Efficacy of hormone therapy with and without methyltestosterone augmentation of venlafaxine in the treatment of postmenopausal depression: a double-blind controlled pilot study.
OBJECTIVE
This study evaluated the augmentation of venlafaxine with hormone therapy in the treatment of postmenopausal depression. The hormones evaluated were estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg) and methyltestosterone (2.5 mg).


METHODS
Seventy-two menopausal women (mean age: 53.6 +/- 4.27 years) diagnosed with depression (Montgomery-Asberg Depression Rating Scale [MADRS] scores > or = 20) were treated with venlafaxine and one of the following hormone therapy combinations, in a double-blind regimen: estrogen + medroxyprogesterone + methyltestosterone (group 1, n = 20); estrogen + medroxyprogesterone acetate (group 2, n = 20); methyltestosterone only (group 3, n = 16); and no hormone therapy (group 4, n = 16). Study duration was 24 weeks. Primary efficacy outcome was remission according to the MADRS, whereas secondary efficacy measures included the Clinical Global Impression (CGI), Blatt-Kupperman Index, and Women's Health Questionnaire (WHQ).


RESULTS
Forty-eight patients completed the study. All groups showed significant improvement from baseline. Group 3 demonstrated significant improvement on the MADRS compared with placebo (group 4) at weeks 20 (P = 0.048) and 24 (P = 0.030); effect size 8.04 (0.83; 15.26) (P = 0.029), but also had the highest dropout rate. Groups 1 and 3 had significant CGI improvement rates compared with placebo: 42.23% (P = 0.012) and 44.45% (P = 0.08), respectively. There were no differences in the WHQ or BKI scores among the groups.


CONCLUSIONS
Methyltestosterone 2.5 mg had the highest effect size compared with placebo, but the high dropout rate prevented its efficacy from being determined. Estrogen plus medroxyprogesterone, combined with methyltestosterone or otherwise, demonstrated a trend toward increased efficacy of venlafaxine. Further larger-scale clinical trials are needed to elucidate the findings of this pilot study.
Dias
Rodrigo S
RS
Department of Neurology and Psychiatry, Botucatu Medical School, São Paulo, Brazil. rodrigosildias@uol.com.br
Kerr-Corrêa
Florence
F
Moreno
Ricardo A
RA
Trinca
Luzia A
LA
Pontes
Anagloria
A
Halbe
Hans W
HW
Gianfaldoni
Arlete
A
Dalben
Ivete S
IS
D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000627:therapeutic use*; D001938:Brazil; D003511:Cyclohexanols / Q000008:administration & dosage / Q000627:therapeutic use*; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D008777:Methyltestosterone / Q000008:administration & dosage*; D008875:Middle Aged; D015999:Multivariate Analysis; D010865:Pilot Projects; D017698:Postmenopause / Q000097:blood / Q000523:psychology*; D011788:Quality of Life; D012107:Research Design; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D017258:Medroxyprogesterone Acetate; D008777:Methyltestosterone; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride