Management of premenstrual dysphoric disorder

Premenstrual dysphoric disorder is a complex disorder characterized by severe physical and psychological symptoms. The pathophysiology and effective treatment of premenstrual dysphoric disorder are presented. Evidence for the effective treatment of premenstrual dysphoric disorder by correction of neuroendocrine abnormalities or suppression of cyclical ovarian activity is reviewed.     

Luteal phase sertraline treatment for premenstrual dysphoric disorder. Results of a double-blind, placebo-controlled, crossover study.

OBJECTIVE: To test the efficacy of late-luteal phase dosing of sertraline hydrochloride in women with moderate-to-severe premenstrual dysphoric disorder. This highly prevalent disorder often causes significant psychosocial impairment. DESIGN: Double-blind, crossover trial of each 2-menstrual cycle of baseline, sertraline treatment, and placebo. Randomization to sertraline treatment vs placebo occurred after a 2-cycle, drug-free period. SETTING: A large outpatient multispecialty clinic in central Texas. PATIENTS: Fifty-seven women aged 19 to 49 years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of premenstrual dysphoric disorder. INTERVENTIONS: Late-luteal phase treatment with sertraline hydrochloride in daily doses of 50 mg (cycle 1) followed by 100 mg (cycle 2) vs placebo. MAIN OUTCOME MEASURES: The 22-item calendar of premenstrual experiences was completed daily and constituted the primary outcome measure, consisting of a total score and behavioral and physical factor scores. RESULTS: A repeated-measures analysis of variance for crossover designs found a significant beneficial effect from sertraline treatment in improving the calendar of premenstrual experiences total (P < .01), behavioral factor (P < .01), and physical factor (P < .04) scores. Most women improved when taking sertraline, 50 mg, although a dose increase to 100 mg yielded further improvement in approximately 25% of women. Use of sertraline was extremely well tolerated; the only adverse event reported by 10% or more of women was insomnia in 8 (14%) of them. CONCLUSIONS: Luteal phase treatment with sertraline was a safe and effective treatment for moderate-to-severe premenstrual dysphoric disorder. Further controlled studies are needed to confirm the results of this preliminary study.     

Cost-effectiveness analysis of treatments for premenstrual dysphoric disorder

Background

Premenstrual syndrome (PMS) is reported to affect between 13% and 31% of women. Between 3% and 8% of women are reported to meet criteria for the more severe form of PMS, premenstrual dysphoric disorder (PMDD). Although PMDD has received increased attention in recent years, the cost effectiveness of treatments for PMDD remains unknown.

Objective

To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE).

Methods

A decision-analytic model was used to evaluate both direct costs (medication and physician visits) and clinical outcomes (treatment success, failure and discontinuation). Medication costs were based on average wholesale prices of branded products; physician visit costs were obtained from a claims database study of PMDD patients and the Agency for Healthcare Research and Quality. Clinical outcome probabilities were derived from published clinical trials in PMDD. The incremental cost-effectiveness ratio (ICER) was calculated using the difference in costs and percentage of successfully treated patients at 6 months. Deterministic and probabilistic sensitivity analyses were used to assess the impact of uncertainty in parameter estimates. Threshold values where a change in the cost-effective strategy occurred were identified using a net benefit framework.

Results

Starting therapy with DRSP/EE dominated both sertraline and paroxetine, but not fluoxetine. The estimated ICER of initiating treatment with fluoxetine relative to DRSP/EE was $US4385 per treatment success (year 2007 values). Cost-effectiveness acceptability curves revealed that for ceiling ratios ≥$US3450 per treatment success, fluoxetine had the highest probability (≥0.37) of being the most cost-effective treatment, relative to the other options. The cost-effectiveness acceptability frontier further indicated that DRSP/EE remained the option with the highest expected net monetary benefit for ceiling values ≤$US3900 per treatment success.

Conclusion

These analyses suggest that initiating therapy with DRSP/EE may be a cost-effective option in the treatment of PMDD.     

A symptom diary to assess severe premenstrual syndrome and premenstrual dysphoric disorder

The differentiation between premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) has been widely discussed. PMDD is listed as a mental disorder in the DSM-5, whereas PMS is not considered as a mental disorder in any diagnostic manual. Consequently, PMS is operationalized in different ways. Keeping a symptom diary is required to diagnose PMDD but is also recommended for PMS. The aim of our study was, therefore, to operationalize PMS and PMDD within a DSM-5-based symptom diary. We developed a symptom-intensity-score (SI-score) and an interference-score (INT-score) to evaluate the symptom diary. Ninety-eight women (aged 20–45 years) completed a symptom diary over two menstrual cycles, a retrospective screening for premenstrual symptoms, and answered additional impairment questionnaires from August 2013 to August 2015. The scores revealed moderate to good reliability (Cronbach’s α = 0.83–0.96). Convergent validity was shown by significant correlations with a retrospective screening, the Pain Disability Index, and the German PMS-Impact Questionnaire. Discriminant validity was indicated by low correlations with the Big Five Inventory-10. These scores may facilitate the evaluation of prospective symptom ratings in research and clinical practice. Future research should focus on continuing to validate the scores (e.g., in an ambulatory setting).     

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.     

Continuous oral levonorgestrel/ethinyl estradiol for treating premenstrual dysphoric disorder

BackgroundThe study was conducted to investigate continuous daily levonorgestrel 90 mcg/ethinyl estradiol 20 mcg (LNG/EE) on premenstrual dysphoric disorder (PMDD).Study DesignIn this multicenter, randomized, double-blind, placebo-controlled study, women with PMDD received LNG/EE (n=186) or placebo (n=181) daily for 112 days and completed the Daily Record of Severity of Problems (DRSP).ResultsMean DRSP change from baseline to late luteal phase was significantly greater with LNG/EE than placebo at the late luteal phase of the first estimated cycle (?30.52±1.73 [SE] vs. ?22.47±1.77; p<.001) and the worst 5 days during the last on-therapy estimated cycle (?26.77±1.83 vs. ?20.89±1.82; p=.016). Other primary end points were not statistically significant. Significantly more subject taking LNG/EE (52%) than placebo (40%) responded (≥50% improvement in the DRSP 7-day late luteal phase score and Clinical Global Impression of Severity score of ≥1 improvement) at last on-therapy cycle (p=.025).ConclusionsContinuous daily LNG 90 mcg/EE 20 mcg was well tolerated and may be useful for managing the physical, psychological and behavioral symptoms and loss of work productivity related to PMDD.     

258例经前焦虑性障碍的临床流行病学调查分析

目的:探讨经前焦虑性障碍(PMDD)的患病情况、中医症状及证候分布特点。方法:应用临床流行病学现况调查法对3 541例18～45岁女性门诊患者进行面访调查,根据《精神疾病诊断和统计手册》第4版(DSM-IV)确定被调查对象为患者,填写临床流行病学现况调查表,对不同年龄、职业等PMDD患者的中医症状及证候进行描述性分析。结果:调查对象中PMDD 258例,患病率为7.3%,不同年龄、职业、婚姻状况、文化程度的PMDD患病率差异有统计学意义(P<0.01)。PMDD患者的常见症状有15个,程度均较重,肝气逆证和肝气郁证为PMDD的主证与常见证,但以复合证为主。结论:PMDD患病群体呈现年轻化趋势,该病病机与肝失疏泄密切相关,故临床调理当以肝失疏泄立论,从肝论治为宜。     

Treatment of premenstrual dysphoric disorder with a new drospirenone-containing oral contraceptive formulation

PURPOSE: This multicenter, double-blind, placebo-controlled crossover study evaluated the efficacy of a new oral contraceptive (OC) formulation containing drospirenone 3 mg and ethinyl estradiol (EE) 20 mug in treating symptoms of premenstrual dysphoric disorder (PMDD). METHOD: The OC formulation or placebo was administered for 24 days in a 28-day cycle (24/4), rather than the usual 21-day active treatment, 7-day inert-pill regimen. Participants (N=64) were randomized to either study treatment for three cycles and then after a washout period of one treatment-free cycle switched to the alternate treatment. RESULTS: The mean decrease from baseline for total Daily Record of Severity of Problems (DRSP) scores while using drospirenone/EE was significantly greater than for placebo (-12.47, 95% CI=-18.28, -6.66; p<.001). A positive response (i.e., a score of 1 or 2 in the Clinical Global Impressions-Improvement scale) occurred in 61.7% and 31.8% of subjects while taking drospirenone/EE and placebo, respectively (p=.009). CONCLUSION: Drospirenone/EE, given in a 24/4 regimen, was superior to placebo for improving symptoms associated with PMDD.     

我国成人体重指数和腰围对相关疾病危险因素的预测价值: 适宜体重指数和腰围切点的研究

  目的  依托应用程序调查中国育龄女性经前期综合征,为进一步做好女性经期及经前期保健提供理论依据。  方法  于2015年1 — 12月在“大姨吗”应用程序首页发放调查问卷,共对24 670人进行一般情况及经前期综合征相关症状调查。  结果  随着年龄增加,经前期和经期便秘、痤疮、发热、腹泻、乳房胀痛、身体酸痛、食欲不佳、头痛、小腹坠胀、眩晕症状的发生率逐渐降低（均P < 0.01）;轻体重女性经前期和经期痤疮、发热、腹泻、乳房胀痛、身体酸痛、食欲不佳、头痛、眩晕的发生率高于其他体重组（P < 0.05）。有性生活的女性痤疮发生率（11.95 %）低于无性生活者（12.95 %）（P < 0.05）,而乳房胀痛（15.37 %）、身体酸痛（17.83 %）、眩晕（12.60%）的发生率均高于无性生活者的12.26 %、16.48 %、11.44 %（均P < 0.05）。已生育女性痤疮（10.17 %）、发热（5.79 %）、腹泻（7.57 %）、身体酸痛（16.83 %）、食欲不佳（13.52 %）、小腹坠胀（14.97 %）的发生率均低于未生育女性的13.30 %、8.15 %、10.70 %、18.12 %、14.72 %、19.16 %（均P < 0.05）。有痛经女性经前期和经期便秘（11.45 %）、痤疮（13.18 %）、发热（8.25 %）、腹泻（10.96 %）、乳房胀痛（15.89 % ）、身体酸痛（19.08 %）、食欲不佳（15.95 %）、头痛（14.77 %）、小腹坠胀（19.85 %）、眩晕（13.39 %）症状发生率均明显高于无痛经女性的7.94 %、9.02 %、5.27 %、6.59 %、10.63 %、12.51 %、10.47 %、10.03 %、12.17 %、8.94 %（均P < 0.01）。  结论  女性经期和经前期症状与年龄、体质指数、性生活、生育、月经是否规律、痛经等因素有关。     

Symptom patterns of premenstrual dysphoric disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders-IV

Premenstrual dysphoric disorder was included in an appendix of DSM-III-R (revised third edition of the Diagnostic and Statistical Manual of Mental Disorders) and DSM-IV to facilitate systematic research. Items contained in its set of research criteria were considered tentative. Only one previous study of premenstrual symptoms specifically addressed symptoms of premenstrual dysphoric disorder, and it did not use DSM-IV criteria. In the present study, prospectively measured symptoms of 99 women were analyzed using exploratory principal components analysis with orthogonal rotation on all 24 items derived from the 11 symptoms listed in DSM-IV. Variation was found across phases of cycle and groups, with five factors predominating: (1) anger/irritability, (2) depressed mood, (3) anxiety/tension, (4) decreased energy and interest with physical symptoms, and (5) eating problems.     

Reduction of quality-adjusted life years (QALYs) in patients with premenstrual dysphoric disorder (PMDD)

Purpose

Premenstrual dysphoric disorder (PMDD) refers to the depression that occurs during the premenstrual phase and remits soon after the onset of menses. It affects the quality of life (QOL) of patients with PMDD. Therefore, this preliminary survey from chart recordings aimed to understand the symptom appearance and QOL reduction patterns in patients with PMDD, and to examine the extent of the loss of their quality-adjusted life years (QALYs).

Methods

Participants were 66 untreated female patients with PMDD. Data on symptom appearance and QOL reduction during the menstrual cycle, and the EuroQoL-5D (EQ-5D) scores during the premenstrual phase and immediately after the completion of a menstrual period were collected.

Results

The mean EQ-5D score of the 66 patients with PMDD was 0.795 ± 0.120 (range 0.362–0.949), indicating that their expected mean loss of QALYs was about 0.14 years.

Conclusions

If untreated, PMDD is expected to cause a mean loss of QALYs of about 0.14 years. However, on accounting for the period from disease development to menopause, and subtracting the menstruation-free periods such as pregnancy and breastfeeding, patients with untreated PMDD are expected to experience a QALY loss of about 3 years during their lifetime.

     

Efficacy of sertraline for bulimia nervosa

OBJECTIVE: The current study examined the efficacy of sertraline in the treatment of individuals diagnosed with bulimia nervosa. METHOD: Eighteen women enrolled in an 8-week open trial of sertraline. Eating disorder psychopathology and depressive symptoms were assessed at baseline and at the end of the trial using both semistructured interviews and self-report questionnaires. RESULTS: Findings indicated significant reductions in eating disorder psychopathology, including the number of binges and purges per week, as well as significant reductions in depressive symptoms. In addition, participants did not experience significant weight gain or any other sertraline side effect assessed at the end of the trial compared with baseline. DISCUSSION: Findings from the current study indicate that sertraline is efficacious in the treatment of bulimia nervosa. A double-blind controlled trial of sertraline is recommended for future research.     

舍曲林治疗儿童情绪障碍的临床观察

目的 了解舍曲林在儿童情绪障碍治疗中的有效性、安全性、起效时间及有效剂量.方法 对147例应用舍曲林治疗的儿童情绪障碍患儿进行回顾性分析,项目包括有效率、舍曲林用量、起效时间及不良反应.结果 137例患儿遵医嘱定期复诊.治疗后2个月,有效率为80.3%(110/137),不良反应发生率为5.8%(8/137).舍曲林有效剂量为(47.9±19.0)mg/d,起效时间为(20.4±13.2)d;儿童强迫症舍曲林有效剂量[(58.7±26.2)mg/d)]显著高于抑郁障碍[(43.6±14.0)mg/d]、广泛性焦虑障碍[(44.4±10.6)mg/d]及恐怖性焦虑障碍[(43.5±15.5)mg/d](P值均<0.01);抑郁障碍起效时间[(14.0±6.1)d]较儿童强迫症[(26.6±16.3)d]、广泛性焦虑障碍[(22.3±13.9)d]和恐怖性焦虑障碍[(21.4±12.8)d]短(P值均<0.01).结论 舍曲林是治疗儿童情绪障碍的有效药物,起效时间在2～3周,不良反应轻,多数患儿能耐受.对抑郁障碍起效较快,对儿童强迫症有效剂量较大.

Abstract：

Objective To explore the efficacy, safety,time of drug taking effect and therapeutic dosage of sertraline in treatment of child emotional disorder. Method One hundred and forty-seven patientswith child emotional disorder were treated by sertraline and the efficacy rate, therapeutic dosage, the time of drug taking effect and adverse reaction was analyzed retrospectively. Results One hundred and thirty-seven patients were regular visited under supervision of a physician. Two months after treatment, the efficacy rate was 80.3%(110/137) and the rate of adverse reaction was 5.8%(8/137). The therapeutic dosage of sertraline was (47.9 + 19.0) mg/d. The time of drug taking effect was (20.4±13.2) d. The therapeutic dosage of sertraline in obsessive-compulsive disorder [(58.7±26.2) mg/d] was significantly higher than that in depression[(43.6±14.0) mg/d],anxiety disorder[(44.4±10.6) mg/d] and phobia[(43.5±15.5) mg/d](P < 0.01 ). The time of drug taking effect in depression[( 14.0±6.1 ) d] was significantly shorter than that in obsessive-compulsive disorder[(26.6±16.3) d,anxiety disorder [(22.3±13.9) d] and phobia [(21.4±12.8) d] (P <0.01). Conclusions Sertraline is an efficient and safe medicine in treatment of child emotional disorder. Its adverse reaction is slight and most patients can tolerate. But it takes higher therapeutic dosage in obsessive-compulsive disorder and the time of drug taking effect is earlier in depression than in other disorder.     

An overview of four studies of a continuous oral contraceptive (levonorgestrel 90 mcg/ethinyl estradiol 20 mcg) on premenstrual dysphoric disorder and premenstrual syndrome

BackgroundThis article presents an overview of four studies that evaluated a continuous oral contraceptive (OC) containing levonorgestrel (90 mcg) and ethinyl estradiol (20 mcg; LNG/EE) for managing premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS).Study DesignThree randomized, double-blind, placebo-controlled trials and one open-label, single-treatment substudy examined mean changes from baseline in the Daily Record of Severity of Problems (DRSP) or Penn Daily Symptom Rating (DSR).ResultsImprovements from baseline in mean DRSP and DSR scores were observed, but results were not consistent among the studies. Mean percent improvement of premenstrual symptoms ranged from 30% to 59% in controlled trials and 56% to 81% in an open-label substudy. A large placebo effect was also observed in the placebo-controlled studies. Continuous LNG/EE yielded a favorable safety profile.ConclusionsThese data, although not consistent, indicate that continuous LNG/EE may reduce the symptoms of PMDD and PMS, providing an option for women who are appropriate candidates for a continuous OC as a contraceptive, the approved indication for this medication.     

Premenstrual dysphoric disorder in Arab women: Validation and cultural adaptation of the Arabic version of the premenstrual screening tool

Premenstrual dysphoric disorder (PMDD) is not well-studied in Arab populations. The goal of this study was to validate the Arabic version of the Premenstrual Symptoms Screening Tool (PSST) using the DSM diagnosis of PMDD as the gold standard. The PSST was translated and culturally adapted using back translation and the approval of the original author. We recruited 194 adult women (between October 2013 and March 2014) from two primary care centers in Doha, Qatar. A psychiatrist determined the diagnosis using the semi-structured Mini International Neuropsychiatric Interview, and another rater blinded to the diagnosis finalized the Arabic PSST and administered other clinical questionnaires. The data showed that premenstrual symptoms and PMDD were observed in about 37 percent and 15 percent, respectively, of the women enrolled. The mean age of the women with PMDD according to the PSST was about 30 years, and the majority had children. The Arabic PSST showed high specificity of 95.6 percent but low sensitivity of 26.7 percent. A factor analysis of the different items in Arabic PSST showed that the Arabic PSST could detect the cases with definite PMDD and thus can be a useful tool in primary care settings as this treatable disorder is underdiagnosed in the Arab populations.