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Arch Gen Psychiatry. 2004 Dec;61(12):1235-44.

Metyrapone as additive treatment in major depression: a double-blind and placebo-controlled trial.

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  • 1Department of Psychiatry and Psychotherapy, University Hospital Hamburg-Eppendorf, Hamburg, Germany. jahn@uke.uni-hamburg.de

Abstract

BACKGROUND:

Inhibitors of steroid synthesis have been reported to exert antidepressive effects, according to preliminary findings.

OBJECTIVE:

To test whether the addition of metyrapone to standard antidepressants induces a more rapid, more efficacious, and sustained treatment response in patients with major depression.

DESIGN:

Double-blind, randomized, placebo-controlled trial.

SETTING:

Hospitalized care.

PATIENTS:

Sixty-three inpatients with a DSM-IV diagnosis of major depression and a baseline score 18 points or higher on the Hamilton Rating Scale for Depression.

INTERVENTIONS:

Random allocation to 2 treatment groups receiving either placebo or metyrapone (1 g/d) for the first 3 weeks during a 5-week treatment with standard serotonergic antidepressants (nefazodone or fluvoxamine).

MAIN OUTCOME MEASURES:

Primary outcome criteria were the number of responders and the time to onset of action. Responder rates were considered twice after 3 and 5 weeks with a definition of treatment response as 30% and 50% reduction, respectively, of baseline Hamilton Rating Scale for Depression scores. Onset of action was defined as the time point at which at least a 20% reduction of baseline Hamilton Rating Scale for Depression scores occurred.

RESULTS:

Using intention-to-treat analysis, we found that a higher proportion of patients receiving metyrapone showed a positive treatment response at day 21 (23 of 33 patients) and at day 35 (19 of 33 patients) compared with placebo patients (day 21: 13 of 30 patients; Fisher exact P = .031; day 35: 10 of 30 patients; Fisher exact P = .047). The clinical course of patients treated with metyrapone showed an earlier onset of action (Kaplan-Meier analysis; log-rank test P<.006) beginning in the first week. The plasma concentrations of corticotropin and deoxycortisol were significantly higher during metyrapone treatment (multivariate analysis of covariance, P<.05), whereas cortisol remained largely unchanged. Metyrapone treatment was well tolerated without serious adverse effects.

CONCLUSIONS:

Metyrapone is an effective adjunct in the treatment of major depression, accelerating the onset of antidepressant action. A better treatment outcome compared with standard treatment and a sustained antidepressive effect were observed.

PMID:
15583115
[PubMed - indexed for MEDLINE]
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