快樂小藥師 Im pharmacist nichts glücklich

News Author: Laurie Barclay, MD

May 19, 2009 — Relapse of severe premenstrual syndrome (PMS) in women whose symptoms are relieved by the antidepressant sertraline occurs in 40% to 60% of women within 6 to 8 months after stopping medication, according to the results of a study reported in the May issue of the Archives of General Psychiatry.

"The duration of treatment after achieving a satisfactory response is unknown in the treatment of premenstrual syndrome," write Ellen W. Freeman, PhD, from the University of Pennsylvania School of Medicine in Philadelphia, and colleagues. "This information is needed in view of the improvement provided by medication vs. the adverse effects and costs of drugs."

The goal of this study was to compare rates of relapse and time to relapse for short-term vs long-term treatment with sertraline hydrochloride given during the luteal phase of the menstrual cycle. In this 18-month survival study at an academic medical center, 174 patients with PMS or premenstrual dysphoric disorder (PMDD) underwent a randomized, double-blind switch to placebo after 4 or 12 months of sertraline treatment. The main endpoint of the study was relapse, defined as symptoms returning to the entry criterion level as evaluated with daily ratings.

During long-term sertraline treatment, the relapse rate was 41% vs 60% after short-term treatment (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.34 - 0.98; P = .04). Median time to relapse was 8 months vs 4 months, respectively. Compared with patients in the lower symptom severity group, those with severe symptoms at baseline were more likely to have a relapse (HR, 2.02; 95% CI, 1.18 - 3.41; P = .01) and were also more likely to experience relapse after short-term treatment (P = .03).

In the lower symptom severity group, duration of treatment did not affect relapse (P = .50). Participants who experienced remission were least likely to have a relapse (HR, 0.22; 95% CI, 0.10 - 0.45; P < .001). Findings were similar for additional analysis comparing relapse in each group during the first 6 months of placebo treatment.

"The relapse rate was significantly greater after short-term treatment compared with long-term treatment," the study authors write. "The relapse rate was also high during extended drug treatment."

"Subjects with severe symptoms at baseline were most likely to experience relapse, and relapse occurred more swiftly regardless of treatment duration," the study authors conclude. "These findings suggest that the severity of symptoms at baseline and symptom remission with treatment should be considered in determining the duration of treatment."

The National Institute of Child Health and Human Welfare supported this study. Sertraline hydrochloride was provided by Pfizer Inc. Some of the study authors have disclosed various financial relationships with Pfizer Inc; Berlex Laboratories, LLC; Forest Research Institute, Inc; Pherin Pharmaceuticals, Inc; Wyeth; Xanodyne Pharmaceuticals, Inc; Cephalon, Inc; DOV Pharmaceuticals Inc; Eli Lilly and Co; Epix Pharmaceuticals, Inc; Hoffman-LaRoche Inc; Jazz Pharmaceuticals, Inc; Johnson & Johnson; Novartis AG; Sanofi-Synthelabo Research; Bristol-Meyers Squibb Co; Genaissance Pharmaceuticals, Inc; GlaxoSmithKline; Merck & Co, Inc; Pamlab LLC; and/or Somerset Pharmaceuticals, Inc.

Arch Gen Psychiatry. 2009;66:537-544.

Clinical Context

Study Highlights

• 174 women aged 18 to 45 years with PMS or PMDD were randomly assigned to receive sertraline during luteal phase for 4 or 12 months.
• Inclusion criteria were regular menstrual cycles of 22 to 35 days for at least 6 months, premenstrual symptoms for at least 1 year, probable ovulation by urine test, and good health assessed by physical examinations and laboratory tests.
• Exclusion criteria were any major axis I psychiatric diagnosis in the past year, substance abuse in the past year, psychosis or bipolar disorder, psychotropic medication or any PMS therapy, pregnancy, breast-feeding, hysterectomy, endometriosis, irregular menstrual cycles, lack of contraception, or serious medical illness.
• Severe PMS was diagnosed by a total premenstrual score of at least 80 and at least 50% increase from a postmenstrual score rated by subjects daily for 17 Daily Symptom Report items and a rating of at least 4 on patient global ratings of functioning in work, family life, social activity, and interference.
• The 3-month screening period included 1 month of single-blind placebo use.
• 87 patients in the short-term group received sertraline for 4 months, then placebo for 14 months.
• 87 patients in the long-term group received sertraline for 12 months, then placebo for 6 months.
• Short-term and long-term groups had similar baseline characteristics: mean age (32.1 - 33.6 years), employment, education, partner, oral contraceptive use, race, children, PMS duration, Daily Symptom Report score, Hamilton Depression Rating Scale stress score, depression history, and PMDD.
• Initial sertraline dose was 50 mg/day.
• Mean sertraline dose of 89 mg/day did not differ between short-term and long-term groups.
• Symptoms were assessed monthly.
• Screening average Daily Symptom Report scores were used to classify symptom severity as high (> 169), mid (169 - 122), and low (121 - 80).
• 125 (72%) of 174 patients improved, with no significant difference between the groups.
• Improvement occurred in the first month in 37%, the second month in 62%, the third month in 69%, and the fourth month in 70%.
• The main outcome measure of relapse rate was lower with long-term vs short-term treatment (41% vs 60%; HR, 0.58; 95% CI, 0.34 - 0.98; P = .04).
• Median time to relapse was longer with long-term vs short-term treatment (8 months vs 4 months).
• More severe baseline symptoms vs lower symptom severity were linked with higher relapse rates (70% vs 41%; HR, 2.02; 95% CI, 1.18 - 3.41; P = .01).
• Among patients in the high symptom severity group, relapse was greater for short-term vs long-term treatment (83% vs 58%; P = .03)
• Among patients in the low symptom severity group, relapse rates were similar for short-term and long-term treatment (49% vs 33%).
• Remission vs less complete recovery was associated with lower relapse rates (22% vs 67%; HR, 0.22; 95% CI, 0.10 - 0.45; P < .001), regardless of treatment duration or symptom severity.
• Secondary analysis comparing time vs relapse for each group in the first 6 months of placebo treatment showed similar results.
• Study limitations included no established definitions of improvement, remission, and relapse; observed difference in relapse rate between groups being lower vs prestudy estimates; subjects healthy, predominantly white, and aged in late 20s to mid-30s; and lack of treatment strategies for patients who experienced relapse or did not improve.

Clinical Implications

• In women with PMS or PMDD, long-term vs short-term treatment with sertraline is associated with a lower relapse rate and a longer time to relapse.
• In women with PMS or PMDD, those with severe symptoms are more likely to have relapse and to have relapse with short-term sertraline treatment. Relapse is not affected by treatment duration in those with less severe symptoms. Relapse is less likely in those who had remission.