Controlled comparison of nefazodone and amitriptyline in major depressive inpatients

Abstract

Nefazodone, a phenylpiperazine antidepressant, exhibits novel dual activity on serotonin (5-HT) neurons; it binds to 5-HT2 receptors and inhibits 5-HT reuptake. Flexible doses of nefazodone (100-400 mg/day) and amitriptyline (50-200 mg/day) were compared in 106 major depressive inpatients in a 6-week double-blind study. Results showed significant superiority of amitriptyline over nefazodone on all rating instruments: Montgomery and Asberg depression rating scale (P < 0.0001), Hamilton depression scale (P < 0.0006), Clinical Global Impressions (P < 0.0001) and Patient Global Assessment (P < 0.01). A total of 65% of patients under amitriptyline and 56% of patients under nefazodone reported adverse events during the study, with significantly more dry mouth in the amitriptyline group (39% versus 11%, P = 0.001). Modal daily doses within the last treatment week reached 242 mg with nefazodone and 124 mg with amitriptyline. The lower efficacy of nefazodone, which contradicts comparative trials with imipramine in US patients, is discussed with regard to the dose of nefazodone, probably below the optimal therapeutic range for melancholic patients, and to the clinical differences between the patient samples.

Nefazodone in Psychotic Unipolar and Bipolar Depression: A Retrospective Chart Analysis and Open Prospective Study on Its Efficacy and Safety versus Combined Treatment with Amitriptyline and Haloperidol

“…Several studies comparing NEF with imipramine found equal efficacy [9][10][11][12]; the same holds true for another study versus AMI [13].…”

North of England evidence-based guideline development project: summary version of guidelines for the choice of antidepressants for depression in primary care

“…Analysis of the comparative efficacy of SSRIs and tricyclic antidepressants in in-patients (judged likely to be a more severely affected group) provided a slightly larger estimate of effect favouring tricyclic antidepressants, though again non-significant. The overall estimate of effect in this grouping of studies 8,16,27,35,44,47,67,69,73,74,77,80,81,82,86,88,91,94,98,99,105,108,111,118,120,127 (using a random effects model) was 0.10 (95% CI -0.072 to 0.272, Q = 49.1, d.f. = 22, P = 0.008).…”

Efficacy of selective serotonin reuptake inhibitors in the absence of side effects: a mega-analysis of citalopram and paroxetine in adult depression

“…10 Supporting the assumption that antidepressants do not act merely by means of a placebo effect, depressed patients were treated with drugs, including central stimulants, barbiturates, opiates and antipsychotics, but without satisfactory effect, 30 even before the serendipitous discovery of the first antidepressants, imipramine and iproniazide; 31 had drug treatment of depression been merely a matter of a psychological placebo response, these compounds should have appeared just as effective as imipramine or iproniazide. Moreover, a large number of trials have revealed significant differences between two antidepressants (or putative antidepressants) in trials including no placebo arm; [32][33][34][35][36] had the superiority of antidepressants over placebo in controlled trials been merely the result of the patient realizing that he/she has not been given active treatment, such an outcome would be difficult to explain given that the participants in these trials knew that they were not at risk of receiving placebo. The present data, suggesting that antidepressants do not act merely by means of a placebo effect, are well in line with these observations.…”