 with fluoxetine and 20 with fluvoxamine) completed the 2-month study and were followed up on day 14, 28 and 56 of treatment. The intensity and quality of pain was assessed using Quid and depression-anxiety symptoms with the Hamilton Rating Scale (HAMD).
                The intensity and overall quality of pain deteriorated at day 14 in the fluvoxamine group and improved in those treated with fluoxetine. However, a comparable level of analgesia was achieved with both drugs at 2 months. After 2 weeks the neuropathic component of pain improved in patients treated with fluvoxamine. The improvement in pain observed in patients treated with fluoxetine depended on an improvement in depressive symptoms, whereas this relationship was not observed in the fluvoxamine group.
                Although a comparable level of analgesia was observed after two months of treatment, the two drugs show different analgesic profiles. Their analgesic action appears to depend on different mechanisms. To test the hypothesis that the antidepressant effects of total sleep deprivation (TSD) are linked to the serotonergic and/or noradrenergic system the authors carried out a double-blind study (fluvoxamine versus maprotiline) in 42 inpatients with endogenous depression (ICD). Patients were randomized to a four-week treatment with either fluvoxamine (100-300 mg/day) or maprotiline (100-300 mg/day). In addition, patients underwent a TSD procedure before and after one week of antidepressant medication. There was a statistically significant reduction of depression ratings (HDRS) in both the fluvoxamine and maprotiline group. The day-1 response to TSD before antidepressive medication was not associated with a clear relationship to the outcome after four weeks of treatment with either fluvoxamine or maprotiline. On the other hand, the day-2 response to TSD was significantly correlated with a good outcome to subchronic treatment with maprotiline. Furthermore, the results of the authors' data suggest that a favorable short-term outcome of TSD may be connected to antidepressants enhancing the serotonergic neurotransmission. The global comparison between fluvoxamine and maprotiline revealed that the group of patients treated with fluvoxamine had a significantly higher efficiency index (CGI) than the maprotiline group; fluvoxamine was rated to be tolerated excellently in 70% of the patients whereas this percentage was only 43% in the maprotiline group. There was also significantly more vertigo and dry mouth in the maprotiline group whereas the fluvoxamine group was rated to have significantly more sleep disturbances during the trial. The efficacy and tolerability of moclobemide and fluvoxamine, two new types of antidepressant agents, were compared in a multicentre, double-blind prospective study of patients with a diagnosis of major depressive episode (DSM III). Patients were randomized to receive either moclobemide (150 mg) or fluvoxamine (50 mg) twice daily for 7 days, immediately following a washout period of at least 1 week. Dosages were increased where necessary on day 8, to a maximum of moclobemide 450 mg or fluvoxamine 200 mg and in most cases were maintained at these levels for the remainder of the study period (4-6 weeks). Both treatment groups showed a marked antidepressant effect. While both treatments were well tolerated, moclobemide showed a more favourable side-effect profile than fluvoxamine. Of the 126 patients eligible for evaluation, 34 withdrew from therapy, 22% in the moclobemide group and 30% in the fluvoxamine group. Adverse events were reported in 41.8% of patients treated with moclobemide compared to 60.3% of patients in the fluvoxamine group. Reports of dry mouth and other anticholinergic effects were more frequent among those treated with fluvoxamine. A greater number of gastrointestinal complaints, especially nausea, also occurred in the fluvoxamine-treated patients. A six- to eight-week double-blind placebo-controlled trial of the potent and selective serotonin reuptake inhibitor fluvoxamine was conducted in 42 patients with primary obsessive-compulsive disorder (OCD). Approximately one half of the patients also had symptoms of major depression. Fluvoxamine was significantly better than placebo on all measures of obsessive-compulsive symptoms. Nine of 21 patients were responders ("much improved") with fluvoxamine compared with no responders with placebo, and fluvoxamine was effective in patients with OCD both with and without secondary depression. Response of OCD was not correlated with severity of baseline depression. These data lend partial support to the serotonin hypothesis of OCD. However, since a number of patients failed to respond to fluvoxamine, the role of other neurochemical systems in this disorder needs to be explored. Forty patients with a diagnosis of major depressive disorder were entered in a double-blind study to assess comparative clinical response and pharmacologic parameters of fluvoxamine, a highly selective blocker of serotonin reuptake, and desipramine, a noradrenergic agent. Eighteen patients receiving desipramine and 17 patients receiving fluvoxamine completed the study. Fluvoxamine was comparable to desipramine in its antidepressant efficacy and was better tolerated and caused minimal side effects. There was a direct linear relationship between plasma fluvoxamine levels and clinical response and a nonlinear relationship between plasma desipramine levels and clinical response. The pharmacologic specificity of the two drugs was assessed by determining uptake inhibition of serotonin and norepinephrine. The authors found a positive relationship between Hamilton Rating Scale for Depression scores and norepinephrine uptake inhibition for desipramine but found no such relationship between fluvoxamine and serotonin uptake inhibition. Although there was a clear-cut difference in the quality of pharmacologic specificity and a partial relationship to clinical response, the authors were unable to identify neuropharmacologic factors that would predict either treatment response or selective amelioration of symptomatologies in this patient population. To compare the efficacy of imipramine and fluvoxamine in inpatients from two centers suffering from a depressive disorder according to DSM IV criteria.
                The study included 141 patients with a depressive disorder according to DSM IV criteria. After a drug-free and placebo run-in period of 1 week, patients were randomized to imipramine or fluvoxamine; doses of both drugs were adjusted to a predefined target blood level. Efficacy was evaluated 4 weeks after attaining predefined adequate plasma level.
                The mean age of the study group (47 males, 94 females) was 51.8 (range 19-65) years. Of these 141 patients, 56 had episode duration longer than 1 year, 48 had mood congruent psychotic features, and 138 patients received medication. Seven patients did not complete the medication trial. The total number of patients using concurrent medication was 12/138 (8.6%). On the primary outcome criteria patients on imipramine improved significantly better on the change of illness severity score of the CGI (chi2 exact trend test=4.089, df=1, P=-0.048). There was no significant difference in 50% or more reduction on the HRSD, the other primary outcome criterion. On the secondary outcome criteria the mean reduction of the HRSD scores was significantly larger in the imipramine group than in the fluvoxamine group (mean difference=3.1, standard error (SE)=1.4, t=2.15, df=136, P=0.033). There was no significant difference in the number of patients with an HRSD < or =7 at the final evaluation.
                In depressed inpatients imipramine is more efficacious than fluvoxamine. Both drugs were well tolerated by all patients. 1. Fluvoxamine is a potent serotonin re-uptake inhibitor, with little or no noradrenergic or anticholinergic activity. 2. The results of three studies using an almost identical protocol with a prospectively randomized, double-blind design comparing fluvoxamine and chlorimipramine are presented. 3. In a population of 98 subjects suffering from a variety of depressive conditions, there was a marked improvement over four weeks in both groups. dosage was maintained between 150 and 300 mg per day. 4. There were no changes of clinical importance in vital signs, hematology or biochemistry, but pulse rates increased in the chlorimipramine group. 5. There were fewer concurrent signs and symptoms in the fluvoxamine group, especially those attributable to anticholinergic activity. The efficacy and CNS effects of the selective 5-HT re-uptake inhibitor fluvoxamine were compared with mianserin in depressed hospital out-patients in a double-blind randomized trial. Patients had to meet DSM-III criteria for Major Depressive Episode and achieve a score of at least 30 on the Montgomery-Asberg Depression Rating Scale (MADRS) after a 1-week placebo baseline period. Active treatment was for 6 weeks with an initial dose of either 100 mg fluvoxamine or 60 mg mianserin; after 1 week the dosage could be increased to 300 mg or 180 mg, respectively. Data from 63 patients (30 received fluvoxamine) were analyzed. The treatment groups were comparable with regard to age and history and severity of depression. Efficacy assessments showed similar improvements with each drug; MADRS scores improved by 65.6% with fluvoxamine and by 60.8% with mianserin. There were no significant differences between treatments at any assessment. Sedative effects were assessed using the Leeds Sleep Evaluation Questionnaire and the Digit Symbol Substitution Test. Mianserin caused a shift towards sedation in the first week in all visual analogue scales; getting to sleep and sleep quality were improved but waking was more difficult than with fluvoxamine. Similarly, the mianserin group performed less well on the Digit Symbol Substitution Test. The study confirmed that both drugs are effective treatments for depressive illness but that mianserin gives rise to sedation during the first week. 1 Two double-blind, randomised studies were performed to compare the efficacy of fluvoxamine and chlorimipramine in depressed patients. In the first study the effects of a single daily dosage of between 100 and 300 mg of fluvoxamine were compared with those of chlorimipramine at a dosage of 50-150 mg daily in 43 out-patients with endogenous depression. 2 In a second study using three times daily dosing with a daily dosage of 150-300 mg for both fluvoxamine and chlorimipramine, 30 in-patients with unipolar depression were assessed. 3 Four weeks of treatment with single daily dosing resulted in a mean improvement of 61.4% (+/- s.d. 31.7) on the Hamilton Rating Scale for Depression (HAMD) for fluvoxamine and of 65.3% (+/- s.d. 25.8) for chlorimipramine. In the study with three times daily dosing the mean results were 72.9% (+/- s.d. 22.3) improvement for fluvoxamine and 62.1% (+/- s.d. 28.5) for chlorimipramine. 4 At similar dosages, fluvoxamine had significantly less untoward effects on blood pressure than chlorimipramine. Anticholinergic effects were also fewer in the fluvoxamine group, as were nervous system symptoms, with the latter difference reaching statistical significance (P = 0.02). 5 We conclude that fluvoxamine, given in a single daily dose of 150-250 mg, provides antidepressant efficacy similar to chlorimipramine. At this dosage it may be expected to produce less anticholinergic effects and have less influence on blood pressure than chlorimipramine. The antidepressant efficacy and tolerability of milnacipran, a dual action serotonin-noradrenaline reuptake inhibitor, were compared with those of the selective serotonin reuptake inhibitor, fluvoxamine, in 113 patients with moderate to severe major depression. Treatment with milnacipran, 50 mg b.d. for 6 weeks, produced a significantly greater reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores than fluvoxamine, 100 mg b.d. (P = 0.007; 65.4% versus 49.9%, respectively); significantly greater decreases were also seen on days 7 (P = 0.04) and 28 (P = 0.03). The response rate (the proportion of patients showing a decrease in MADRS scores of at least 50%) was 78.9% in patients receiving milnacipran, compared with 60.7% in fluvoxamine-treated patients (P = 0.04). Milnacipran also produced greater improvements in 24-item Hamilton Depression Rating Scale scores (P = 0.05). On the Clinical Global Impression Improvement scale, 77.2% of milnacipran-treated patients were rated as considerably or markedly improved, compared with 60.7% of patients receiving fluvoxamine (P = 0.06 chi-squared). Both treatments were well tolerated; the only significant difference between the two groups was a higher incidence of tremor and drowsiness in patients treated with fluvoxamine. It is concluded that milnacipran may offer some advantages over selective serotonin reuptake inhibitors, such as fluvoxamine, in the treatment of moderate to severe major depression. Thirty-eight patients with primary obsessive-compulsive disorder participated in a 10-week, double-blind, placebo-controlled trial of the potent, selective serotonin reuptake inhibitor fluvoxamine. Fluvoxamine was significantly better than placebo on two of three measures of improvement in obsessive-compulsive symptoms. The authors also compared studies of the serotonergic agents fluvoxamine, sertraline, fluoxetine, and clomipramine and found that a greater effect size was associated with less serotonergic specificity and that some ability to affect other neurotransmitter systems may be a necessary but not sufficient requirement for antiobsessional activity. These data lend only partial support to a serotonin hypothesis of obsessive-compulsive disorder. Numerous neuropsychological studies have reported deficits in cognitive and attentional functioning in depressed patients. However, there are limited data available about unmedicated depressed patients and the effects of antidepressant treatment on attentional performance. In this study, a Continuous Performance Test (CPT) was employed to evaluate the attentional performance of depressed inpatients during a drugfree period (n = 52) in comparison to healthy control subjects (n = 73). After 4 weeks of double-blind treatment with imipramine (TCA) or fluvoxamine (SSRI) at adequate plasma levels the CPT performance was studied again. We found that the unmedicated patients had a significantly impaired performance on all CPT parameters (reaction time, omission errors and commission errors) in comparison to the controls. None of the CPT parameters correlated with the severity of the depression or the level of psychomotor retardation. However, the CPT performance in the patient group was significantly related to subjective mood state (depression, tension). Double-blind treatment with imipramine or fluvoxamine resulted in an improvement of the CPT performance. In the imipramine treatment group the mean reaction time decreased significantly, and after treatment with fluvoxamine a significant decrease of the mean reaction time and the number of omission errors was detected. Both antidepressants induced a significant improvement of clinical state, but we did not find a relationship between the altered CPT performance and the changes on the clinical scales. Future studies should investigate other mechanisms underlying the improved attentional performance after treatment.
                Copyright 2002 Elsevier Science Ltd. Fluvoxamine CR has been reported effective in the short-term (12-wk) treatment of generalized social anxiety disorder (social phobia). Social anxiety disorder (SAD) is, however, a chronic disorder thought to require maintenance treatment. We report on data from the extension phase of a short-term study, in order to explore the efficacy and safety profile of fluvoxamine CR (100-300 mg/d) in the longer-term treatment of this disorder. Adult outpatients with generalized social anxiety disorder (GSAD) at 35 centres in Europe, South Africa, and USA were included in an acute phase study (12 wk). Subjects who demonstrated at least minimal improvement by endpoint (n=112), were offered participation in an extension phase, in which medication was continued for a further 12 wk under double-blind conditions. Efficacy was assessed using the Liebowitz Social Anxiety Disorder Scale (LSAS), the Clinical Global Impression Global Improvement score (CGI-I), the Clinical Global Impressions Severity of Illness score (CGI-S), and the Sheehan Disability Scale (SDS). Safety and tolerability assessments were also performed at regular intervals. Subjects treated with fluvoxamine CR had a numerically greater decrease in LSAS total scores than subjects treated with placebo at endpoint. Analysis of data from baseline (day 1) to endpoint (last observation carried forward) demonstrated that this difference tended towards significance, while severity of illness on the CGI-S and disability on the SDS were significantly lower in the fluvoxamine CR group than in the placebo group. The same trends were observed when only data from weeks 12-24 were included in the analysis; although the magnitude of changes was smaller in the extension phase than in the acute phase, fluvoxamine CR-treated subjects continued to show improvement compared to placebo-treated subjects. Most treatment-emergent signs and symptoms (TESS) were mild to moderate in severity. No unexpected abnormalities were reported on vital signs, electrocardiagrams, or laboratory investigations. These data support the long-term efficacy, safety, and tolerability of fluvoxamine CR in the treatment of GSAD. Given the prevalence, persistence, and disability associated with GSAD, and the relative paucity of long-term treatment studies of SAD, the current dataset provides empirical support for the current clinical consensus that pharmacotherapy of this disorder should be continued beyond the acute phase. The aim of this 12-week, double-blind, flexible-dose, placebo-controlled, parallel-arm, multicenter trial was to determine the safety and efficacy of fluvoxamine in a controlled-release (CR) formulation in adult outpatients with obsessive-compulsive disorder (OCD).
                253 adult outpatients with DSM-IV OCD were randomly assigned to receive 100 to 300 mg of fluvoxamine CR (N = 127) or placebo (N = 126) once daily for 12 weeks. Intent-to-treat analyses of efficacy assessments with the Yale-Brown Obsessive Compulsive Scale (YBOCS), Clinical Global Impressions-Severity of Illness scale (CGI-S), and Clinical Global Impressions-Improvement scale (CGI-I) were conducted.
                Fluvoxamine CR was significantly (p <.05) superior to placebo in decreasing YBOCS total score beginning at week 2. This early response was sustained at all subsequent visits. At endpoint, there was a mean decrease of 8.5 +/- 0.7 (31.7%) in the YBOCS total score compared with baseline in the fluvoxamine CR treatment group versus a mean decrease of 5.6 +/- 0.7 (21.2%) in the placebo group (p =.001). Fluvoxamine CR was also significantly superior to placebo in lowering the severity of illness (CGI-S, p =.002) and in producing clinical improvement (CGI-I, p <.01). At endpoint, significantly greater percentages of the fluvoxamine CR treatment group were responders (p =.002) and remitters (p =.019) compared with the placebo group.
                Over 12 weeks, fluvoxamine CR treatment was associated with a statistically significant and clinically relevant reduction in OCD severity and was found to be safe and well tolerated. The early onset of therapeutic effect, starting from week 2, was of particular interest. 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. 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. 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. We investigated the relationships between the changes in plasma catecholamine metabolites obtained from depressed patients before and after administration of sulpiride, a benzamide compound, or fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), and between clinical responses to treatment with each of these drugs. Responders to sulpiride had significantly lower plasma homovanillic acid (pHVA) levels before administration of sulpiride than did non-responders or controls (responders: 4.5 +/- 3.1 ng/ml, non-responders: 11.1 +/- 5.9 ng/ml, controls: 10.9 +/- 5.3 ng/ml). Positive relationships were observed between changes in pHVA levels and improvement rates in the 17-item Hamilton Depression Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly higher plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before administration of fluvoxamine than did non-responders or controls (responders: 8.5 +/- 1.8 ng/ml, non-responders: 5.9 +/- 2.I ng/ml, controls: 5.2 +/- 2.9 ng/ml). Negative relationships were observed between changes in pMHPG levels and improvement rates in Ham-D. These results suggest that lower pretreatment pHVA levels and higher pretreatment levels of pMHPG might be predictors of response to sulpiride and fluvoxamine, respectively, and that sulpiride might produce a functional increase in the dopaminergic system, resulting in improvement in some depressive symptoms; fluvoxamine, on the other hand, might produce a functional decrease in the noradrenergic system via serotonergic neurons, resulting in improvement of those symptoms. 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. 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.
We found no strong evidence that fluvoxamine was either superior or inferior to any other antidepressants in terms of efficacy and tolerability in the acute phase treatment of depression. However, differing side effect profiles were evident. Based on these findings, we conclude that clinicians should focus on practical or clinically relevant considerations, including these differences in side effect profiles.