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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. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional data show that generalised anxiety disorder (GAD) is a chronic condition with episodes lasting much longer than the six-month minimum required by DSM-III-R and DSM-IV. Although GAD is chronic, little is known about factors influencing illness duration.Aims: To investigate variables that influence the clinical course of GAD.Method: A total of 167 patients with GAD participated in the Harvard-Brown Anxiety Research Program. Patients were assessed at intake and re-examined at six- to twelve-month intervals for five years. Kaplan-Meier curves were constructed to assess the likelihood of remission. Regression analysis was used to investigate factors predicting full or partial remission.Results: The rate of remission was 0.38 after five years. Diminished likelihood of remission was associated with low overall life satisfaction, poor spousal or family relationships, a concurrent cluster B or C personality disorder and a low global assessment score.Conclusions: Full or partial remissions were less likely to occur in patients with poor relationships and personality disorders. These patients should be given more intensive and possibly multi-modal therapy. [ABSTRACT FROM AUTHOR]

Objective: Panic disorder with or without agoraphobia has a chronic relapsing course. Factors associated with poor outcome include early onset of illness and phobic avoidance. Several, but not all, authors have found a worse clinical course for women. Using observational, longitudinal data from the Harvard/Brown Anxiety Disorders Research Program, the authors analyzed remission and symptom recurrence rates in panic patients with respect to sex.Method: Male and female patients (N = 412) in an episode of panic with or without agoraphobia were assessed by structured interview and prospectively followed for up to 5 years. Data on remission, symptom recurrence, and comorbid psychiatric conditions for each sex were compared.Results: There were no significant differences between men and women in panic symptoms or level of severity at baseline. Women were more likely to have panic with agoraphobia (85% versus 75%), while men were more likely to have uncomplicated panic (25% versus 15%). The rates of remission for panic with or without agoraphobia at 5 years were equivalent in men and women (39%). Of the subjects who achieved remission, 25% of the women and 15% of the men reexperienced symptoms by 6 months. Recurrence of panic symptoms continued to be higher in women (82%) than men (51%) during the follow-up period and was not influenced by concurrent agoraphobia.Conclusions: This study extends previous findings by showing that not only are women more likely to have panic with concurrent agoraphobia, but they are more likely than men to suffer a recurrence of panic symptoms after remission of panic. [ABSTRACT FROM AUTHOR]

Background: The diagnostic category of generalised anxiety disorder (GAD) was originally intended to describe residual anxiety states. Over the years clinical criteria have been refined in an attempt to describe a unique diagnostic entity. Given these changes, little is known about the clinical course of this newly defined disorder. This study investigates the longitudinal course, including remission and relapse rates, for patients with DSM-III-R defined GAD.Method: Analysis of the 164 patients with GAD participating in the Harvard Anxiety Research Program. Patients were assessed with a structured clinical interview at intake and re-examined at six month intervals for two years and then annually for one to two years. Psychiatric Status Ratings were assigned at each interview point. Kaplan-Meier curves were constructed to assess likelihood of remission.Results: Comorbidity was high, with panic disorder and social phobia as the most frequently found comorbid disorders. The likelihood of remission was 0.15 after one year and 0.25 after two years. The probability of becoming asymptomatic from all psychiatric symptoms was only 0.08.Conclusions: This prospective study confirms the chronicity associated with GAD and extends this finding to define the one and two year remission rates for the disorder. Likelihood of remission for GAD and any other comorbid condition after one year was half the annual remission rate for GAD alone. [ABSTRACT FROM AUTHOR]

Objective: Postpartum depressive disorders lead to maternal disability and disturbed mother-infant relationships, but information regarding the rates of major depressive disorder in minority women is noticeably lacking. The goal of this study was to determine whether the risk factors for and rate of postpartum major depressive disorder in a predominantly African American and Hispanic clinic population would be similar to those reported for Caucasian women., Method: Investigators systematically screened all women scheduled for their first postpartum visit on selected days at four publicly funded inner-city community maternal health clinics in Dallas County (N=802). A multistage screening process included the Edinburgh Postnatal Depression Scale, the Inventory of Depressive Symptomatology, and the Structured Clinical Interview for DSM-IV for a maximum of three assessments during the initial 3-5-week postpartum period., Results: The estimated rate of major depressive disorder during the postpartum period among women in this setting was between 6.5% and 8.5%. Only 50% of the depressed women reported onset following birth. Bottle-feeding and not living with one's spouse or significant other were associated with depression at the first evaluation; persistent depressive symptoms were linked with the presence of other young children at home. Greater severity of depressive symptoms at first contact predicted major depressive disorder several weeks later., Conclusions: Rates of postpartum depression among Latina and African American postpartum women are similar to epidemiologic rates for Caucasian postpartum and nonpostpartum women. As previously shown for Caucasian women, major depressive disorder in many Latina and African American postpartum women begins before delivery, revealing the need to screen pregnant women for depression.

Objective: Social phobia is a chronic disorder with a higher prevalence among women than men. Data from an eight-year longitudinal study were analyzed to investigate the course of social phobia and to explore potential sex differences in the course and characteristics of the illness., Methods: Data were analyzed from the Harvard/Brown Anxiety Research Program, a naturalistic, observational study begun in 1989 in which patients with social phobia are assessed every six to 12 months. Treatment was observed but not prescribed by the program personnel. Data on comorbidity, remission, and health-related quality of life were collected for 176 patients with social phobia., Results: Only 38 percent of women and 32 percent of men experienced a complete remission during the eight-year study period, a difference that was not significant. A larger proportion of women than men had the generalized form of social phobia, although the difference was not significant. Women were more likely to have concurrent agoraphobia, and men had a higher rate of comorbid substance use disorders. Social phobia had a more chronic course among women who had low Global Assessment of Functioning scores and a history of suicide attempts at baseline than among men who had these characteristics. Health-related quality of life was similar for both men and women, except that women were slightly but significantly more impaired in household functioning., Conclusions: The chronicity of social phobia was striking for both men and women. Although remission rates did not differ significantly between men and women, clinicians should be alert to the fact that women with poor baseline functioning and a history of suicide attempts have the greatest chronicity of illness.

Women have a higher prevalence of GAD than do men. This ratio holds true in most clinical and general-population samples. Some variations exist, with evidence to suggest the strong impact of environment and life events. Women are sensitive to lifetime adversity and exacerbation of symptoms in conjunction with their menstrual cycle. Comorbidity is a crucial diagnostic factor when treating anyone with GAD, especially women. Most notably, high comorbidity with other anxiety disorders, MDD and alcohol-abuse disorder occurs for women. Overall, although the prevalence of women with GAD is greater than that of men with GAD, the course of illness and prognosis are not qualitatively different. Across varied methodology, data suggest gender-related differences in the metabolism and potentially in the effects and side effects of the various benzodiazepines and antidepressant psychopharmacologic treatments of GAD. Additional research is needed to better understand these differences.

Background: The objective of this study was to evaluate the pretreatment psychosocial functioning of women with premenstrual dysphoric disorder (PMDD) and the effect of sertraline treatment on psychosocial functioning in these patients., Method: Two hundred forty-three women recruited from 12 university-affiliated sites and meeting DSM-IV criteria for PMDD completed 1 cycle of single-blind placebo and were randomly assigned to flexible dose sertraline or placebo for 3 cycles. Psychosocial functioning was assessed by the Daily Record of Severity of Problems (DRSP), the Social Adjustment Scale (SAS), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q)., Results: SAS scores during the follicular phase were similar to SAS scores of community norms, whereas the pretreatment SAS and Q-LES-Q scores during the luteal phase were similar to scores of women with depressive disorders. Sertraline was significantly more effective than placebo in improving psychosocial functioning as measured by the SAS, the Q-LES-Q, and the 3 DRSP items of impaired productivity, interference with social activities, and interference with relationships with others. Improvement in psychosocial functioning assessed by SAS and Q-LES-Q correlated with improvement in symptomatology assessed by the Clinical Global Impressions-Improvement (CGI-I) scale and the Hamilton Rating Scale for Depression (HAM-D). Remitters (CGI-I score of 1) were more likely to function better at baseline and showed larger improvements in functioning and quality of life with treatment compared with nonremitters., Conclusion: Sertraline was superior to placebo in improving psychosocial functioning in women with PMDD as reflected by SAS, Q-LES-Q, and DRSP measures. Functional improvement correlated with improvement in premenstrual symptomatology and was apparent by the second cycle of treatment. Comparison of pretreatment SAS scores in women with PMDD with the scores of other populations of women documents the degree of luteal phase functional impairment in women with PMDD and a relative absence of follicular phase impairment.

Background: Women are overrepresented in samples of patients with rapid cycling bipolar disorder (RCBD). To explore whether menstrually related mood changes might account for this gender difference, we studied the relationship between menstrual cycle phase and mood in a sample of premenopausal women with rapid cycling bipolar disorder (RCBD)., Methods: Twenty-five women with RCBD completed daily self-rating forms indicating their mood and days of menstruation for a minimum of three months. The data were analyzed for each individual and for the group as a whole, categorically (depression, euthymia, and hypomania) and ordinally (0-100, with 0 being "most depressed ever felt" and 100 being "most manic"), with and without normalization of the menstrual cycle to a 28-day cycle., Results: None of the group analyses showed a significant effect of menstrual cycle on mood. Although some women did exhibit significant relationships between menstrual cycle phase and categorical mood state, there was no consistent pattern to the relationship., Conclusions: There was no systematic relationship between menstrual cycle and mood in a sample of women with RCBD.

Women who suffer from severe dysphoric premenstrual complaints can now be accurately diagnosed. A diagnosis of premenstrual dysphoric disorder is best made by ruling out other psychiatric and general medical conditions and by collecting daily ratings of symptom expression across the menstrual cycle. Recent treatment findings support the use of (1) antidepressants that block the serotonin transporter, and (2) the benzodiazepine anxiolytic alprazolam. Medication administered only during the luteal phase of the cycle will result in substantial relief for patients suffering from severe premenstrual dysphoric disorder.

Background: Abnormal alpha 2-adrenergic receptor (AR) function is implicated in anxiety and depressive disorders. Premenstrual dysphoric disorder (PMDD) is characterized by anxiety and depressive symptoms, which may be associated with changes in alpha 2AR function. Previous studies on alpha 2AR function during phases of the menstrual cycle in controls and PMDD patients are inconsistent., Methods: alpha 2AR function was examined in 16 PMDD patients and 15 controls during the follicular phase, and in 10 PMDD patients during late luteal phase. Antagonist-measured maximum binding capacity, agonist-measured receptor density in high- and low-conformational states, and agonist affinity to both states were measured. Coupling efficiency to Gi protein was estimated., Results: There were no significant differences in coupling efficiency. PMDD patients had significantly low antagonist affinity; there were no differences in other binding parameters. There were no changes in alpha 2AR binding parameters between phases of menstrual cycle in PMDD women. alpha 2AR density and symptom severity were inversely related during the follicular phase in controls and patients. During luteal phase, alpha 2AR density correlated positively with symptom severity in patients. High follicular alpha 2AR density predicted more severe luteal symptoms in PMDD patients., Conclusions: These findings are discussed in view of the molecular biology of alpha 2AR, and their role in PMDD, anxiety, and depressive disorders.

Abnormal beta2-adrenergic receptor coupling to Gs protein is implicated in depressive disorders. Steroid hormones and antidepressants modulate beta-adrenergic receptor coupling, which may relate to the therapeutic efficacy of antidepressants. We examined beta2-adrenergic receptors in 18 patients with premenstrual dysphoric disorder (PMDD), in 15 control subjects during the follicular phase and in 12 patients during late luteal phase. Antagonist-measured receptor density, agonist-measured receptor density in the high- and low-conformational states and agonist affinity to both states were measured. Coupling indices to Gs protein were determined from agonist-displacement experiments. Follicular beta2-adrenergic receptor density was higher in patients than in control subjects, with a trend for higher receptor density in the high-conformational state. The phase of menstrual cycle had no effect on beta2-adrenergic receptor regulation in PMDD. Exploratory correlations showed that the K(L)/K(H) ratio was related to anxiety ratings in control subjects and %R(H) was correlated with symptom severity in patients. In patients, follicular beta2-adrenergic receptor binding measures were correlated with luteal symptom severity. These findings suggest abnormal beta2-adrenergic receptor regulation in PMDD. Further exploration of the role of beta-adrenergic receptor kinase, sex steroid hormones and antidepressants on beta-adrenergic receptor regulation in PMDD is warranted.

Lithium is used as a primary treatment or augmentation therapy for several psychiatric conditions, such as bipolar depression, mania and unipolar depression. For many patients with bipolar disorder, it is the most effective mood stabiliser.More than half of the patients maintained on lithium are women, and many are of reproductive age. An unknown proportion of women who are receiving lithium maintenance therapy become pregnant, posing numerous clinical issues for the obstetrician, psychiatrist and patient. The specific problems associated with lithium exposure vary during different stages of gestation. The risk of the serious heart defect, Ebstein's anomaly, exists if the drug is taken during weeks 2 to 6 post-conception; risks of fetal/neonatal complications occur if lithium is taken during the second and third trimesters.Given the effects of lithium on the conceptus, potentially safer alternatives may be required. The best case scenario is to counsel fecund women who require lithium to plan pregnancy, allowing for a temporary change in treatment regimen during the period of embryogenesis. If lithium therapy is reinstituted during the second and third trimesters, fetal monitoring for altered renal and endocrine function is important. Lithium requirements usually increase in the third trimester, but should be decreased in the peripartum period to avoid drug toxicity in the neonate and mother. Ultimately, the risk/benefit considerations must guide clinicians and patients in the decision to use lithium during pregnancy.

Among unipolar mood disorders, major depressive disorder (MDD) has traditionally been the most widely studied. There is, however, an alarming lack of extant research on the more mild mood disorders. Recent findings indicate that, collectively, milder unipolar mood disorders, such as dysthymic disorder (DD), and conditions specific to women, such as premenstrual dysphoric disorder (PMDD) and postpartum depression, functionally impair a large population of women. The course, mechanisms, and treatments of these illnesses are outlined, and specific areas of concern, including current available treatment applicability, gender differences in psychiatric testing, and the use of biological markers for the detection of illness, are detailed. Directions for future research are presented.

Background: Dysthymia is a chronic depressive condition that is quite prevalent. This condition can exact a significant toll on the general health and quality of life in the affected individual. Despite the frequency and consequences of dysthymia, however, the condition is often not diagnosed or treated. We present data on prior treatment from 410 patients with DSM-III-R dysthymia, primary type, early onset without concurrent major depression., Method: Axis I and II diagnoses were made by using the Structured Clinical Interviews for DSM-III-R, Patient Version (SCID-P) and SCID II for Personality Disorders. The Hamilton Rating Scale for Depression and the Clinical Global Impressions scale were also completed. Prior treatment was assessed, with special attention paid to previous antidepressant drug therapy and psychotherapy., Results: Although the mean duration of dysthymia was about 30 years and almost half of the patients had previous episodes of major depression, only 41.3% had been treated with antidepressants and 56.1% with psychotherapy. A past history of major depression increased the frequency of prior antidepressant pharmacotherapy (45.7%) and psychotherapy (59.4%) compared with no history of major depression (36.8% and 40.9%, respectively). Comorbid personality disorder increased the likelihood of prior psychotherapy (70.7% vs. 49.6%) while having no effect on past pharmacotherapy. A history of substance abuse did not affect the history of antidepressant or psychotherapy treatment. In this study, dysthymia and psychosocial outcomes improved with sertraline and imipramine treatment., Conclusion: Dysthymic patients in this sample were significantly undertreated. Newer antidepressant agents may alter the potential for pharmacotherapy interventions in this vulnerable population.

Premenstrual symptoms are common among young menstruating women, but the psychiatric disorder premenstrual dysphoric disorder (PMDD) is seen only in approximately 3% of this group. The symptom profile of PMDD has been empirically derived from a number of investigations including a large data base from five university centers. The most commonly reported symptoms are depression and mood swings, but a substantial number of women report tension and anxiety. Lifetime psychiatric illness is also common in women with PMDD, and although mood disorders predominate, past histories of anxiety disorders are also common, further suggesting an association between PMDD and anxiety disorders. The strongest data supporting such an association lie with challenge studies that have been used to provoke panic in panic patients and are effective in precipitating panic attacks in women with PMDD. Finally, treatments that are effective for anxiety disorders are also useful in the treatment of PMDD. In this paper, the above outlined relationship between anxiety disorders and PMDD is reviewed.

Premenstrual dysphoric disorder describes a subset of women who have severe premenstrual symptoms, including at least one mood symptom. It is included in DSM-IV under "Depressive Disorders Not Otherwise Specified." Criteria differentiating premenstrual dysphoric disorder from premenstrual syndrome are the requirements that patients have at least five symptoms, including one mood symptom; have impairment associated with the illness; and prospectively confirm the symptoms. After decades of treatment research on premenstrual dysphoria, the most consistent positive results have been found for selective antidepressants, primarily those that are active at serotonin receptors. Most studies have used continuous daily treatment for acute phase therapy. Further studies should define the role of intermittent and long-term maintenance therapies with these agents.

Premenstrual syndrome (PMS) is a common problem and patients with PMS are encountered by obstetricians, gynecologists, family practitioners, internists (general physicians) and psychiatrists. Despite several decades of biological research, the etiology of the disorder is still elusive. The introduction of a psychiatric category called premenstrual dysphoric disorder (PMDD), describing women with severe emotional premenstrual symptoms, has advanced biological treatment research by identifying a more homogeneous patient population. This paper aims to review our current understanding of the clinical presentation, underlying psycho-biology, and essentials of treatment for premenstrual dysphoric disorder.