Weekly luteal-phase dosing with enteric-coated fluoxetine 90 mg in premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled clinical trial.
BACKGROUND
Because the symptoms of premenstrual dysphoric disorder (PMDD) are limited to the luteal phase of the menstrual cycle, the potential benefit of luteal-phase dosing has been hypothesized.


OBJECTIVE
This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial evaluated the efficacy and tolerability of enteric-coated fluoxetine 90 mg given once or twice during the luteal phase for the treatment of PMDD.


METHODS
Study drug was given 14 and 7 days before expected menses during the luteal phase of 3 menstrual cycles. After a screening period and single-blind placebo lead-in period, eligible women were randomized to I of 3 treatment groups: enteric-coated fluoxetine 90 mg on both days (LPWDx2); placebo 14 days before menses and enteric-coated fluoxetine 90 mg 7 days before menses (LPWDx1); or placebo on both days (PLC). The primary efficacy measure was change from baseline in mean luteal-phase scores on the Daily Record of Severity of Problems (DRSP). Secondary efficacy measures included scores on the Rating Scale for Premenstrual Tension Syndrome, Clinician-Rated (PMTS-C); the Clinical Global Impression (CGI)-Severity scale; and the Patient Global Impression (PGI)-Improvement scale. Quality of life was assessed using the Sheehan Disability Scale.


RESULTS
Two hundred fifty-seven women were randomized to treatment. At the end of the study, the LPWDx2 group had statistically significant improvements in DRSP total, DRSP mood subtotal, DRSP social functioning subtotal, PMTS-C, CGI-Severity, PGI-Improvement, and Sheehan Disability Scale work and family life scores compared with LPWDx1 and PLC (each measure, P < 0.05). There was also a statistically significant improvement in the score on the social life section of the Sheehan Disability Scale with LPWDx2 compared with PLC (P = 0.037). Across all treatment groups, 5 patients discontinued due to nonserious adverse events. Rates of discontinuation for any reason did not differ between the 3 treatment groups.


CONCLUSIONS
The findings of this study support the efficacy and tolerability of enteric-coated fluoxetine 90 mg given twice during the luteal phase of the menstrual cycle for the treatment of PMDD.
Miner
Cherri
C
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. miner_cherri@lilly.com
Brown
Eileen
E
McCray
Susan
S
Gonzales
Jill
J
Wohlreich
Madelaine
M
D000293:Adolescent; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005498:Follicular Phase / Q000523:psychology; D006801:Humans; D008183:Luteal Phase / Q000502:physiology* / Q000523:psychology*; D008875:Middle Aged; D011293:Premenstrual Syndrome / Q000188:drug therapy* / Q000523:psychology*; D011569:Psychiatric Status Rating Scales; D013608:Tablets, Enteric-Coated; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D013608:Tablets, Enteric-Coated; D005473:Fluoxetine