Gender differences in treatment response to sertraline versus imipramine in patients with nonmelancholic depressive disorders

Abstract

There is evidence of gender differences in depressive disorders in terms of epidemiology and clinical manifestations. However, few studies have addressed the gender differences in terms of antidepressant treatment response in clinical practice. The aim of this study was to examine gender differences in the acute antidepressant response to sertraline and imipramine in nonmelancholic depressive disorders. A total of 239 patients with nonmelancholic major depression or dysthymia (DSM-III-R) and a score of ≥18 at baseline on the Hamilton Depression Rating Scale (HAM-D) were randomised in a 1:1 ratio treatment with flexible doses of sertraline (50–200 mg/day) or imipramine (75–225 mg/day) for 8 weeks in a multicenter, randomised, open-labeled, parallel group comparative trial. Depressive and anxiety symptoms were assessed using the HAM-D and the Hamilton Anxiety Rating Scale (HAM-A). Using HAM-D criteria, women were significantly more likely to respond to sertraline than to imipramine (72.2% vs. 52.1%, P=.008), whilst men respond similarly to sertraline and to imipramine (56.5% vs. 59.3%, P>.05). Response analysis based on HAM-A shows similar results (women: 68.9% vs. 43.6%, P=.001; men: 56.5% vs. 51.9%, P>.05). Women taking sertraline show statistically significant higher reductions in HAM-D, HAM-A, and in CGI-S than women taking imipramine. The proportion of women who dropped out due to adverse events was much lower in sertraline than in imipramine (10.9% vs. 27.8%, P=.006), with no differences between treatments in men (8.3% vs. 11.5%, P>.05). It was concluded that sertraline is more effective and better tolerated than imipramine in the acute treatment of nonmelancholic depressive disorders in women, whereas men responded similarly to sertraline and to imipramine.

Introduction

The study of gender differences in psychiatric disorders has received increasing attention in recent years. Epidemiological studies have consistently shown that depression is about twice as common in women as in men Regier et al., 1988, Kessler et al., 1993, Weissman et al., 1993, Maier et al., 1999. There is also some evidence of gender differences in the clinical manifestations. It has been shown that depressed women appear to present a greater number of symptoms than men (Angst and Dobler-Mikola, 1984) and that they are more likely to present reverse vegetative or atypical symptoms, such as increased appetite and weight gain, as well as anxiety and somatic symptoms Kornstein, 1997, Silverstein, 1999. Some authors have also reported that depression in women tends to be more severe Thase et al., 1994, Kornstein et al., 1996 and is associated with increased functional impairment (Kornstein et al., 1996). Finally, it has also been consistently found that although women are more likely to attempt suicide, the rate of “successfully carried out” suicide is higher in men Kessler et al., 1981, Isometsa et al., 1994, Canetto and Sakinofsky, 1998, Murphy, 1998.

Although the underlying causality of this gender difference is not clear, it appears to depend on genetic, neuroanatomical, biochemical, and environmental factors Gold, 1998, Neuger et al., 1999, Ensom, 2000. Several studies have suggested that these factors could also lead to gender differences in pharmacokinetics and pharmacodynamics of antidepressant medications, such as higher plasma levels of imipramine Moody et al., 1967, Glassman et al., 1977, Hamilton et al., 1996 and amitriptyline (Preskorn and Mac, 1985) in women, as well as lower hydroxylation clearance of clomipramine (Gex-Fabry et al., 1990) and an increased volume of distribution of trazodone (Greenblatt et al., 1987). Specific gender effects on some peripheral markers of the serotonin transporter, such as the [3H]-paroxetine binding to human platelets, have also been found (Marazziti et al., 1998). Moreover, some studies have suggested that these different pharmacokinetics and pharmacodynamics could also lead to gender differences in sexual dysfunction Montejo et al., 1997, Kennedy et al., 2000 and in overall adverse event profiles (Frackiewicz et al., 2000).

Remarkably few studies have addressed the epidemiological and pharmacological implications of gender-associated differences in terms of overall treatment response to antidepressants in clinical practice. Several decades ago, it was first noted that women respond more poorly to tricyclics compared with men Raskin, 1974, Glassman et al., 1977, although poorer tolerability in women may skew these efficacy results. Recent evidence has arisen to suggest that women may respond better to selective serotonin reuptake inhibitors than men Kornstein et al., 2000, Thase et al., 2000, Martényi et al., 2001. However, the evidence for gender differences in treatment response to antidepressants is not definite Quitkin et al., 2001, Kornstein et al., 2001. In fact, recently, additional available data also suggest that no gender differences may exist in response to serotonin uptake inhibitor sertraline in panic disorder (Clayton, 2001) or to nefazodone in chronic depression (Kornstein et al., 2002).

The present study was undertaken to evaluate the comparative effectiveness and patient acceptance of sertraline versus imipramine in outpatients with nonmelancholic depressive disorders. In this article, we examine the gender differences in treatment response to both antidepressants.