Does Adding Fluoxetine to Combined Oral Contraceptives Containing Drospirenone Improve the Management of Severe Premenstrual Syndrome? A 6-Month Randomized Double-Blind Placebo-Controlled Three-Arm Trial

To compare efficacy of combined use of fluoxetine and combined oral contraceptives (COC) versus COC alone in treating severe premenstrual syndrome (PMS), a randomized double-blind placebo-controlled three-arm trial was conducted at Cairo and Beni-Suef University Hospitals. PMS was diagnosed prospectively using the Daily Record of Severity of Problems (DRSP). Three hundred women with severe PMS were randomly divided into three equal groups. Group 1 received oral fluoxetine 20 mg daily in addition to COC containing drospirenone daily for 21 days. Group 2 received COC containing drospirenone daily for 21 days in addition to daily oral placebo. Group 3 received placebo similar to COC and oral placebo similar to fluoxetine. Drug duration was 6 months, and women kept daily records of their symptoms using the Daily Record of Severity of Problems (DSRP) form. The main outcome was the number of women with improved PMS in the final cycle of treatment. Women with improved PMS decreased progressively between groups during last treatment month (65% vs. 50% and 2% respectively; p < 0.0001). Combined use of fluoxetine and COC containing drospirenone is superior to COC in severe PMS.