Posted by Iansf on February 16, 2005, at 18:32:24
Feb. 8, 2005 — Dehydroepiandrosterone (DHEA) can be effective for midlife-onset minor and major depression, according to the results of a placebo-controlled, randomized trial published in the February issue of the Archives of General Psychiatry.
"Alternative and over-the-counter medicines have become increasingly popular choices for many patients who prefer not to take traditional antidepressants," write Peter J. Schmidt, MD, from the National Institute of Mental Health in Rockville, Maryland, and colleagues. "The adrenal androgen and neurosteroid DHEA is available as over-the-counter hormonal therapy and previously has been reported to have antidepressant-like effects."
This double-blind, crossover-design treatment study took place from Jan. 4, 1996, through Aug. 31, 2002, at the National Institute of Mental Health Midlife Outpatient Clinic. In this trial, 23 men and 23 women aged 45 to 65 years with midlife-onset major or minor depression were randomized to six weeks of DHEA therapy, 90 mg/day, for three weeks and 450 mg/day for three weeks or to six weeks of placebo followed by six weeks of the other treatment. The subjects did not receive any other antidepressant medications during the study.
Primary outcomes were the 17-Item Hamilton Depression Rating Scale (HDRS-17) and Center for Epidemiologic Studies Depression (CESD) Scale, and secondary outcomes included the Derogatis Interview for Sexual Functioning (DISF).
DHEA treatment for six weeks was associated with improvement in both primary outcome measures compared with both baseline (P< .01) and with six weeks of placebo (P< .01). After DHEA treatment, 23 subjects had a 50% or greater reduction in baseline HDRS-17 scores, as did 13 subjects after placebo treatments. DISF scores relative to baseline and placebo conditions also improved significantly after six weeks of DHEA treatment. The treatment with DHEA was well-tolerated.
"We find DHEA to be an effective treatment for midlife-onset major and minor depression," the authors write. "Despite initial suggestions of a sexual dimorphism in the therapeutic actions of DHEA, the response to DHEA did not differ between men and women."
Study limitations include lack of data in severe major depression, inability to confirm the superior efficacy of the larger dosage of DHEA, and possible confounding by carryover effects.
"As a caution, the use of DHEA in the treatment of patients with antidepressant-resistant depression has not been determined, and the magnitude of the antidepressant effects of DHEA compared with those of traditional antidepressants needs to be empirically demonstrated," the authors conclude. "As a final caveat, the long-term effects of DHEA have not been fully documented. The potential to exacerbate or initiate hormone-responsive tumors exists, and those prescribing DHEA should familiarize themselves with the means to evaluate a patient for DHEA therapy and to monitor DHEA therapy appropriately."
Arch Gen Psych. 2005;62:154-162
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
Evaluate the effect of DHEA as monotherapy for major and minor depression at midlife in men and women.
Compare responses to DHEA for midlife depression in men vs women.
Clinical Context
Alterations in DHEA secretion have been suggested as a possible etiologic factor for midlife depression, and mood-elevating effects of DHEA have been observed in both men and women with and without depression. DHEA is available as an over-the-counter alternative medicine. The mechanism of action of DHEA may be associated with action at the androgen receptor, but the existence of dimorphism in treatment response is unclear. Studies have been conflicting in findings related to administration of DHEA to aging men with low DHEA levels and in perimenopausal and postmenopausal women. According to the authors, past studies of DHEA effects on depression have included heterogeneous groups of patients and used varying dosages of DHEA. Also, predictors of a DHEA response including sex have not been identified.
The current authors conducted a randomized, double-blind, crossover trial of DHEA in two dosages (low dose for three weeks followed by high dose for three weeks) to examine effects on mild to moderate minor and major depression in men and women and to find predictors of DHEA response.
Study Highlights
Inclusion criteria were men and women aged 40 to 65 years with depression onset within 5 years, symptom-free for at least two years before the current episode with no history of DHEA treatment, and free of antidepressant and hormonal medications for 4 months. 4 patients had partially responded to antidepressants in the past and requested alternative therapy.
Exclusion criteria were major depression greater than moderate severity, prostatism, family history of breast cancer, systemic illness, abnormal mammogram, and abnormal laboratory results.
At baseline patients were screened with the HDRS-17, Beck Depression Inventory (BDI), and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. They met criteria for dysthymia and minor or major depression, with scores of at least 10 on the HDRS-17 or BDI.
52 patients (28 women and 24 men) were randomized to receive either DHEA or placebo first. 23 men and 23 women completed the study.
Each treatment phase lasted 6 weeks with a one- to two-week washout before crossover. DHEA treatment consisted of 3 weeks at low dose (30 mg 3 times a day) followed by 3 weeks at high dose (150 mg 3 times a day). Placebo appeared identical, and duration was 6 weeks.
All women received 10 days of 5 mg of medroxyprogesterone acetate at the end to cause menses due to endometrial stimulation.
Blood samples of DHEA, DHEA sulfate, total testosterone, free testosterone, sex-hormone-binding globulin, estradiol, and androgen metabolites were drawn at baseline and week 6 of each phase.
Primary outcomes were depression rating on the HDRS-17 and Center for Epidemiologic Studies Depression Scale (CES-D).
Secondary outcomes were the BDI Scale, modified Cornell Dysthymia Scale (CDS), and modified DISF.
Analysis was per protocol.
Mean age was 50 years, 75% were married, mean body mass index was 25 kg/m2, and few smoked.
17% of women and 61% of men had minor depression. 83% of women and 39% of men had major depression. Baseline HDRS-17 score was 14.3 in women and 12.7 in men. Baseline CES-D score was 27.0 in women and 24.7 in men.
DHEA significantly improved mood scores compared with baseline and placebo on the HDRS-17 (P< .001). DHEA vs baseline was P< .01; and DHEA vs placebo, P< .01.
CES-D scores were significantly improved in the DHEA compared with baseline and placebo phase (P< .001). DHEA vs baseline was P< .01; and DHEA vs placebo, P< .01.
DHEA vs placebo differences were less robust by the BDI and CDS.
Total DISF scores were significantly improved in the DHEA phase relative to baseline (P< .05) and placebo (P< .01).
Sex did not affect outcomes.
23 subjects (12 women and 11 men) had a 50% or greater response on the HDRS-17 scores vs 13 subjects receiving placebo.
12 (43%) of the 28 subjects with major depression were classified as responders vs 11 (61%) of 18 subjects with minor depression.
There was no significant effect of past major depression on HDRS-17 scores.
Plasma levels of DHEA, DHEA sulfate, androstendione, and 3a-androstanediol glucuronide increased significantly after DHEA treatment in men and women.
Sex, reproductive status, baseline mood ratings, blood hormone levels at baseline, and change in hormone levels did not predict response to DHEA. There was lack of association between DHEA level and antidepressant response to DHEA.
13 responders to DHEA chose to continue open-label over-the-counter DHEA treatment (at 25-50 mg daily) after the trial was completed. 10 remained asymptomatic for up to 12 months of follow-up.
Adverse events were minor with acne or oily skin being most common.
poster:Iansf
thread:458971
URL: http://www.dr-bob.org/babble/alter/20050131/msgs/458971.html