Gender differences in treatment response to sertraline versus imipramine in chronic depression

Am J Psychiatry. 2000 Sep;157(9):1445-52. doi: 10.1176/appi.ajp.157.9.1445.


Objective: The authors examined gender differences in treatment response to sertraline, a selective serotonin reuptake inhibitor (SSRI), and to imipramine, a tricyclic antidepressant, in chronic depression.

Method: A total of 235 male and 400 female outpatients with DSM-III-R chronic major depression or double depression (i.e., major depression superimposed on dysthymia) were randomly assigned to 12 weeks of double-blind treatment with sertraline or with imipramine after placebo washout.

Results: Women were significantly more likely to show a favorable response to sertraline than to imipramine, and men were significantly more likely to show a favorable response to imipramine than to sertraline. Gender and type of medication were also significantly related to dropout rates; women who were taking imipramine and men who were taking sertraline were more likely to withdraw from the study. Gender differences in time to response were seen with imipramine, with women responding significantly more slowly than men. Comparison of treatment response rates by menopausal status showed that premenopausal women responded significantly better to sertraline than to imipramine and that postmenopausal women had similar rates of response to the two medications.

Conclusions: Men and women with chronic depression show differential responsivity to and tolerability of SSRIs and tricyclic antidepressants. The differing response rates between the drug classes in women was observed primarily in premenopausal women. Thus, female sex hormones may enhance response to SSRIs or inhibit response to tricyclics. Both gender and menopausal status should be considered when choosing an appropriate antidepressant for a depressed patient.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Ambulatory Care
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Chronic Disease
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / psychology
  • Double-Blind Method
  • Dysthymic Disorder / diagnosis
  • Dysthymic Disorder / drug therapy
  • Dysthymic Disorder / psychology
  • Estrogens / physiology
  • Female
  • Humans
  • Imipramine / therapeutic use*
  • Male
  • Middle Aged
  • Patient Dropouts
  • Placebos
  • Premenopause / physiology
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Sertraline / therapeutic use*
  • Severity of Illness Index
  • Sex Factors
  • Treatment Outcome


  • Antidepressive Agents, Tricyclic
  • Estrogens
  • Placebos
  • Serotonin Uptake Inhibitors
  • Imipramine
  • Sertraline