Changes in quality of life and sleep across the perinatal period in women with mood disorders.

INTRODUCTION: The perinatal period represents a time of significant life changes associated with increases in sleep difficulties, depression, and potentially impaired quality of life (QoL). Associations between QoL and sleep among women with perinatal depression are poorly understood, and changes in QoL across the perinatal period have received little attention. METHODS: Participants were the treatment-as-usual group (n = 23) from a clinical trial testing an intervention for perinatal mood disorders. They completed the WHOQOL-Bref, had depression assessed with the HAM-D-17, and wore wrist actigraphs to estimate sleep for 1 week during third trimester and at 6 weeks postpartum. RESULTS: Higher education level was associated with better environmental QoL during pregnancy (p = .044) and presence of older children was associated with worse social QoL postpartum (p = .045). Psychological health QoL worsened (p = .014) across the perinatal period. Total sleep time (p = .001) and sleep efficiency (p = .008) decreased from third trimester to postpartum week 6, but sleep measures were not associated with QoL at either time point. Depressive symptoms decreased from pregnancy to postpartum week 6 and were inversely associated with postpartum physical and social QoL (p = .031 and .048). DISCUSSION: Factors contributing to self-rated QoL are variable across multiple domains during the perinatal period. QoL among our participants was lower than population norms. In our sample of women with depression and/or anxiety, QoL was related to postpartum depressive symptoms, but not to objectively measured sleep quality, quantity, or timing. Links between QoL and sleep may be inherently complex in perinatal women.

Patient choice of treatment for postpartum depression: a pilot study.

OBJECTIVE: The lack of systematic efficacy research makes the selection of optimal treatment for postpartum depression (PPD) difficult. Moreover, the treatment decisions for women with PPD who are breastfeeding are heavily influenced by their concerns about infant exposure to antidepressant medication. The objective of this pilot trial was to examine the clinical characteristics of women with PPD associated with treatment selection. METHOD: This open pilot trial offered 23 women with PPD one of 3 treatment options: sertraline, interpersonal psychotherapy (IPT), or their combination administered in an outpatient mental health setting over 12 weeks. Baseline and treatment outcome measures included the Hamilton Rating Scale for Depression (HRSD), the Beck Depression Inventory (BDI) and the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Completers across all 3 treatment groups (n = 18) experienced significant clinical improvement with each of the 3 treatment modalities on the HRSD (p < 0.001), BDI (p < 0.001) and EPDS (p < 0.001). There were trends for women with a prior depression to more frequently choose sertraline as a treatment (alone or with IPT, p = 0.07), and for women who were breastfeeding to choose sertraline (alone or with IPT, p = 0.10) less frequently. CONCLUSION: In this small sample of women with PPD, most women chose IPT with or without sertraline. A larger randomized study could further confirm the suggested predictors of treatment selection identified in this study: previous depression and breastfeeding status.

A psychiatric mother-baby day hospital for pregnant and postpartum women.

Major depression and other psychiatric disorders are common during pregnancy and the postpartum period, yet these disorders remain largely under-diagnosed and under-treated. Developing programs that are uniquely tailored to meet the needs of perinatal psychiatric patients can improve both the quality and acceptability of care. In this report, we describe the development and implementation of a novel mother-baby day hospital service designed to meet the mental health needs of this special population, and present preliminary data regarding treatment acceptability and effectiveness. Our experience using this model of care for the past five years has suggested that specialized units such as this one represent an acceptable, effective, fiscally viable approach to the care of pregnant and postpartum psychiatric patients. Further research is needed to more thoroughly assess the effectiveness of this type of specialized perinatal service.

Premenstrual disorders: bridging research and clinical reality.

INTRODUCTION: As with a number of emotional disorders, premenstrual complaints lie on a continuum dictated by severity, number and type of symptoms experienced. Women with premenstrual dysphoric disorder (PMDD) generally constitute the most symptomatic subgroup among those experiencing premenstrual symptoms. Included in the Diagnostic and Statistical Manual IV (DSM-IV) criteria for PMDD is a requirement for a minimum of 5 symptoms and for confirmation of these symptoms over two months by concurrent symptom ratings. These requirements likely influence critical patient characteristics rendering trial participants and typical patients seeking treatment, very different. METHODS: Women were recruited from 6 primary care obstetric-gynecological practices for participation in an open trial assessing the effectiveness of a serotonin reuptake inhibitor as a treatment for subsyndromal (3-4 symptoms) and syndromal (>4 symptoms) PMDD. Women were screened with the Brief Patient Health Questionnaire and Last Menstrual Period Module. Eligible women were invited to chart symptoms daily for one cycle using the Daily Record of Severity of Problems. Current comorbidity was allowed if women experienced a cyclic change in mood and behavioral symptoms. RESULTS: 47% of 904 women screened in practice settings (n=426) endorsed current PMS symptoms. Of this group, 174 (41%) were not interested in receiving treatment through a research study, 152 (36%) were not eligible to receive treatment (symptoms not severe enough, subsequently declined premenstrual symptom worsening, were already taking a psychotropic or wanted to conceive), 10% were lost to follow-up or had incomplete questionnaires, and 41 (10%) agreed to chart. Of women who charted, 9 (22%) verified symptoms. 93 women (22% of the 426) had comorbid MDD, 23 (5.4%) had minor depressive disorder and 61 (14%) had panic disorder. 24% of women with possible PMDD endorsed suicidal thoughts at any level (several days, more than half the days or every day); 20% endorsed these thoughts for several days. These results are used as a springboard to discuss how treatment results from efficacy trials may differ from treatment results that include women seeking treatment in usual care settings. CONCLUSION: These preliminary findings show that many women in primary care ob-gyn settings endorse serious premenstrual symptoms and have concurrent psychiatric conditions. Despite this, interest in study participation was low. This occurred even though the current study employed procedures that were much less rigorous than those used in the typical efficacy study. More work is needed to explore how the selectivity of patients included in clinical trials may bias estimates of how effective many agents will be in actual clinical practice.

A double-blind, placebo-controlled trial of fluvoxamine in binge eating disorder: a high placebo response.

Twenty subjects with binge eating disorder were randomly assigned to flexible-dose fluvoxamine or placebo for 12 weeks. A significant reduction in binge frequency, Beck Depression Inventory scores and the eating concern, shape concern and weight concern subscales of the Eating Disorder Examination were noted for both fluvoxamine (n = 9) and placebo (n = 11) groups. There were no significant differences between fluvoxamine and placebo for any treatment outcome variables. The findings from this small trial contribute to the inconsistent results of antidepressant studies in binge eating disorder.

Efficacy of sertraline in preventing relapse of posttraumatic stress disorder: results of a 28-week double-blind, placebo-controlled study.

OBJECTIVE: The study examined the efficacy of sertraline, compared with placebo, in sustaining improvement and preventing relapse over 28 weeks in patients with posttraumatic stress disorder (PTSD) who had completed a 12-week double-blind, placebo-controlled acute treatment study and a subsequent 24-week open-label study of continuation treatment with sertraline. METHOD: Ninety-six patients were randomly assigned, in a double-blind design, to 28 weeks of maintenance treatment with sertraline (50-200 mg, N=46; 78% were women) or placebo (N=50; 62% were women). Measures used in biweekly assessments included the Clinician-Administered PTSD Scale, the Impact of Event Scale, and the Clinical Global Impression severity and improvement ratings. Kaplan-Meier analyses were used to estimate time to discontinuation from the study due to relapse, relapse or study discontinuation due to clinical deterioration, and acute exacerbation. RESULTS: Continued treatment with sertraline yielded lower PTSD relapse rates than placebo (5% versus 26%). Patients who received placebo were 6.4 times as likely to experience relapse as were patients who received sertraline. Kaplan-Meier analyses confirmed the protective effect of sertraline in significantly extending time in remission. The ability of sertraline to sustain improvement was comparable across the three core PTSD symptom clusters (reexperiencing/intrusion, avoidance/numbing, and hyperarousal). A regression analysis found early response during acute treatment to be associated with a more than 16-fold reduced risk of relapse after placebo substitution. Sertraline, at a mean endpoint dose of 137 mg, was well tolerated, with no sertraline-related adverse events observed at a rate of 10% or higher. CONCLUSIONS: The results provide evidence for the ability of sertraline both to sustain improvement in PTSD symptoms and to provide prophylactic protection against relapse.

Evaluation of a unique oral contraceptive in the treatment of premenstrual dysphoric disorder.

Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). This is the first trial of a unique oral contraceptive containing a combination of drospirenone (DRSP, 3 mg) and ethinyl estradiol (EE, 30 microg) for the treatment of PMDD. DRSP is a spironolactone-like progestin with antiandrogenic and antimineralocorticoid activity. Spironolactone has been shown to be beneficial in PMS, whereas oral contraceptives have shown conflicting results. In this double-blind, placebo-controlled trial, 82 women with PMDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM IV]) were randomized to receive DRSP/EE or placebo for three treatment cycles. The primary end point was change from baseline in luteal phase symptom scores as assessed on the Calendar of Premenstrual Experiences (COPE) scale. Patients treated with DRSP/EE showed a numerically greater change from baseline compared with those treated with placebo on each of the 22 COPE items and each of the 4 symptom factors. Between-group differences in symptom improvement reached statistical significance in factor 3 only (appetite, acne, and food cravings, p = 0.027). The secondary end points, Beck Depression Inventory (BDI) and Profile of Mood States (PMS), were consistent with the primary end point in that patients treated with the oral contraceptive showed a numerically greater improvement from baseline compared with those treated with placebo. The results of this study show a consistent trend in the reduction of symptoms that suggested a beneficial effect of DRSP/EE for the treatment of PMDD, despite limitations of the study design.

Postpartum depression in women receiving public assistance: pilot study of an interpersonal-therapy-oriented group intervention.

OBJECTIVE: This study investigated whether a preventive intervention based on the principles of interpersonal psychotherapy administered to pregnant women would reduce the risk of postpartum major depression. METHOD: Thirty-seven pregnant women receiving public assistance who had at least one risk factor for postpartum depression were randomly assigned to a four-session group intervention or to a treatment-as-usual condition. Thirty-five of the women completed the study. Structured diagnostic interviews were administered to assess for postpartum major depression. RESULTS: Within 3 months after they gave birth, six (33%) of the 18 women in the treatment-as-usual condition had developed postpartum major depression, compared with none of the 17 women in the intervention condition. CONCLUSIONS: A four-session interpersonal-therapy-oriented group intervention was successful in preventing the occurrence of major depression during a postpartum period of 3 months in a group of financially disadvantaged women.

Premenstrual dysphoria and the serotonin system: pathophysiology and treatment.

The inclusion of research diagnostic criteria for premenstrual dysphoric disorder (PMDD) in the DSM-IV recognizes the fact that some women have extremely distressing emotional and behavioral symptoms premenstrually. PMDD can be differentiated from premenstrual syndrome (PMS), which presents with milder physical symptoms, headache, and more minor mood changes. In addition, PMDD can be differentiated from premenstrual magnification of physical and/or psychological symptoms of a concurrent psychiatric and/or medical disorder. As many as 75% of women with regular menstrual cycles experience some symptoms of PMS, according to epidemiologic surveys. PMDD is much less common; it affects only 3% to 8% of women in this group. The etiology of PMDD is largely unknown, but the current consensus is that normal ovarian function (rather than hormone imbalance) is the cyclical trigger for PMDD-related biochemical events within the central nervous system and other target organs. The serotonergic system is in close reciprocal relationship with the gonadal hormones and has been identified as the most plausible target for interventions. Thus, beyond the conservative treatment options such as lifestyle and stress management, other nonantidepressant treatments, or the more extreme interventions that eliminate ovulation altogether, the serotonin reuptake inhibitors (SRIs) are emerging as the most effective treatment option for this population. Results from several randomized, placebo-controlled trials in women with PMDD have clearly demonstrated that the SRIs have excellent efficacy and minimal side effects. More recently, several preliminary studies indicate that intermittent (premenstrual only) treatment with selective SRIs is equally effective in these women and, thus, may offer an attractive treatment option for a disorder that is itself intermittent.

Non-antidepressant treatment of premenstrual syndrome.

Although selective serotonin reuptake inhibitors are considered the first-line treatment option for premenstrual syndrome, several other such options are also available. Multiple studies have indicated that medications that suppress ovulation alleviate premenstrual emotional and physical symptoms. However. the use of such medications, such as the gonadotropin-releasing hormone agonists, leads to prolonged low estrogen levels and cardiac and osteoporotic health risks. A recent double-blind, placebo-controlled study of 466 women with premenstrual syndrome reported that calcium was effective in reducing emotional, behavioral, and physical premenstrual symptoms. Recent preliminary trials have suggested efficacy for cognitive therapy, light therapy, and tryptophan. Future studies of diet recommendations, exercise, relaxation, magnesium, nonsteroidal anti-inflammatory drugs, diuretics, opiate antagonists, and alternative therapies are needed.

Antidepressant treatment of posttraumatic stress disorder.

Recent large double-blind, placebo-controlled trials have indicated that sertraline is an effective and well-tolerated treatment for posttraumatic stress disorder (PTSD). The avoidance/numbing symptom cluster improved the most significantly with sertraline, but significant improvements were also noted for the intrusive/reexperiencing and arousal symptom clusters. Smaller double-blind, placebo-controlled trials have also indicated that fluoxetine is an effective treatment for PTSD. Multiple small, open studies with other selective serotonin reuptake inhibitors and newer antidepressants indicate that these medications show some promise. Older studies indicate some efficacy for tricyclic antidepressants, and monoamine oxidase inhibitors are a reasonable choice, particularly for intrusive/reexperiencing symptoms.

Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial.

CONTEXT: Despite the high prevalence, chronicity, and associated comorbidity of posttraumatic stress disorder (PTSD) in the community, few placebo-controlled studies have evaluated the efficacy of pharmacotherapy for this disorder. OBJECTIVE: To determine if treatment with sertraline hydrochloride effectively diminishes symptoms of PTSD of moderate to marked severity. DESIGN: Twelve-week, double-blind, placebo-controlled trial preceded by a 2-week, single-blind placebo lead-in period, conducted between May 1996 and June 1997. SETTING: Outpatient psychiatric clinics in 8 academic medical centers and 6 clinical research centers. PATIENTS: A total of 187 outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition diagnosis of PTSD and a Clinician Administered PTSD Scale Part 2 (CAPS-2) minimum total severity score of at least 50 at baseline (mean age, 40 years; mean duration of illness, 12 years; 73% were women; and 61.5% experienced physical or sexual assault). INTERVENTION: Patients were randomized to acute treatment with sertraline hydrochloride in flexible daily dosages of 50 to 200 mg/d, following 1 week at 25 mg/d (n=94); or placebo (n=93). MAIN OUTCOME MEASURES: Baseline-to-end-point changes in CAPS-2 total severity score, Impact of Event Scale total score (IES), and Clinical Global Impression-Severity (CGI-S), and CGI-Improvement (CGI-I) ratings, compared by treatment vs placebo groups. Results Sertraline treatment yielded significantly greater improvement than placebo on 3 of the 4 primary outcome measures (mean change from baseline to end point for CAPS-2 total score, -33.0 vs -23.2 [P =.02], and for CGI-S, -1.2 vs -0.8 [P=.01]; mean CGI-I score at end point, 2.5 vs 3.0 [P=.02]), with the fourth measure, the IES total score, showing a trend toward significance (mean change from baseline to end point, -16.2 vs -12.1; P=.07). Using a conservative last-observation-carried-forward analysis, treatment with sertraline resulted in a responder rate of 53% at study end point compared with 32% for placebo (P=.008, with responder defined as >30% reduction from baseline in CAPS-2 total severity score and a CGI-I score of 1 [very much improved], or 2 [much improved]). Significant (P<.05) efficacy was evident for sertraline from week 2 on the CAPS-2 total severity score. Sertraline had significant efficacy vs placebo on the CAPS-2 PTSD symptom clusters of avoidance/numbing (P=.02) and increased arousal (P=.03) but not on reexperiencing/intrusion (P=.14). Sertraline was well tolerated, with insomnia the only adverse effect reported significantly more often than placebo (16.0% vs 4.3%; P=.01). CONCLUSIONS: Our data suggest that sertraline is a safe, well-tolerated, and effective treatment for PTSD.

Psychosocial functioning in women with premenstrual dysphoric disorder before and after treatment with sertraline or placebo.

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.

Chronicity in posttraumatic stress disorder (PTSD) and predictors of course of comorbid PTSD in patients with anxiety disorders.

The purpose of this study was to examine the course of comorbid posttraumatic stress disorder (PTSD) in 54 patients with another anxiety disorder. Using a prospective longitudinal design, the present study found that during the first 5 years of follow-up the probability of full remission from a chronic episode of PTSD was .18. Findings from this and other research confirm clinical impressions that a substantial number of people never fully remit from their PTSD even after many years. Variables associated with a longer time to remit from an episode of chronic PTSD were a history of alcohol abuse and a history of childhood trauma.

Is premenstrual dysphoric disorder a distinct clinical entity?

Does the evidence now available support the concept of premenstrual dysphoric disorder (PMDD) as a distinct clinical disorder such that the relative safety and efficacy of potential treatment can be evaluated? In a roundtable discussion of this question, a wealth of information was reviewed by a panel of experts. The key characteristics of PMDD, with clear onset and offset of symptoms closely linked to the menstrual cycle and the prominence of symptoms of anger, irritability, and internal tension, were contrasted with those of known mood and anxiety disorders. PMDD displays a distinct clinical picture that, in the absence of treatment, is remarkably stable from cycle to cycle and over time. Effective treatment of PMDD can be accomplished with serotinergic agents. At least 60% of patients respond to selective serotonin reuptake inhibitors (SSRIs). In comparison with other disorders, PMDD symptoms respond to low doses of SSRIs and to intermittent dosing. Normal functioning of the hypothalamic-pituitary-adrenal (HPA) axis, biologic characteristics generally related to the serotonin system, and a genetic component unrelated to major depression are further features of PMDD that separate it from other affective (mood) disorders. Based on this evidence, the consensus of the group was that PMDD is a distinct clinical entity. Potential treatments for this disorder can now be evaluated on this basis to meet the clear need for effective therapy.

Interactive case challenge. Dysphoric disorders in women: a case of premenstrual syndrome.

When this woman's long-standing PMS grows progressively more severe over the 3 years following the birth of her third child, what pharmacologic and nonpharmacologic treatments would you recommend? Symptoms of mood swings, irritability, and anxiety occur in many women during the premenstrual phase of the menstrual cycle. Several promising treatment options now exist for women whose symptoms are severe and interfere with daily functioning. These include nonpharmacologic as well as pharmacologic interventions, such as serotonergic antidepressants, anxiolytics, and hormones that suppress ovulation. When PMS becomes intolerably severe for this 36-year-old mother of 3 children--all under 10 years of age--she seeks treatment.

Premenstrual syndrome.

The advances in the careful screening and diagnosis of women with PMS has led to the ability to conduct epidemiologic, etiologic, and treatment studies in well-defined samples of women. Prospective symptom charting, scoring methods, and careful clinical psychiatric and medical evaluation are necessary to rule out concurrent psychiatric and medical disorders. Studies of women with PMDD have suggested several promising pharmacologic treatment options. Whether these treatment options are also successful for women with milder premenstrual symptoms, with premenstrual exacerbation of underlying conditions, or with premenstrual symptoms superimposed on underlying psychiatric and medical conditions remains to be studied. Treatment of premenstrual symptoms by pharmacologic or nonpharmacologic methods may be unsuccessful if the underlying psychiatric or medical condition is not addressed first.

Dysphoric disorders in women: a case of perinatal depression.

During her third pregnancy, a woman becomes preoccupied with illness and death. When the dysphoria continues after her child is born, how would you evaluate and manage the problem?

Use of dialectical behavior therapy in a partial hospital program for women with borderline personality disorder.

Dialectical behavior therapy, an outpatient psychosocial treatment for chronically suicidal women with borderline personality disorder, has been adapted for use in a partial hospital program for women. Patients attend the program for a minimum of five days of individual and group therapy, and full census is 12 women. About 65 percent of participants meet at least three criteria for borderline personality disorder, and most have suicidal and self-injurious behavior. Their comorbid diagnoses include trauma-related diagnoses and anxiety disorders, severe eating disorders, substance abuse, and depression. The partial hospital program is linked to an aftercare program offering six months of outpatient skills training based on dialectical behavior therapy. Both programs focus on teaching patients four skills: mindfulness (attention to one's experience), interpersonal effectiveness, emotional regulation, and distress tolerance. Two years of operation of the women's partial hospital program provides promising anecdotal evidence that dialectical behavioral therapy, an outpatient approach, can be effectively modified for partial hospital settings and a more diverse population.

Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial. Sertraline Premenstrual Dysphoric Collaborative Study Group.

CONTEXT: Premenstrual dysphoric disorder is an important cause of symptoms and functional impairment in menstruating women. OBJECTIVE: To evaluate the efficacy of sertraline hydrochloride for treatment of premenstrual dysphoria by measuring changes in symptom expression and functional impairment. DESIGN: Two screening cycles followed by 1 single-blind placebo cycle and 3 cycles of randomized, double-blind, placebo treatment. SETTING: Twelve university-affiliated outpatient psychiatry and gynecology clinics. PATIENTS: Of the 447 women who requested participation, 243 met criteria for premenstrual dysphoric disorder and were randomized; 200 women completed the study. INTERVENTION: A flexible (50-150 mg) daily dose of sertraline hydrochloride. MAIN OUTCOME MEASURES: The Daily Record of Severity of Problems, Hamilton Rating Scale for Depression, Clinical Global Impression Scale, and Social Adjustment Scale. RESULTS: Mean (+/-SD) total daily symptom scores decreased significantly (P<.001) in the sertraline-treated (64+/-22 to 44+/-19) compared with the placebo-treated (62+/-22 to 54+/-24) groups. Significant improvement (P<.05) was found for all clinically derived symptom clusters (depressive, physical, and anger/irritability symptoms). Hamilton Rating Scale for Depression scores decreased by 44% and 29% in the sertraline and placebo groups, respectively (P<.002). End-point global ratings showed much or very much improvement in 62% of the active treatment group and 34% of the placebo treatment group (P<.001). Reported functional impairment was substantial at baseline. Improvement in psychosocial functioning with treatment was similar to what is found in studies of major depression. CONCLUSIONS: Sertraline was significantly better than placebo for treatment of premenstrual dysphoria as reflected by symptomatic improvement and change in reported functional impairment. Serotonin reuptake inhibitors such as sertraline are useful therapeutic options for women with premenstrual dysphoria.