Progress in Neuro-Psychopharmacology and Biological Psychiatry
Gender differences in treatment response to sertraline versus imipramine in patients with nonmelancholic depressive disorders
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.
Section snippets
Patient population
Outpatients of both genders, aged 18 or over, not suffering from significant concomitant diseases, and with a DSM-III-R (American Psychiatric Association, 1987) diagnosis of nonmelancholic major depression or dysthymia were eligible for participation in the study. Patients were required to have a score of at least 18 at baseline on the 21-item Hamilton Depression Rating scale (HAM-D21) Hamilton, 1960, Hamilton, 1967.
Patients were excluded (1) if they fulfilled the criteria for meeting DSM-III-R
Subjects characteristics
A total of 239 patients (i.e., the safety population) from 12 centres in Spain entered the study, 116 in the sertraline group and 123 in the imipramine group. Of these 239 patients, 3/116 in sertraline (2.6%) and 2/123 in imipramine (1.6%) were excluded from the effectiveness analysis for not having at least one effectiveness data after treatment initiation, leaving a total of 234 patients included in the effectiveness analysis. Table 1 shows the sociodemographic and clinical characteristics of
Discussion
The aim of the study was to examine gender differences in the acute antidepressant response to sertraline and imipramine in nonmelancholic depression. The results show that men responded similarly whether assigned to sertraline or imipramine, whilst women assigned to sertraline were more likely to respond well—and to remit—to treatment. This result may be attributed to the differential tolerability profile of sertraline and imipramine in women. Whilst men showed similar dropout rates
Conclusions
The study results point out that there are gender differences in the effectiveness and tolerability of antidepressants in the treatment of nonmelancholic depression. Specifically, sertraline is more effective and better tolerated than imipramine in the acute treatment of nonmelancholic depression in women with an earlier and higher response for anxiety symptoms, whereas men responded similarly whether assigned to sertraline or imipramine. However, further studies are needed in order to have
Acknowledgements
The authors wish to thank additional investigators and collaborating sites: M.González de Chávez (Hospital Gregorio Marañón, Madrid); S. Oliveros (Hospital Puerta de Hierro, Madrid); B. Franco (C.S.M. Colmenar Viejo, Madrid); A. Rivera, B. Penasa, and I. López (C.S.M. Salamanca, Madrid); E. Capdevila (Centro de Psiquiatrı́a y Psicoterapia, Madrid); F. Pérez Arnau and F. Teba (C.S.M. Prat de Llobregat, Barcelona); C. Gastó, J. Blanch, and L. Pintor (Hospital Clinic, Barcelona); J. Pérez de los
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