Objectives: Premenstrual exacerbation of depression (PMED) is a variation of major depressive disorder (MDD) in which symptoms worsen during the premenstrual period. Breakthrough symptoms of PMED may occur despite effective antidepressant treatment in the rest of the cycle. This pilot study is designed to evaluate the effectiveness of variable dosing in PMED using the antidepressant sertraline.

Methods: Women diagnosed with PMED were started on sertraline (up to 50 or 100 mg/day). Those subjects demonstrating continued PMED on a constant dose (n = 9) were entered into a double-blind crossover protocol, receiving either placebo or an increase in sertraline premenstrually. Each subject was evaluated twice a month (follicular and luteal phase) by clinical evaluation, Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAM-D), and daily symptom diary and had blood collected for sertraline assay.

Results: Use of variable dosing resolved the PMED, such that there was no longer a significant difference in scores for the BDI and the HAM-D between the luteal and follicular phases during treatment with sertraline supplement (p = 0.32 and p = 0.53, paired t test, respectively). However, during the months with placebo supplement, the luteal and follicular phases showed a trend for differences for the BDI (p = 0.06, paired t test) and significant differences for the HAM-D (p = 0.02 paired t test); that is, the subjects retained the PMED pattern. Sertraline levels reflected the change in dosing pattern, with higher levels seen during the luteal phase during the months with sertraline supplement but no difference seen between luteal and follicular phases during months with placebo supplement (p = 0.07 and 0.69, paired t test, respectively).

Conclusions: The use of variable dosing in PMED increases the effectiveness of treatment.