Are there gender differences in major depression and its response to antidepressants?

Journal of Affective Disorders 75 (2003) 223–235 www.elsevier.com / locate / jad

Research report

Are there gender differences in major depression and its response to antidepressants? a b c c, Susanne Scheibe , Claudia Preuschhof , Carolina Cristi , R. Michael Bagby * a

Max Planck Institute for Human Development, Berlin, Germany b Humboldt University, Berlin, Germany c Section on Personality and Psychopathology, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, M5 T 1 R8, Canada Received 18 August 2000; accepted 4 January 2002

Abstract Background: The prevalence of major depression for women is about twice that for men. This gender difference in prevalence rates has led to much research addressing gender differences in the presentation and features of major depression, and, to a lesser extent, research addressing gender differences in treatment response and personality. However, studies differ considerably in the population sampled, and findings vary significantly. In the current retrospective examination of data, we investigated all of these variables in one single sample of outpatients with major depression seen in a tertiary care centre. Methods: A sample of 139 men and 246 women with major depression receiving antidepressant treatment (SSRIs, TCAs, SNRIs, MAOIs, or RIMAs) in an outpatient setting were contrasted with regard to symptoms and severity of depression, course of illness, treatment response, and personality. Results: Women were found to experience more vegetative and atypical symptoms, anxiety, and anger than men, and to report higher severity of depression on self-report measures. Regarding personality, women scored higher on conscientiousness, the extraversion facet warmth, the openness facet feelings, and sociotropy. Effect sizes were small to moderate. No differences were found in the course of the illness and treatment response. Limitations: Findings are not generalizable to inpatient or community samples, and some of the gender differences may be accounted for by gender differences in treatment seeking behaviour. Conclusions: While men and women receiving antidepressant treatment show some gender differences in the psychopathology of major depression, these differences do not appear to translate into differences in response to antidepressants. Gender differences in personality appear less profound than in the average population, indicating the potential role of a certain personality type that predisposes individuals to develop clinical depression, independent of gender. Clinical relevance: The current examination underscores the role gender plays in the presentation and treatment of major depression.  2002 Elsevier B.V. All rights reserved. Keywords: Depression; Gender; Personality; Treatment response

*Corresponding author. Tel.: 1 1-416-535-8501x6939; fax: 1 1-416-979-6821. E-mail address: michael [email protected] (R.M. Bagby). ] 0165-0327 / 02 / $ – see front matter  2002 Elsevier B.V. All rights reserved. doi:10.1016/S0165-0327(02)00050-2

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1. Introduction Women are at higher risk to develop depressive disorders than are men. Empirical investigations over a period of more than 20 years have demonstrated that women are typically twice as likely to develop depressive disorders than men are (Weissman and Klerman, 1977; Kessler et al., 1993; Weissman et al., 1993), although this ratio has been reported to vary across different types of depressive disorders (Perugi et al., 1990). For example, while women are two times more likely to develop a single episode unipolar depression, they are four times more likely to develop recurrent unipolar depression (Perugi et al., 1990). These ratios have been reported in a wide range of patient and non-patient populations, including clinical and community samples with major depression, and community samples with sub-threshold depressive symptoms (e.g., Weissman and Klerman, 1977; Oldehinkel et al., 1999). While the preponderance of women suffering from depressive disorders is well-established and frequently replicated, considerably less attention has been given to gender differences in the presentation and features of depression. This related line of research has attempted to determine empirically whether, and in what specific aspects, depression in men differs from depression in women (Angst and DoblerMikola, 1984; Frank et al., 1988; Perugi et al., 1990; Thase et al., 1994; Kornstein et al., 1995, 2000a,b; Rapaport et al., 1995; Zlotnick et al., 1996; Simpson et al., 1997; Bracke, 1998; Silverstein, 1999). Gender differences have been reported in severity and symptoms of depression, course of illness, and treatment response in some of these studies, while other studies reported negative results. Few studies have also examined the differences in the personality traits of depressed men and women. However, these studies differ considerably in terms of the population sampled, which may have contributed to inconsistent findings across these different studies. For example, while some studies have investigated community samples of individuals with sub-threshold clinical depression (e.g., Angst and Dobler-Mikola, 1984; Bracke, 1998), other studies have included depressed patients meeting full diagnostic criteria (e.g., Thase et al., 1994; Fava et al., 1996; Silverstein, 1999). Several clinical studies have included both unipolar

and bipolar depressed patients (Frank et al., 1988; Perugi et al., 1990; Rapaport et al., 1995; Croughan et al., 1988; Simpson et al., 1997), which are likely to have contributed to inconsistent findings. Other studies have investigated quite narrowly defined populations, such as samples with chronic depression (i.e., longer than 2 years) (Kornstein et al., 1995, 2000a,b), recurrent depression (i.e., at least two previous episodes) (Frank et al., 1988), or pure depression (i.e., exclusion of individuals with comorbid Axis I disorders) (Sotsky et al., 1991; Kornstein et al., 1995; Zlotnick et al., 1996). One goal of this paper was to review systematically the literature on gender differences and depression with respect to symptoms, severity, course of illness, personality, and treatment response, with particular attention to the different populations sampled. As none of the reviewed studies examined all of these variables in a single sample, resulting, perhaps, in inconsistent findings, a second goal was to investigate all of these potential factors related to gender differences in depression in one sample of unipolar depressed patients receiving antidepressant treatment. We believe that such an analysis provides a more cohesive and meaningful depiction of gender and depression, at least for those depressed persons receiving treatment.

1.1. Types of symptoms In a community sample of individuals with dysphoric mood, Angst and Dobler-Mikola (1984) found that women reported more appetite and sleep disturbances, while men reported more psychomotor changes, feelings of worthlessness, and decreased concentration. Silverstein (1999) reported that clinically depressed women in the general population exhibited a higher number of somatic symptoms including fatigue, sleep and appetite disturbance. Accordingly, in clinical in- and outpatient populations, women were reported to be more likely to have vegetative and / or atypical symptoms such as increased appetite, weight gain, and sleep disturbance (Frank et al., 1988; Perugi et al., 1990; Young et al., 1990). Clinically depressed women were also reported to show higher levels of anxiety and somatization (Frank et al., 1988; Perugi et al., 1990; Kornstein et al., 1995, 2000a), as well as anger

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(Frank et al., 1988) and psychomotor retardation (Kornstein et al., 1995, 2000a). One study of clinically depressed individuals reported that men are more likely to endorse weight loss (Frank et al., 1988). A study of recurrently depressed individuals that weighed patients during and between episodes only found a trend toward men losing more weight than women (Stunkard et al., 1990).

1.2. Severity of depression Women with clinical depression may tend to experience a greater severity of depressive symptoms (Frank et al., 1988; Perugi et al., 1990; Thase et al., 1994; Kornstein et al., 1995, 2000a). Women with sub-threshold depression have also been reported to endorse a greater overall number of depressive symptoms (Angst and Dobler-Mikola, 1984; Bracke, 1998). Other clinical studies failed to find a gender difference in depression severity (Croughan et al., 1988; Young et al., 1990; Fava et al., 1996; Bothwell and Scott, 1997). Perugi et al. (1990) pointed out that gender differences are especially prominent in the self-reported severity of depressive symptoms as compared to interview-based measures of depression severity. Accordingly, Frank et al. (1988) and Kornstein et al. (2000a) reported that women presented as more severely depressed than men on the Beck Depression Inventory (BDI; Beck, 1978), while this difference was absent on the clinician-rated Hamilton Rating Scale for Depression (HRSD; Hamilton, 1967).

1.3. Course of depression Some studies reported that women have an earlier age of onset of the first depressive episode (Ernst and Angst, 1992; Kornstein et al., 1995, 2000a; Fava et al., 1996), whereas other studies found no difference (Amenson and Lewinsohn, 1981; Frank et al., 1988; Perugi et al., 1990; Thase et al., 1994; Rapaport et al., 1995; Simpson et al., 1997). In community samples, it was found that depression in women is more likely to develop into a recurrent course (Amenson and Lewinsohn, 1981; Ernst and Angst, 1992; Bracke, 1998). However, most studies using clinical samples do not find a gender difference in the number of previous depressive episodes

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(Frank et al., 1988; Winokur et al., 1993; Kornstein et al., 1995, 2000a; Bothwell and Scott, 1997). In addition, depression in women has been reported to be more chronic in community samples (Sargeant et al., 1990; Bracke, 1998) and in patients with pure depression (i.e., without comorbid Axis I disorders) (Keitner et al., 1991). However, again this gender effect in chronicity of depression was absent in other clinical studies (e.g., Amenson and Lewinsohn, 1981; Perugi et al., 1990; Winokur et al., 1993; Kornstein et al., 1995, 2000a; Rush et al., 1995). Moreover, in a prospective study following patients with a first episode of major depression for 15 years, Simpson et al. (1997) found no evidence of a more chronic or recurrent course in women.

1.4. Antidepressant treatment response Gender may be an important variable in understanding variability of response to antidepressant treatment. There is some evidence that women respond more poorly than men to tricyclic antidepressants (TCAs), with imipramine studied the most. For example, Frank et al. (1988) reported that men with recurrent major depression have a more rapid and sustained response to imipramine than women. In a recent study, Kornstein et al. (2000b) found that chronically depressed men responded more favourably to imipramine than women, while women showed a more favourable response to sertraline [a selective serotonin re-uptake inhibitor (SSRI)] than men. Haykal and Akiskal (1999) further found that females diagnosed with dysthymia and treated with fluoxetine (another SSRI) had higher response rates compared to men. Davidson and Pelton (1986) investigated a sample of depressed individuals with comorbid panic attacks, and found that monoamine oxidase inhibitors (MAOIs) were superior to TCAs in women, while TCAs were superior to MAOIs in men. These differential findings have been related to gender differences in drug absorption, bioavailability, drug distribution, metabolism, and elimination. However, a number of other studies indicate that men and women are equally likely to respond to TCAs, including imipramine (Croughan et al., 1988; Sotsky et al., 1991; Zlotnick et al., 1996) and amitriptyline (Croughan et al., 1988; Paykel et al., 1988). There is a shortage of clinical trials compar-

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ing the response of men and women with major depression to antidepressants other than TCAs.

1.5. Personality A number of personality features have been proposed as vulnerability factors for the development and maintenance of depression. These include neuroticism, introversion, interpersonal dependency, selfcriticism, and perfectionism. All of these features have been reported to be more prominent in depressed individuals than in controls (Hirschfeld et al., 1984; Klein et al., 1988; Franche and Dobson, 1992; Bagby et al., 1994, 1995; Enns and Cox, 1997). In addition, from a cognitive perspective, Beck (1983) proposed that the cognitive styles of autonomy and sociotropy predispose individuals to develop depression. Autonomy, which is related to the constructs of self-criticism and perfectionism, refers to excessive achievement expectations and a strong need for independence. Sociotropy, which is related to interpersonal dependency, refers to a strong need for affiliation and support from others. According to Beck (1983), as a result of socialization, women are more likely to develop sociotropic structures, while men are more likely to develop autonomous structures. This hypothesis was empirically confirmed in a university student sample (Robins et al., 1994). Only very few studies addressed the issue of gender differences in these personality variables in clinically depressed samples. In recovered depressed patients, Hirschfeld et al. (1984) failed to find an effect of gender on interpersonal dependency, and Zlotnick et al. (1996) failed to find gender differences in need for approval and perfectionism as measured by the Dysfunctional Attitude Scale (DAS; Weissman and Beck, 1978). Bothwell and Scott (1997) found acutely depressed men and women to have comparable scores in neuroticism. Perugi et al. (1990) reported that clinically depressed women were significantly more likely to have a ‘depressive temperament’, which includes features of self-criticism and preoccupation with inadequacy and failure. One problem of all studies investigating personality and acute depression, and a usual criticism of such investigations, is the potential influence of depressed mood on personality scores. However, while the finding of abso-

lute change (i.e., the extent to which mean personality scores change or increase / decrease in the context of a depressive episode) of certain personality measures as a function of change in depression is wellestablished, relative stability (i.e., the extent to which the relative differences on personality scores among a group of individuals remain constant in the context of a depressive episode) has been demonstrated for a number of traits including neuroticism and extraversion (Santor et al., 1997), as well as sociotropy and autonomy (Bagby et al., 2001). Thus, there is mounting evidence that personality measures do have stability in the context of changing mood and, therefore do confer vulnerability to depression independent of the state effects of depressed mood (Bagby and Ryder, 2000). In summary, it appears quite possible that the contradictory findings in the presentation of major depression are a result of variation in sampling procedures. Research is needed to elucidate which gender differences can be generalized to a wide range of depressive populations. In the present analyses, we tried to address this issue by investigating gender differences in a sample of outpatients with major depression of varying levels of chronicity and recurrency who are receiving antidepressant treatment. While it may be more difficult to detect gender differences in such a heterogenous population, we believe that potential findings are more powerful as they are not limited to specific depressive subtypes, such as chronic, recurrent, or pure depression.

2. Methods

2.1. Subjects A sample was drawn from a clinical database maintained at the Depression Clinic, Mood and Anxiety Division at the Centre for Addiction and Mental Health (CAMH) (Toronto, Canada) (formerly the Clarke Institute of Psychiatry). The sample comprised 385 outpatients diagnosed with major depression (139 men and 246 women) who were treated with antidepressant medication from 1991 to 1996. All patients recruited into the clinical database were taken from referrals made by psychiatrists and

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general practitioners working in the Greater Metropolitan Toronto Area. Patients were included in the database if they: (1) met the criteria for a primary DSM-III-R or DSM-IV diagnosis of non-psychotic major depression, (2) scored 15 or greater on the 17-item Hamilton Rating Scale for Depression (HRSD; Hamilton, 1967), (3) did not have a concurrent active medical illness (as determined by the referring physician), (4) were medication-free (i.e., of antidepressants) for a minimum of 2 weeks prior to treatment. In addition, patients with comorbid active substance abuse or eating disorders were excluded, while other psychiatric comorbidity was permitted. The subjects were 18–64 years of age.

2.2. Procedure All patients received between 14 and 26 weeks of treatment with antidepressant medication. Patients were assigned non-randomly to one of several different types of antidepressant medication, depending on the clinician’s discretion. Antidepressants included selective serotonin re-uptake inhibitors (SSRIs) (sertraline, fluoxetine, fluvoxamine, paroxetine), tricyclic antidepressants (TCAs) (amitryptiline, anafranil, nortryptiline, desipramine, imipramine, doxepine), selective noradrenaline re-uptake inhibitors (SNRIs) (nore effexor), monoamine oxidase inhibitors (MAOIs) (phenelzine, tranylcypromine), and reversible inhibitors of monoamine oxidase type A (RIMA) (moclobemide). Patients were assessed at initiation of treatment, 8 weeks after initiation of treatment, and at completion of treatment. For these analyses, only data from assessments at treatment initiation and completion were analysed. Treatment was discontinued when patients either (1) responded to treatment and maintained their response for 6 weeks, (2) dropped out of treatment, or (3) 26 weeks after the initial interview. Consistent with standard treatment response protocols, responding was defined as a HRSD score reduction by half and a score of # 7.

2.3. Measures Socio–economic status was assessed according to the Blishen Index, which is designed for the Canadian society and its citizens (Blishen et al., 1987). The Blishen Index ranges from a minimum of 17.81

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to a maximum of 101.74, with a mean of 42.74. A higher Blishen Index indicates a higher socio– econimic status. Prior to the initiation of treatment, patients completed the Beck Depression Inventory (BDI; Beck, 1978) and the Symptom Check-List (SCL-90-R; Derogatis et al., 1992). The BDI is a 21-item self-report inventory and has exhibited strong internal consistency and test–retest reliability (Robins et al., 1994; Zuroff, 1994). The SCL-90-R is a self-report measure of general psychopathology that has been shown to be effective in clinical outcome measurement (Derogatis and Savitz, 1999). Trained clinicians administered the Structured Clinical Interview for DSM-IV, Axis I Disorders (Version 2.0 / Patient Form) (SCID-I / P; First et al., 1995) and the Hamilton Rating Scale for Depression (HRSD; Hamilton, 1967). The HRSD used for the present analyses was based on the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorder Version (SIGHSAD; Williams et al., 1992) and contained 21 original HRSD items as well as eight additional items for atypical symptoms (social withdrawal, weight gain, appetite increase, increased eating, carbohydrate craving, hypersomnia, fatigability, type B diurnal variation). In order to assess personality, we used two measures, the NEO Personality Inventory (NEO-PI; Costa and McCrae, 1985) and the Personal Style Inventory (PSI; Robins et al., 1994). While the NEOPI measures broad band-width personality traits, the PSI is designed to assess more narrow band-width personality traits that have been specifically related to depression. The NEO-PI is based on the Five Factor Model (FFM) of personality, which has been successfully used for investigations of the role of personality in psychopathology (e.g., Trull and Sher, 1994; Bagby et al., 1999). In the FFM, personality is described in terms of five broad domains: neuroticism (N), extraversion (E), openness (O), agreeableness (A), and conscientiousness (C). Accordingly, the NEO-PI measures these five broad personality domains and six facets for each of the domains N, E, and O. Previous studies have demonstrated the reliability and validity of the NEO-PI in clinical and normal samples (Costa and McCrae, 1992; Bagby et al., 1999). The PSI measures personality traits that have been

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specifically hypothesized to be vulnerability factors for depression. This scale has been designed to reduce potential effects of depressed mood on the assessment of trait characteristics and has shown good internal consistency, test–retest stability, and construct validity (Robins et al., 1994; Bagby et al., 1998, 2001). The PSI is composed of two domains, autonomy and sociotropy, as well as three subscales for each domain, including perfectionism / self-criticism (subscale of autonomy) and dependency (subscale of sociotropy). All measures were taken prior to treatment initiation. The HRSD was also administered at the time of treatment completion for the determination of treatment response.

moderate for values between 0.50 and 0.80, and large for values greater than 0.80.

3. Results

3.1. Sample description The ratio between depressed men and women in this sample was 1:1.8. As shown in Table 1, male and female depressed patients did not differ in terms of their age. Men and women were also equally likely to be single (43% vs. 39%), married / living together as if married (38% vs. 34%), or divorced / separated (18% vs. 23%). Male patients had a higher number of years of education and a higher socio– economic status.

2.4. Data analysis For comparison of means, t-tests were computed for parametric data, Mann–Whitney U-tests for ordinal and Pearson’s Chi Square tests for nominal data. Bonferroni corrections were calculated for each scale. Effect sizes were computed for parametric data using Cohen’s d (Cohen, 1977). According to Rosenthal and Rosnow (1984), effect sizes were considered small for values between 0.20 and 0.50,

3.2. Types of symptoms Women reported more vegetative symptoms than men (Table 2). In particular, women reported more somatization (with a moderate effect size), loss of sexual interest, increased eating, and carbohydrate craving. Women also showed a tendency for higher

Table 1 Demographics, course of illness variables, and severity indices in men and women with major depression Men (N 5 139)

Women (N 5 246)

t

df

P

Cohen’s d

Mean

S.D.

Mean

S.D.

Age in years Years of education Socio–economic status (Blishen Index) Age at onset of depression (years) Total number of episodes Duration of current episode (weeks) Number of DSM-IV symptoms a

39.3 15.6 51.0 28.3 2.4 63.2 6.7

11.0 3.3 14.2 12.0 2.1 75.7 1.3

37.7 14.5 46.1 26.0 2.9 52.1 6.9

11.0 2.9 14.8 11.6 2.7 60.2 1.2

1.35 3.55 2.97 1.60 1.59 1.44 1.03

383 373 334 314 271 219 173

0.179 0.000* 0.003* 0.110 0.114 0.151 0.306

0.14 0.37 0.33 0.18 0.19 0.19 0.16

Measures of depression severity BDI total score SCL-90-R Global Severity Index b HRSD total score (17 items) SCID-I / P (A) symptom severity a

27.3 1.4 20.3 23.6

9.8 0.6 3.8 2.1

29.7 1.8 20.8 23.9

8.6 0.6 4.1 1.9

2.38 3.90 1.27 1.32

369 164 383 170

0.018* 0.000* 0.205 0.189

0.25 0.61 0.13 0.20

BDI 5 Beck Depression Inventory; SCL-90-R 5 Symptom Check-List; HRSD 5 Hamilton Rating Scale for Depression; SCID-I / P (A) 5 Structured Clinical Interview for DSM-IV Axis I Disorders, Module A. *P , 0.05. a Data were only available for 71 men and 104 women. b Data were only available for 66 men and 100 women.

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Table 2 Significant mean differences in the symptom profile in men and women with major depression Men (N 5 139)

SCL-90 -R scales Somatization Anxiety Hostility / anger

Women (N 5 246)

Mean

S.D.

Mean

1.07 1.33 0.94

0.67 0.90 0.72

1.53 1.74 1.36

t

df

P

Cohen’s d

3.83 2.89 3.08

164 164 163

0.000* 0.004* 0.002*

0.60 0.45 0.48

S.D.

a

0.81 0.87 1.03

Mean

Mean

U

P

BDI items Worthlessness Loss of sexual interest

1.37 1.18

1.61 1.55

13 574.0 12 897.5

0.015 0.004**

HRSD items Weight gain Appetite increase Increased eating Carbohydrate craving

0.33 0.33 0.36 0.39

0.60 0.55 0.71 0.88

6324.5 6683.0 6339.5 5636.5

0.010 0.043 0.001*** 0.000***

SCID-I (A) items b Weight change Sleep disturbance

2.22 2.60

2.54 2.79

3008.5 3066.5

0.019 0.048

BDI 5 Beck Depression Inventory; SCL-90-R 5 Symptom Check-List; HRSD 5 Hamilton Rating Scale for Depression; SCID-I / P (A) 5 Structured Clinical Interview for DSM-IV Axis I Disorders, Module A. No significant mean differences were found for the SCL-90-R scale phobic anxiety; the BDI items guilt, irritation, sleep disturbance, tiredness, loss of appetite, and weight loss; the HRSD items genital symptoms, loss of appetite, loss of weight, early insomnia, middle insomnia, late insomnia, general somatic symptoms, feelings of guilt, psychic anxiety, somatic anxiety, hypochondriasis, hypersomnia, and fatigue and the SCID-I / P (A) items fatigue and worthlessness / guilt. *P , 0.05 / 4 5 0.0125; **P , 0.05 / 8 5 0.006; ***P , 0.05 / 17 5 0.003. a Data were only available for 66 men and 100 women. b Data were only available for 71 men and 104 women.

weight gain, appetite increase, and sleep disturbance; however, these trends lost statistical significance when the data were subjected to Bonferroni correction. Women experienced a higher level of anxiety and hostility / anger (small effect sizes). They showed a tendency to report more feelings of worthlessness (small effect size), although again this difference lost significance when subjected to Bonferroni correction. In addition to symptoms for which gender differences have been reported in the literature, we found other symptom differences previously unreported. In particular, women had higher scores in the BDI item feelings of unattractiveness (1.53 vs. 1.06; Mann– Whitney U-test 5 11 863, P , 0.05 / 21 5 0.002), and in the SCL-90-R scales interpersonal sensitivity [1.85(60.90) vs. 1.35(60.81); t(164) 5 3.60, P , 0.005 / 9 5 0.006], subjective depression (i.e.,

dysphoric mood) [2.75(60.72) vs. 2.39(60.77); t(164) 5 3.04, P , 0.006], paranoid ideation [1.28(60.94) vs. 0.86(60.84); t(164) 5 2.97, P , 0.006], and psychoticism [1.23(60.70) vs. 0.89(60.58); t(164) 5 3.4, P , 0.006]. Effect sizes were small to moderate.

3.3. Severity of depression There were significant gender differences in selfreported severity of depression as measured by BDI and SCL-90-R with small to moderate effect sizes (Table 1). Women tended to be more severely depressed than men. In contrast, interview-based measures (HRSD and SCID-I / P, Module A) revealed no gender differences in severity of depression. Men

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and women did not differ in the number of depressive symptoms.

3.4. Age of onset, recurrency, and duration of episodes As shown in Table 1, men and women did not differ with regard to course of illness variables, including age of onset of depression, total number of previous major depressive episodes, and duration of the current depressive episode.

3.5. Antidepressant treatment response SSRIs were prescribed to 76 (31%) women and 57 (41%) men; TCAs were prescribed to 118 (48%) women and 50 (36%) men; SNRIs were prescribed to 34 (14%) women and 19 (14%) men. The remaining 13 (10%) men and 18 (7%) women were prescribed either MAOIs or RIMAs. A 2 3 5 Chi Square analysis revealed that depressed men and women were equally likely to receive either type of medication. The dropout rates were 45 (32%) for men and 74 (30%) for women. Men and women were equally likely to withdraw from treatment. Female non-completers were significantly younger than female completers [38.63 vs. 35.5 years; t(244) 5 2.07, P , 0.05], and male non-completers had a lower socio– economic status than male completers [47.1 vs. 52.8;

t(117) 5 2.10, P , 0.05]. There were no differences between completers and non-completers with regard to the other baseline demographic characteristics. Within each group of patients who were prescribed either SSRIs, TCAs, or SNRIs, men and women were equally likely to drop out of treatment. In general, depressed men and women were equally likely to respond to antidepressant medication [55 (59%) of 94 vs. 94 (55%) of 172]. They were also equally likely to respond to SSRIs [21 (62%) of 34 vs. 21 (45%) of 47], TCAs [21 (58%) of 36 vs. 53 (60%) of 89], and SNRIs [7 (54%) of 13 vs. 16 (64%) of 25].

3.6. Personality At the domain level of the FFM, we found significant gender differences only for conscientiousness, with depressed women reporting higher levels than depressed men (Table 3). At the facet level, women scored higher on the E facet warmth [19.4(65.4) vs. 17.0(65.7); t(287) 5 3.56; P , 0.05 / 18 5 0.003; Cohen’s d 5 0.42] and on the O facet feelings [23.1(64.3) vs. 21.1(64.7); t(287) 5 3.56; P , 0.003; Cohen’s d 5 0.43]. Effect sizes for these variables were small. Depressed women reported higher levels of sociotropy than men, but did not differ in autonomy or the subscales of the PSI (Table 3). Before Bonferroni correction (P , 0.05 / 6 5 0.008), women scored

Table 3 Personality profile in men and women with major depression Men (N 5 104)

NEO-PI dimensions Neuroticism Extraversion Openness Agreeableness Conscientiousness PSI dimensions a Autonomy Sociotropy

Women (N 5 185)

t

df

P

Cohen’s d

Mean

S.D.

Mean

S.D.

121.9 84.3 114.7 43.7 37.5

21.9 21.5 21.6 8.4 11.2

126.5 87.8 117.1 45.9 41.9

23.1 23.0 19.1 9.2 10.3

1.66 1.25 0.94 1.94 3.37

287 287 193 287 287

0.099 0.214 0.350 0.053 0.001*

0.20 0.15 0.14 0.23 0.40

93.5 98.1

15.9 16.6

92.5 104.2

18.0 16.3

0.43 2.55

194 194

0.665 0.012**

0.06 0.37

NEO-PI 5 NEO Personality Inventory; PSI 5 Personality Style Inventory. *P , 0.05 / 5 5 0.01; **P , 0.05 / 2 5 0.025. a Data were only available for 79 men and 117 women.

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higher on the sociotropy subscales concern what others think [30.4(66.4) vs. 28.3(66.8); t(194) 5 2.28; P 5 0.024; Cohen’s d 5 0.33] and pleasing others [45.1(67.8) vs. 42.4(67.5); t(194) 5 2.38; P 5 0.018; Cohen’s d 5 0.34], as well as on the autonomy subscale perfectionism / self-criticism [19.0(63.2) vs. 17.8(63.6); t(165) 5 2.29; P 5 0.023; Cohen’s d 5 0.36]. Effect sizes for these variables were small.

4. Discussion The ratio of men and women in the present analyses (1:1.8) is consistent with the female preponderance in major depression reported in the literature (Weissman and Klerman, 1977; Kessler et al., 1993; Weissman et al., 1993; Oldehinkel et al., 1999). However, since data for the present analyses were collected in a treatment facility, one cannot rule out that this ratio is influenced by a potential gender difference in the willingness to seek treatment. The present analyses investigated gender differences in clinical characteristics of depression, response to antidepressant medication, and personality in outpatients with major depression. In contrast to other studies, the present sample was not restricted to specific unipolar depressive subtypes, such as chronic, recurrent, or pure depression. As a result, findings of gender differences in these analyses may be generalized to a wide range of depressive populations. Overall, men and women in the present sample showed some gender differences in symptoms and self-reported severity of depression, but these differences did not appear to translate into gender differences in response to antidepressants. As in a number of previous studies, women reported more vegetative symptoms than men, including increased eating, carbohydrate craving, as well as loss of sexual interest. There was a trend for higher levels of weight gain in women. Women also reported higher levels of anxiety and anger. Results from these analyses add to the growing body of evidence that depression in women may be complicated by vegetative symptoms and anxiety, which are likely to be distressing for the depressed individual. On the other hand, depressed men in this and previous clinical studies do not appear to preponder-

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ate in any of the symptoms relative to depressed women. This could contribute to explanations of the gender difference in prevalence rates. Indeed, Silverstein (1999) found that women in the general population exhibit twice the prevalence of major depression associated with somatic symptoms and anxiety as men, while the prevalence of pure depression (i.e., with less than three somatic symptoms) was very similar for men and women. As in the studies of Frank et al. (1988) and Kornstein et al. (2000a) in samples of outpatients with recurrent or chronic depression, in this sample women scored significantly higher on self-report measures of depression severity, while this difference was absent in clinical interviews. In line with the absence of a gender difference in clinician-rated depression severity, men and women in our analyses did not differ in the number of depressive symptoms, as was found in a sample of individuals with dysphoric mood (Angst and Dobler-Mikola, 1984). The tendency of women to self-report greater severity of depression is consistent with the notion that women tend to focus on themselves and their mood when they are in a depressed state, to a greater extent than do men (Butler and Nolen-Hoeksema, 1994). Accordingly, Nolen-Hoeksema (1987, 1990) proposed that due to gender–role socialization, women are more likely to ruminiate to depressed mood, whereas men tend to distract themselves (response styles theory). A ruminative response style will be likely to increase the awareness of one’s mood and somatic symptoms, and as such will result in higher scores on self-report measures of depression. No gender differences were evident in the course of the illness features, such as age of onset, number of previous episodes, and duration of current episode. Along with previous clinical studies (Frank et al., 1988; Thase et al., 1994; Kornstein et al., 1995, 2000a; Simpson et al., 1997), our analyses indicate that gender differences in the chronicity and recurrency of depression found in community studies (Amenson and Lewinsohn, 1981; Sargeant et al., 1990; Ernst and Angst, 1992; Bracke, 1998) may not be generalized to clinical in- and outpatient populations. Response style theory (Nolen-Hoeksema, 1987, 1990) proposes that women’s ruminative response to depressed mood both amplifies and prolongs their episodes of depression. However, even

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though in our sample women self-reported higher severity of depression, they did not report longer duration of episodes. It appears that while the ruminative response style of women in clinical populations exacerbates their mood disturbance, it does not necessarily prolong their depressive episodes. Despite the differences in symptoms and selfreported severity, men and women did not differ in their response to antidepressant medication in general, nor to SSRIs, MAOIs, and TCAs in particular. This contrasts the finding that females respond more favourable to fluoxetine compared to men (Haykal and Akiskal, 1999). Only very few previous studies investigated gender differences in response to antidepressants other than TCAs. In contrast to our finding, women were reported to respond more poorly to imipramine in samples with recurrent depression (Frank et al., 1988) and chronic depression (Kornstein et al., 2000b), and to TCAs in general in a depressed sample with comorbid panic attacks (Davidson and Pelton, 1986). In the present analyses, we did not specifically investigate response to imipramine, but response to a group of various tricyclic agents, which might partly explain these inconsistencies. We also did not replicate findings that women respond more favourably than men to MAOIs and SSRIs reported in the same studies (Davidson and Pelton, 1986; Kornstein et al., 2000b), nor the finding of a better treatment response to the SSRI fluoxetine in women with dysthymia (Haykal and Akiskal, 1999). Our results suggest that women’s poorer response to TCAs and men’s poorer response to MAOIs and SSRIs may be restricted to specific depressive subtypes, and may not generalize to other groups of patients with unipolar depression. Only very few differences were evident in the personality profiles of depressed men and women. There was a lack of significant differences in almost all of the domains and facets of the FFM. Women did score higher than men on conscientiousness and on the E facet warmth and the O facet feelings; however, effect sizes were small. There are no previous studies on depressed populations that investigate gender differences in the personality domains conceptualized in the FFM. Feingold (1994) conducted an exhaustive meta-analysis of gender differences in personality in the normal population. Across various

personality inventories, age groups, education levels, and cultures, women were higher than men in extraversion, anxiety (facet of N), trust (facet of A), and tender-mindedness (facet of A), while men were more assertive than women (facet of E). Men and women in the present sample did not differ in extraversion, anxiety, assertiveness, or in the domain of agreeableness, which contains trust and tendermindedness. This suggests that depressed men and women in an outpatient setting are more similar than are men and women in normal populations. A possible explanation for this lack of gender differences is the assumption of a certain personality type that predisposes individuals to develop clinical depression, independent of gender (Blatt et al., 1982; Phillips et al., 1990; Enns and Cox, 1997). Women showed higher levels of sociotropy than men, indicating that they tend to define their selfworth through contact with and approval from others, to a greater extent than do men. This finding is consistent with Beck’s (1983) proposal that women are more likely to develop sociotropic personality structures. We did not confirm Beck’s notion that men are more prone to an autonomous cognitive style than women. While gender differences in sociotropy and autonomy as proposed by Beck have been reported for a university student sample (Robins et al., 1994), our analyses are the first to investigate this hypothesis in clinically depressed individuals. Results only partially confirm Beck’s proposal of gender differences in cognitive styles in outpatients with major depression.

5. Conclusion These analyses tried to elucidate which gender differences in unipolar depression previously reported for different, and partly quite narrowly defined, depressive populations can be generalized to outpatients with major depression of varying levels of chronicity and recurrency who are receiving antidepressant treatment. The preponderance of somatic symptoms and anger, along with a higher self-reported severity of illness in women appears to constitute a robust gender difference in major depression. On the other hand, previously reported gender differences in the course of depression were not

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found in the present sample. Gender differences in the psychopathology of depression did not translate into differences in response to antidepressants. The personality profile of depressed men and women appears to be more similar than in the average population, suggesting that depression may be linked to a certain personality type that makes individuals vulnerable to become depressed, independent of gender. One limitation of the present analyses is that findings are not generalizable to inpatient or community samples. Another limitation is that participation depended on the willingness of patients to accept treatment. If we assume that women are more willing to seek treatment than men, some of the gender differences may be accounted for by gender differences in treatment seeking behaviour. Findings may further be compromised by our exclusion criteria necessary to ensure a study group suitable for a clinical treatment trial. For example, exclusion of patients with comorbid substance abuse or eating disorders may have influenced our findings of gender differences, as there are important sex differences in the prevalence of these comorbidities (Woodside and Kennedy, 1995; Frank, 2000). In summary, despite several psychopathological differences in the expression of depression in women, within the limitations of our study, we could not demonstrate treatment response or course differences.

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