Are gender differences important for the clinical effects of antidepressants?
OBJECTIVE
Gender differences in antidepressant treatment response, side effects, dropout rates, and plasma concentrations were examined in patients with major and predominantly melancholic depression.


METHODS
The study included a subgroup of 292 inpatients (96 men, 196 women) from three Danish double-blind, randomized, controlled trials. All patients completed a 5-week treatment period and fulfilled the DSM-III or DSM-III-R criteria for major depression. Clomipramine (150 mg/day) was the reference treatment, and comparable treatments were citalopram (40 mg/day), paroxetine (30 mg/day), and moclobemide (400 mg/day). Assessments were performed by using the 17-item Hamilton Depression Rating Scale and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. In a subgroup of 110 patients, weekly measurements of clomipramine plasma concentrations were obtained. Nonparametric statistical tests and multiple linear and logistic regression models were used for statistical evaluations.


RESULTS
Both genders had similar remission rates (Hamilton depression scale score <8) when treated with clomipramine and had significantly higher remission rates with clomipramine than with the comparable treatments. The plasma concentrations of clomipramine were significantly higher for female than for male patients. No gender differences were found in posttreatment Hamilton depression scale scores, nor did the therapeutic effects of treatment depend on gender. Rates of dropout and side effects were similar for men and women. No relationship between plasma concentrations, gender, and therapeutic outcome was found.


CONCLUSIONS
In a group of patients with major and predominantly melancholic depression, differentiation according to gender was not important in treatment with common antidepressants. Women appeared to have higher plasma concentrations of tricyclic antidepressants than men. The consequences of this difference for clinical effects are unclear. Gender-specific recommendations for dosing of tricyclic antidepressants may be considered.
Hildebrandt
Malene Grubbe
MG
Department of Psycchiatry, Center for Depression Research, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense C, the Netherlands. malenehdk@yahoo.com
Steyerberg
Ewout Willem
EW
Stage
Kurt Bjerregaard
KB
Passchier
Jan
J
Kragh-Soerensen
Per
P
D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D002997:Clomipramine / Q000493:pharmacokinetics / Q000627:therapeutic use; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D010352:Patient Dropouts; D010597:Pharmacogenetics; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D012737:Sex Factors; D016896:Treatment Outcome
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine; D008996:Monoamine Oxidase Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors