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Dr. Bob is Robert Hsiung, MD,
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Posted by Iansf on December 15, 2004, at 18:46:22
Metyrapone May Be Effective as Additive Treatment of Major Depression
Laurie Barclay, MD
Medscape Medical News 2004. © 2004 Medscape
Dec. 6, 2004 — Metyrapone is effective as additive treatment for major depression, according to the results of a randomized, double-blind trial published in the December issue of the Archives of General Psychiatry.
"Alterations of the hypothalamic-pituitary-adrenal (HPA) axis are the most consistent pathological endocrine findings in depression," write Holger Jahn, MD, from the University Hospital Hamburg-Eppendorf in Germany, and colleagues. "Inhibitors of steroid synthesis have been reported to exert antidepressive effects, according to preliminary findings."
In this study, 63 inpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of major depression and a baseline score of 18 points or higher on the Hamilton Rating Scale for Depression were randomized to one of two treatment groups receiving either placebo or metyrapone, 1 g per day, for the first three weeks during a five-week treatment with standard serotonergic antidepressants (nefazodone or fluvoxamine).
The primary outcome criteria were the number of responders and the time to onset of action, defined as the time point associated with at least a 20% reduction of baseline Hamilton Rating Scale for Depression scores. Treatment response was defined as 30% reduction of baseline Hamilton Rating Scale for Depression scores after three weeks and 50% reduction after five weeks. Analysis was by intent-to-treat.
At day 21, 23 of 33 patients receiving metyrapone had a positive treatment response compared with 13 of 30 patients receiving placebo (P = .031). At day 35, there were 19 responders in the metyrapone group and 10 responders in the placebo group (P = .047).
Onset of action was earlier in the metyrapone group, beginning in the first week (P < .006). Although cortisol remained largely unchanged, the plasma concentrations of corticotrophin and deoxycortisol were higher during metyrapone treatment (P < .05). Metyrapone treatment was well tolerated without serious adverse effects.
Study limitations were a short wash-out phase and HPA-axis activity characterized solely by morning cortisol concentrations.
"Metyrapone is an effective adjunct in the treatment of major depression, accelerating the onset of antidepressant action," the authors write. "Although steroid-synthesis inhibitors are not quite ready for routine clinical application, the findings of this study clearly warrant further studies aimed at identifying subgroups of depressed patients who will benefit most from this approach and surrogate markers to find the optimal dose regimen."
One of the authors was supported by a fellowship from the Graduiertenkolleg 255 (Deutsche Forschungsgemeinschaft, Bonn, Germany). Novartis supplied the metyrapone used in this study.
Arch Gen Psychiatry. 2004;61:1235-1244
Posted by SLS on December 16, 2004, at 9:21:47
In reply to Metyrapone May Be Effective as Additive Treatment, posted by Iansf on December 15, 2004, at 18:46:22
Hi.
Thanks for the heads-up.
I read one study that claimed ketoconazole, another cortisol synthesis inhibitor, was more effective than metyrapone. I don't know how easy it would be to acquire metyrapone, as it is only used as a test to assess adrenal function. On the other hand, ketoconazole has been used for years as an anti-fungal, and is easily available. I don't know why I haven't tried it yet. I should have. I am currently looking at mifepristone (RU-486), a cortisol receptor antagonist, as a treatment for bipolar depression.
- Scott
Posted by ed_uk on December 16, 2004, at 9:45:40
In reply to Re: Metyrapone May Be Effective as Additive Treatment, posted by SLS on December 16, 2004, at 9:21:47
Hi Scott,
Metyrapone (Metopirone) capsules are available in the UK as a treatment for Cushing's syndrome. They are made by a company called Alliance. Ketoconazole has the disadvantage of occasionally causing severe hepatotoxicity.
The net price of a pack containing one hundred 250mg metyrapone caps is £42.50.Ed.
Posted by SLS on December 16, 2004, at 13:56:54
In reply to Re: Metyrapone May Be Effective as Additive Treatment » SLS, posted by ed_uk on December 16, 2004, at 9:45:40
> Hi Scott,
>
> Metyrapone (Metopirone) capsules are available in the UK as a treatment for Cushing's syndrome. They are made by a company called Alliance. Ketoconazole has the disadvantage of occasionally causing severe hepatotoxicity.
> The net price of a pack containing one hundred 250mg metyrapone caps is £42.50.
>
> Ed.
That sounds pretty good. Would you know what the dosage is for treating Cushings? I've had metyrapone on my list of things to try for awhile.
- ScottThanks.
Posted by ed_uk on December 16, 2004, at 14:11:32
In reply to Re: Metyrapone May Be Effective as Additive Treatment, posted by SLS on December 16, 2004, at 13:56:54
Hi Scott,
Here's the monograph from the BNF...
METYRAPONE
Cautions: gross hypopituitarism (risk of precipitating acute adrenal failure); hypertension on long-term administration; hypothyroidism or hepatic impairment (delayed response); many drugs interfere with diagnostic estimation of steroids; avoid in porphyria
DRIVING. Drowsiness may affect the performance of skilled tasks (e.g. driving)
Contra-indications: adrenocortical insufficiency (see Cautions); pregnancy, breast-feeding
Side-effects: occasional nausea, vomiting, dizziness, headache, hypotension, sedation; rarely abdominal pain, allergic skin reactions, hypoadrenalism, hirsutism
Dose: differential diagnosis of ACTH-dependent Cushing's syndrome, 750 mg every 4 hours for 6 doses; child 15 mg/kg (minimum 250 mg) every 4 hours for 6 doses
Management of Cushing's syndrome, range 0.25–6 g daily, tailored to cortisol production.
Ed.
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