Men and women with chronic major depression
responded differently to sertraline and imipramine

Kornstein SG, Schatzberg AF, Thase ME, et al. Gender differences in treatment response to sertraline versus imipramine in
chronic depression.
Am J Psychiatry 2000 Sep;157:1445–52.

QUESTION: Do men and women with chronic depression have different treatment
responses to selective serotonin reuptake inhibitors (SSRIs) (eg, sertraline) and tricyclic
antidepressants (TCAs) (eg, imipramine)?
Randomised {allocation concealed*}†, blinded {clini- Patients were allocated to sertraline, 50 mg/day initially cians, patients, and outcome assessors}†*, controlled (n = 264 women and 162 men) or imipramine, 50 mg/ day initially (n = 136 women and 73 men). Doses could be increased to a maximum of 200 mg/day for sertraline(mean dose 139.6 mg/d for women; 143.2 mg/d for men) and a maximum of 300 mg/day for imipramine (mean 10 university medical centres and 2 clinical research dose 196.3 mg/d for women; 207.5 mg/d for men).
Main outcome measures
Dropout rates and treatment response (50% decrease in Patients
Hamilton Depression Rating Scale [HDRS] score, HDRS 400 women (mean age 40 y) and 235 men (mean age 43 score <15, a Clinical Global Impression [CGI] severity scale y) who were 21–65 years of age and met DSM-III-R cri- score <3, and a CGI improvement scale score of 1 or 2).
teria for chronic major depression or double depres- 23298-0710, USA.
Fax +1 804 828
sion. Follow up was 80%; analysis of all patients was Main results
done using last observation carried forward.
A statistically significant interaction effect was foundbetween treatment and sex for rates of dropout Sertraline and imipramine for chronic major depression at 12 weeks‡ (p = 0.009) and treatment response (p = 0.001). Women Table 1 Sertraline v imipramine in women taking sertraline had lower dropout rates than women Outcomes
RRR (95% CI)
taking imipramine (p = 0.002), whereas no difference wasseen between groups among men (table 1 and 2 ).
Women had a greater response rate in the sertraline group than in the imipramine group (p = 0.02), and men had a greater response rate in the imipramine groupthan in the sertraline group (p = 0.04) (table 1 and 2 ).
Table 2 Imipramine v sertraline in men Conclusions
In patients with chronic depression, sertraline was moreeffective than imipramine and led to fewer dropouts in women; imipramine was more effective than sertraline ‡Abbreviations defined in glossary; RRR, RBI, NNT, and CI calculated from data in article.
As we all know, men and women are different. One of these sex differences occurs in mood disorders: depression is approximately twice as common in womenas men. Mood disorder in women is also a subject of serious academic study and the focus of a major new textbook.1 The increase in depression rates inwomen becomes evident after puberty, and it is argued that the difference lessens after menopause. Given these findings, sex based differences in treatmentresponse are of great interest. Such differences are important because unipolar depression is such a large public health problem, ranking second in devel-oped market economies in recent global burden of disease studies.2 Previous studies have suggested that women might be more responsive to serotonergic agents, and the study by Kornstein et al is a timely addition to this literature. It shows fairly convincingly that women have a better response to SSRIs and men a better response to TCAs. The authors comment on the possi-ble reasons for this, especially because the differing response rate was observed primarily in premenopausal women. Obviously, the female sex hormones andthe menstrual cycle may play a role in determining this phenomenon.
This finding has potentially important implications for clinical practice. Although reasons still exist (eg, side effect profile, safety in overdose) to choose an SSRI as a first line agent in men, this study reminds us that TCAs may still have a place in psychiatry, and that sex should be added to the list of factors toconsider when selecting an antidepressant. This study was completed under contract from Pfizer Pharmaceuticals, the makers of sertraline, and this articlemay enhance the sales profile of sertraline. The relationship between the pharmaceutical industry and medical academics has recently come under the spot-light.3 Because of the clear commercial implications and potentially increased healthcare costs, it is important that this study be independently replicated.
Allan H Young, MBChB, MPhil, PhD, MRCPsych Royal Victoria Infirmary, University of Newcastle 1 Steiner M, Yonkers KA, Eriksson E. Mood disorders in women. London: Martin Dunitz, 2000;573.
2 Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: global burden of disease study. Lancet 1997;349:1436–42.
3 Jackson T. Marketing: are you being duped? BMJ 2001:322:1312.
Men and women with chronic major
depression responded differently to sertraline
and imipramine

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