Fluvoxamine and clomipramine in depressed patients A DOUBLE‐BLIND CLINICAL STUDY

Abstract

In a double-blind study we compared fluvoxamine, a new selective serotonin re-uptake inhibitor, with clomipramine. In 36 female inpatients with vital depression, the antidepressant properties of fluvoxamine and clomipramine were studied. Eight patients did not complete the study. During a 4-week treatment period the Hamilton-, Zung-, Clinical Global Impression- and Leyden ratings showed, apart from the last scale in the fluvoxamine group, significant improvement in both groups. In the latter scale, a statistically significant difference was found in favour of clomipramine. Additional anxiolytic-sedative medication was required equally in both groups. CSF data in 10 patients are discussed. Non-specific electrocardiographic (ECG) repolarization disturbances were observed in both groups. Anticholinergic side effects were more prominent with clomipramine than with fluvoxamine; gastrointestinal symptoms and agitation were more prominent with fluvoxamine than with clomipramine. Fluvoxamine did not show particular advantages or disadvantages over clomipramine.

A placebo controlled study of the cardiovascular effects of fluvoxamine and clovoxamine in human volunteers.

“…The these studies confirm the safety and tolerance as well as the predicted antidepressant effects (Doogan, 1980;Saletu et al, 1977;Wright & Derlber, 1978;Klok et al, 1981;Freeman et al, 1981). The maximum doses of fluvoxamine and clovoxamine prescribed in human experiments have been 400 mg/day.…”

Fluvoxamine by itself has potential to directly induce long QT syndrome at supra-therapeutic concentrations

“…While only one clinical case of fluvoxamine-induced torsade de pointes has been reported (Manet et al, 1993), bradycardic action (de Wilde et al, 1983;Granfors et al, 2004;Pacher and Kecskemeti, 2004;Saletu et al, 1977), QT-interval prolongation (Klok et al, 1981;Nia et al, …”

“…in guinea pigs (Ohtani et al, 2001). It should be noted that in some previous clinical studies (Klok et al, 1981;Nia et al, 2012), the QT interval was prolonged by clinical doses of fluvoxamine; however, such prolongation was not observed in the other clinical reports (Beach et al, 2014;Okayasu et al, 2012). Since fluvoxamine prolonged the QT interval in a dose-related manner in this study, one can speculate that the discrepancy among the previous reports might in part depend on the difference of the plasma free drug concentration and/or concomitant use of other drugs.…”

“…Moreover, fluvoxamine by itself was reported to inhibit human ether-a-go-go-related gene (hERG) channels (Milnes et al, 2003). Indeed, in some previous clinical studies (Klok et al, 1981;Nia et al, 2012), the QT interval was prolonged by clinical doses of fluvoxamine; however, such prolongation was not observed in the other clinical reports (Beach et al, 2014;Okayasu et al, 2012). Furthermore, specific data are very limited regarding the proarrhythmic effects of fluvoxamine (Claassen, 1983;Manet et al, 1993;Wouters and Deiman, 1983).…”

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).…”