Self-reported premenstrual exacerbation of depressive symptoms in patients seeking treatment for major depression.

BACKGROUND: Very little research has examined the frequency with which women with major depressive disorder experience premenstrual exacerbation (PME) of depression or the characteristics of those who report such worsening. The NIMH Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study provides a unique opportunity to evaluate PME in depressed women seeking treatment in primary care or psychiatric settings. METHOD: This report presents data from the first 1500 participants enrolled in the STAR*D study. Premenopausal women with major depressive disorder were asked if they experienced a worsening of their depressive symptoms 5-10 days prior to menses. Those reporting PME were compared with those reporting no PME with regard to sociodemographic characteristics, course of illness features, symptom presentation, general medical co-morbidity, functional impairment, and quality of life. RESULTS: Of 433 premenopausal women not taking oral contraceptives, 64% reported a premenstrual worsening of their depression. Women who reported PME had a longer duration of their current major depressive episode [30.7 (S.D. = 73.7) months versus 13.5 (S.D. = 13.2) months; p=0.001], as well as greater general medical co-morbidity. Women reporting PME were also more likely to endorse symptoms of leaden paralysis, somatic complaints, gastrointestinal complaints, and psychomotor slowing, and were less likely to endorse blunted mood reactivity. CONCLUSIONS: PME is endorsed by the majority of premenopausal women with major depressive disorder and appears to be associated with a longer duration of depressive episode. PME is a common and important clinical issue deserving of further attention in both research and practice.

The evaluation and management of depression in women across the life span.

Depression is more common in women than in men, particularly during the childbearing years. Women may present with different depressive symptoms than men and may respond differently to antidepressant treatment. In addition, depression in women can surface in association with specific points in the reproductive cycle, such as during the premenstrual period, during pregnancy and the postpartum period, and during the perimenopausal years. Antidepressant medications may be used effectively at all stages in a woman's life. In the case of premenstrual dysphoric disorder, serotonergic agents have demonstrated efficacy in both full-cycle and luteal-phase dosing strategies. For depressed women who are pregnant or breastfeeding, the limited safety data available on antidepressants suggest minimal danger to the fetus or infant, and the risks and benefits to both mother and child must be weighed against the risks of untreated illness. Treatment of depression in middle-aged and elderly women should take into account the possible influence of both menopausal status and hormone replacement therapy on antidepressant response. This article will focus on special considerations in the evaluation and management of depression in women across the life span.

Clinical features of treatment-resistant depression.

As many as 30% to 40% of patients with major depressive disorder are unresponsive to a trial of antidepressant medication. Many patients labeled with treatment-resistant depression actually have pseudoresistance, in that they have been inadequately treated or are misdiagnosed. Others may have unrecognized comorbid psychiatric or general medical conditions that contribute to treatment resistance. Variables such as gender, family history, age at onset, severity, and chronicity have also been evaluated as possible risk factors for treatment-resistant depression. This article reviews the current literature regarding the clinical characteristics of treatment-resistant depression, with particular attention to the relevance of these factors for clinical decision making.

Sertraline versus imipramine to prevent relapse in chronic depression.

BACKGROUND: Chronic depressions are common, disabling and under-treated, and long-term treatment is little studied. We report the continuation phase results from a long-term treatment study. METHODS: After 12 weeks of acute phase treatment in a double-blind, randomized, parallel-group, multi-center trial of sertraline or imipramine, patients with chronic depression (> or = 2 years in major depression, or major depression superimposed on dysthymia) continued study drug for 16 weeks. Initially, 635 patients were randomized to sertraline or imipramine in a 2:1 ratio. Nonresponders after 12 weeks entered a 12-week double-blind crossover trial of the alternate medication. Entry into continuation treatment required at least a satisfactory response (partial remission) to initial or crossover treatment. RESULTS: Of 239 acute or crossover responders to sertraline, 60% entered continuation in full remission and 40% with a partial remission. These proportions were identical for imipramine patients (n = 147). For both drug groups, over two-thirds of those entering in full remission retained it. For those entering in partial remission, over 40% achieved full remission. Patients requiring crossover treatment were less likely to maintain or improve their response during continuation treatment. The two drugs did not differ significantly in response distribution, drop out rates or discontinuation due to side effects during continuation treatment. LIMITATIONS: The absence of a placebo group constrains interpretation of our results, but chronic depressions have low placebo response rates. CONCLUSIONS: Most chronic depression patients who remit with 12 weeks of sertraline or imipramine treatment maintain remission during 16 weeks of continuation treatment. Most patients with a satisfactory therapeutic response (partial remission) after 12 weeks of treatment maintain it or further improve. Patients treated with imipramine experienced more side effects, but both drugs were well tolerated.

Comparison of DSM-III-R chronic major depression and major depression superimposed on dysthymia (double depression): validity of the distinction.

The nosology of chronic depression has become increasingly complex since the publication of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R; American Psychiatric Association, 1987), but there are few data available to evaluate the validity of the distinctions between the subtypes of chronic depression. The validity of the distinction between DSM-III-R chronic major depression (CMD) and major depression superimposed on dysthymia (double depression, DD) was examined. Participants were 635 patients with chronic depression in a 12-week trial of antidepressant medications. Patients with CMD, DD, and a 3rd group with a chronic major depressive episode superimposed on dysthymia (DD/CMD) were compared on demographic and clinical characteristics, family history, and response to treatment. Few differences were evident, although the depression of patients with DD/CMD tended to be more severe.

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

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.

Enhancing pharmacologic effects in the treatment of depression in women.

The prevalence of depressive disorders in women is twice that in men. This gender difference emerges around the time of puberty and persists through the childbearing years. Reproductive events and psychosocial factors are important influences on depression in women. Women often present with atypical depressive symptoms and comorbid disorders that can complicate both diagnosis and treatment. Sex differences in pharmacokinetics have been noted, as well as differences in antidepressant treatment response. While sleep disturbances, sexual dysfunction, and weight gain may be part of the constellation of depressive symptoms, they are also important considerations in selecting a treatment option for depressed women.

Gender differences in chronic major and double depression.

BACKGROUND: While the sex difference in prevalence rates of unipolar depression is well established, few studies have examined gender differences in clinical features of depression. Even less is known about gender differences in chronic forms of depression. METHODS: 235 male and 400 female outpatients with DSM-III-R chronic major depression or double depression (i.e., major depression superimposed on dysthymia) were administered an extensive battery of clinician-rated and self-report measures. RESULTS: Women were less likely to be married and had a younger age at onset and greater family history of affective disorder compared to men. Symptom profile was similar in men and women, with the exception of more sleep changes, psychomotor retardation and anxiety/somatization in women. Women reported greater severity of illness and were more likely to have received previous treatment for depression with medications and/or psychotherapy. Greater functional impairment was noted by women in the area of marital adjustment, while men showed more work impairment. LIMITATIONS: Since our population consisted of patients enrolling in a clinical trial, study exclusion criteria may have affected gender-related differences found. CONCLUSIONS: Chronicity of depression appears to affect women more seriously than men, as manifested by an earlier age of onset, greater family history of affective disorders, greater symptom reporting, poorer social adjustment and poorer quality of life. These findings represent the largest study to date of gender differences in a population with chronic depressive conditions.

Lost human capital from early-onset chronic depression.

OBJECTIVE: Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. METHOD: The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. RESULTS: Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. CONCLUSIONS: Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

Maintenance phase efficacy of sertraline for chronic depression: a randomized controlled trial.

CONTEXT: The chronic form of major depression is associated with a high rate of prevalence and disability, but no controlled research has examined the impact of long-term treatment on the course and burden of illness. OBJECTIVE: To determine if maintenance therapy with sertraline hydrochloride can effectively prevent recurrence of depression in the high-risk group of patients experiencing chronic major depression or major depression with antecedent dysthymic disorder ("double depression"). DESIGN: A 76-week randomized, double-blind, parallel-group study, conducted from September 1993 to November 1996. SETTING: Outpatient psychiatric clinics at 10 academic medical centers and 2 clinical research centers. INTERVENTION: Maintenance treatment with either sertraline hydrochloride (n = 77) in flexible doses up to 200 mg or placebo (n = 84). PATIENTS: A total of 161 outpatients with chronic major or double depression who responded to sertraline in a 12-week, double-blind, acute-phase treatment trial and continued to have a satisfactory therapeutic response during a subsequent 4-month continuation phase. MAIN OUTCOME MEASURE: Time to recurrence of major depression. RESULTS: Sertraline afforded significantly greater prophylaxis against recurrence than did placebo (5 [6%] of 77 in the sertraline group vs 19 [23%] of 84 in the placebo group; P = .002 for the log-rank test of time-to-recurrence distributions). Clinically significant depressive symptoms reemerged in 20 (26%) of 77 patients treated with sertraline vs 42 (50%) of 84 patients who received placebo (P = .001). With use of a Cox proportional hazards model, patients receiving placebo were 4.07 times more likely (95% CI, 1.51-10.95; P = .005) to experience a depression recurrence, after adjustment for study site, type of depression, and randomization strata. CONCLUSIONS: Maintenance therapy with sertraline is well tolerated and has significant efficacy in preventing recurrence or reemergence of depression in chronically depressed patients.

The treatment of chronic depression, part 2: a double-blind, randomized trial of sertraline and imipramine.

BACKGROUND: Chronic depression appears to be a common, frequently disabling illness that is often inadequately treated. Unlike episodic depressions with shorter illness duration, neither acute nor long-term treatment approaches for chronic depression have been well studied. METHOD: 635 outpatients at 12 sites who met DSM-III-R criteria for chronic major depression or double depression were randomly assigned to 12 weeks of double-blind treatment with either sertraline (in daily doses of 50-200 mg) or imipramine (in daily doses of 50-300 mg). Efficacy and safety were assessed either weekly or every 2 weeks during the 12 weeks of acute treatment. RESULTS: Despite high rates of chronicity (mean duration of major depression = 8.9+/-9.1 years; mean duration of dysthymia = 23+/-13 years) and high rates of comorbidity, 52% of patients achieved a satisfactory therapeutic response to sertraline or imipramine (by a conservative, intent-to-treat analysis). Approximately 21% of the patients who had achieved a therapeutic response at week 12 had not done so at week 8, confirming the longer time to response in depressions with high chronicity. Patients treated with sertraline reported significantly fewer adverse events and were significantly less likely to discontinue treatment due to side effects than imipramine-treated patients (6.3% vs. 12.0%). CONCLUSION: These results indicate that patients suffering from depression with high chronicity can achieve a good therapeutic response to acute treatment with either sertraline or imipramine, although sertraline is better tolerated.

The treatment of chronic depression, part 3: psychosocial functioning before and after treatment with sertraline or imipramine.

BACKGROUND: Previous research has suggested that depressed patients, and particularly chronically depressed patients, have significant impairments in many areas of their lives. While previous studies suggested that these "psychosocial" impairments improve following pharmacologic treatment, no large scale definitive study using multiple measures of psychosocial functioning has been reported. METHOD: We assessed multiple domains of psychosocial functioning using interviewer-rated and self-report measures within the context of a 12-week acute treatment trial of sertraline and imipramine for patients with chronic depression (double depression and chronic major depression). We also compared the psychosocial functioning data of this sample before and after treatment with normative data available from published community samples. RESULTS: Chronically depressed patients manifested severe impairments in psychosocial functioning at baseline. After treatment with sertraline or imipramine, psychosocial functioning improved significantly. Significant improvements appeared relatively early in treatment (week 4). Despite these highly significant improvements in functioning during acute treatment, the study sample as a whole did not achieve levels of psychosocial functioning comparable to a comparator nondepressed community sample. However, patients who reached full symptomatic response (remission) during acute treatment did have levels of psychosocial functioning in most areas at endpoint that approached or equaled those of community samples. CONCLUSION: These results indicate that successful antidepressant treatment with sertraline or imipramine can alleviate the severe psychosocial impairments found in chronic depression.

Women in medicine: shaping the future.

The dramatic increase in the number of women in medicine presents some new challenges to an old institution. This article provides an overview of current trends and future directions as greater numbers of women are entering medicine. The first section describes women's particular approach to medicine, including their motivations for pursuing medicine as a career, their specialty choices and practice patterns, their attitudes about patient care and doctor-patient relationships, and their advocacy for women's health issues. The second section documents women's negative experiences in medicine, such as higher stress levels than men, gender discrimination, sexual harassment, role strain, and a paucity of mentors and role models. In the final section, the authors suggest how medicine as an institution can change to better accommodate women.

Menstrual migraines: etiology, treatment, and relationship to premenstrual syndrome.

Migraine headache is a common condition in women and frequently occurs in relation to the menstrual cycle. This article reviews the neuroendocrine etiology of menstrual migraine, its possible relationship to premenstrual syndrome, and recent developments in treatment strategies for these often refractory headaches.

Gender differences in depression: implications for treatment.

The study of gender differences in psychiatric disorders has received increasing attention in recent years. Depression has emerged as an important area of focus, as epidemiologic data have consistently shown that depression is twice as common in women as in men. In addition to this difference in prevalence, there may be gender differences in presentation, course of illness, and treatment response to both medications and psychotherapy. This article reviews current knowledge of gender differences in depression and presents recommendations for gender-specific assessment and treatment of depression.

Differential diagnosis of chronic depressive disorders.

This article has traced the development of the diagnostic nomenclature for the chronic affective disorders during the past four decades. Much has been accomplished. In fact, our current differential diagnostic capabilities have surpassed our knowledge of how to treat the chronic depressions. It is hoped that in the next decade there will be notable increases in the treatment efficacy literature of the chronic mild depressions. Next, we suggest that practitioners assist academic investigators in determining the best way to treat the chronic depressions. To realize this goal, clinicians must begin to view themselves as part-time researchers. Several technological procedures have been described to facilitate this undertaking. We suggest that the assumption of such a research practitioner role will, in the long run, improve the quality of patient care.

Gender differences in presentation of chronic major depression.

The authors examine gender differences in presentation of illness in 96 males and 198 females with DSM-III-R chronic major depression (i.e., major depression of at least 2 years' duration). Women were found to have increased severity of illness as measured by Hamilton Rating Scale for Depression (HAM-D), Beck Depression Inventory (BDI), and Clinical Global impressions (CGI) scores. Symptom comparisons revealed that women experience more psychomotor retardation than men. Women reported increased functional impairment on the Social Adjustment Scale-Self-Report (SAS-SR), particularly in the areas of marital and family adjustment. Men were more likely to have a history of alcohol and substance abuse/dependence. These findings represent the first systematic study of gender differences in a chronic depressive population.