Premenstrual dysphoric disorder: General overview, treatment strategies, and focus on sertraline for symptom-onset dosing Original paper

What was studied?

This paper studied the efficacy and tolerability of symptom-onset dosing of sertraline, a selective serotonin reuptake inhibitor (SSRI), for the treatment of premenstrual dysphoric disorder (PMDD). The focus was on assessing whether administering sertraline starting at the onset of PMDD symptoms, rather than continuous or luteal-phase dosing, could effectively reduce symptom severity and improve clinical outcomes over six menstrual cycles. The study also explored the side effect profile and discontinuation symptoms associated with this targeted treatment approach.

Who was studied?

The study population comprised 252 women with prospectively confirmed PMDD, aged approximately 34 years on average, predominantly white (around 70%), and without significant medical or psychiatric comorbidities. These participants were randomized into two groups: 125 women received flexible doses of sertraline (50–100 mg/day) beginning at symptom onset and continuing until menstruation began, while 127 women received placebo treatment following the same schedule.

What were the most important findings?

The study demonstrated that symptom-onset treatment with sertraline significantly reduced the severity of PMDD symptoms compared to placebo. Specifically, women treated with sertraline showed statistically significant improvements in depressive symptoms as measured by clinician-rated scales and a significant reduction in the daily record of problem severity, including the anger/irritability subscale. While the reduction in premenstrual tension ratings narrowly missed statistical significance, sertraline outperformed placebo in global improvement ratings and had higher clinical response rates (67% vs. 52%). Noticeably, emission rates were not significantly different. The average duration of sertraline use was only about seven days per menstrual cycle, minimizing exposure to the drug and related side effects. Adverse effects, primarily nausea and insomnia, were more common in the sertraline group, but abrupt discontinuation did not lead to withdrawal symptoms. These findings indicate that targeted, short-term SSRI treatment timed to symptom onset is effective and well tolerated in managing PMDD.

What are the greatest implications of this study?

This research challenges traditional views that antidepressants require continuous administration to be effective in PMDD treatment by demonstrating that symptom-onset dosing with sertraline is both efficacious and has a favorable side effect profile. This approach minimizes medication exposure and associated adverse effects, potentially improving adherence and reducing treatment costs. It provides a practical strategy to manage PMDD symptoms precisely when needed, aligning with the disorder’s cyclical nature. Future research is needed to compare symptom-onset dosing directly with luteal-phase and continuous dosing regimens and to explore treatment strategies for non-responders to symptom-onset sertraline. Clinically, this study supports personalized, flexible pharmacotherapy for PMDD, enhancing therapeutic outcomes while mitigating risks.