A Comparison of Antidepressant Response in Younger and Older Women Sophie Grigoriadis, PhD, MD, FRCP(C),* Sidney H. Kennedy, MD, FRCP(C),* and R. Michael Bagby, PhD, CPsychy Abstract: The objective of this report is to compare antidepressant response rates and tolerability in younger and older women. One hundred fifteen female outpatients who met DSM-IV criteria for major depressive disorder were evaluated before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor, nefa- zodone, or venlafaxine. The sample was divided into younger and older groups based on age to approximate premenopausal and postmenopausal status. Eighty-six age-matched male outpatients formed the comparison group. Younger women compared with older women had significantly lower Hamilton Rating Scale for Depression scores after 8 weeks of antidepressant treatment and achieved significant higher rates of remission. There were no differences in overall drug tolerability. This pattern was not replicated in the male patients. Younger women with depression are more responsive to serotonergic antidepressants. This may relate to changes in menstrual status. Limitations of the study and implications for the role of female sex hormones are discussed. Future investigations should include measurement of reproductive hormone levels. (J Clin Psychopharmacol 2003;23:405–407) W omen are more prone to depression at certain points of the life cycle, although the etiologic and therapeutic implications remain largely unknown. Recently, Kornstein et al 1 reported significant differences between pre- and postmenopausal women in the rate of response to sertraline and imipramine, within a large clinical trial data set. Several decades earlier, Raskin 2 found a differential response rate to imipramine in younger versus older women but not in men. The aim of this study was to assess if differential response rates and tolerability to SSRIs and related antidepressant medications exist for younger versus older women in a ‘‘natural practice’’ clinical setting and to compare them to age-matched men. METHOD Subjects were 201 outpatients (115 female, 86 male) who consented to treatment at the Depression Clinic, Centre for Addiction and Mental Health, University of Toronto. Following a psychiatric consultation and written informed consent, trained clinicians administered the Structured Clin- ical Interview for DSM-IV Axis I Disorders, 3 the 17-item Hamilton Rating Scale for Depression 4 (HRSD), and a Side Effect Questionnaire 5 (SEQ). Patients who (a) met criteria for a nonpsychotic major depressive episode, (b) had HRSD scores 16, (c) did not have concurrent active medical illness, (d) were medication free for at least 2 weeks (5 weeks for fluoxetine), and (e) provided written informed consent to receive treatment were included in the database. This clinical protocol received approval from the local research ethics board. Selective serotonin reuptake inhibitors (SSRI), nefa- zodone, or venlafaxine was prescribed at the discretion of the treating psychiatrist at adequate doses following completion of baseline measures. Clinic psychiatrists provided standard clinical management every 2 weeks, while research staff who were unaware of medication status after 8 weeks of treatment, administered measures of HRSD and SEQ. Remission was defined as 50% reduction in HRSD-17 scores and a final HRSD score 7 after 8 weeks of treatment. The subjects were categorized by age to approximate premenopausal and postmenopausal hormonal status into younger (44 years; n = 91) or older (>50 years; n = 24) women. After 8 weeks of treatment, data were available for 77 and 22 women, respectively. Demographic information is presented in Tables 1 and 2. The younger women were more educated (t 111 = 2.1, P < 0.04), had a shorter episode duration (t 110 = 2.1, P < 0.04), and an earlier age of onset of their first Brief Report Journal of Clinical Psychopharmacology  Volume 23, Number 4, August 2003 405 *University Health Network, University of Toronto, Toronto, Ontario, Canada; yCentre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada. Received April 9, 2002; accepted after revision November 7, 2002. Address correspondence and reprint requests to Sophie Grigoriadis, PhD, MD, FRCP(C), Toronto General Hospital, University Health Network, EN8-229, 200 Elizabeth Street, Toronto, Ontario, Canada M5G 2C4. E-mail: sophie.grigoriadis@uhn.on.ca. Copyright n 2003 by Lippincott Williams & Wilkins ISSN: 0271-0749/03/2304-0405 DOI: 10.1097/01.jcp.0000085415.08426.c6 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.