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Cited by 184Treatment of Major DepressionStress Responses and CortisolTryptophan and brain disorders

Metyrapone as Additive Treatment in Major Depression: A Double-blind and Placebo-Controlled Trial

Jahn, Holger, Schick, Mildred, Kiefer, Falk, Kellner, Michael, Yassouridis, Alexander, Wiedemann, Klaus·2004·Archives of General Psychiatry
DOI 10.1001/archpsyc.61.12.1235
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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.

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  • HPA alterations are more common and more pronounced in severely depressed patients with melancholic and/or psychotic features and in elderly depressed patients.

    “they are more common and more pronounced in severely depressed patients with melancholic and/or psychotic features 68 and in elderly depressed patients 69”

    From Major depressive disorder (2016) · cites this paper as [69]

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Authors
Jahn, H., Schick, M., Kiefer, F., Kellner, M., Yassouridis, A., & Wiedemann, K.
Affiliations
  • University Medical Center Hamburg-Eppendorf (DE)
  • Max Planck Society (DE)
ORCID
Venue
Archives of General Psychiatry
Publisher
American Medical Association (AMA)
Published
2004-12-01
Volume
61
Issue
12
Pages
1235
ISSN
0003-990X (ISSN-L)
DOI
10.1001/archpsyc.61.12.1235
OpenAlex
W2095529980
Cited by
184
References
72
Citations by year
2026: 3 · 2025: 2 · 2024: 9 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 8 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 9 · 2014: 8 · 2013: 12 · 2012: 6
FWCI
8.36
Type
journal article
Language
en
Open access
closed
Locations
  • Archives of General Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
metyrapone, major depressive disorder, adjunctive therapy, nefazodone, fluvoxamine, serotonergic antidepressants, ACTH, cortisol, antidepressant response
MeSH terms
Adrenocorticotropic Hormone, Adult, Antidepressive Agents, Cortodoxone, Dehydroepiandrosterone, Depressive Disorder, Major, Major Depressive Disorder, Double-Blind Method, Drug Synergism, Drug Therapy, Combination, Enzyme Inhibitors, Female, Humans, Male, Metyrapone, Middle Aged, Piperazines, Placebos, Psychiatric Status Rating Scales, Triazoles, Fluvoxamine, Treatment Outcome

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