Research Article| Volume 24, ISSUE 3, P417-433, March 2002

Weekly luteal-phase dosing with enteric-coated fluoxetine 90 mg in premenstrual dysphoric disorder: A randomized, double-blind, placebo-controlled clinical trial

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      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 1 of 3 treatment groups: enteric-coated fluoxetine 90 mg on both days (LPWD×2); placebo 14 days before menses and enteric-coated fluoxetine 90 mg 7 days before menses (LPWD×1); 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 LPWD×2 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 LPWD×1 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 LPWD×2 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.
      Conclusion: 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.


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        • Johnson SR
        The epidemiology and social impact of premenstrual symptoms.
        Clin Obstet Gynecol. 1987; 30: 367-376
        • Rivera-Tovar AD
        • Frank E
        Late luteal phase dysphoric disorder in young women.
        Am J Psychiatry. 1990; 147: 1634-1636
        • Ramcharan S
        • Love EJ
        • Fick GH
        • Goldfien A
        The epidemiology of premenstrual symptoms in a population-based sample of 2650 urban women: Attributable risk and risk factors.
        J Clin Epidemiol. 1992; 45: 377-392
        • American Psychiatric Association
        Fourth Edition. Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association, Washington, DC1994
        • Endicott J
        • Amsterdam J
        • Eriksson E
        • et al.
        Is premenstrual dysphoric disorder a distinct clinical disorder?.
        J Women's Health. 1999; 8: 663-679
        • Yonkers KA
        • Halbreich U
        • Freeman E
        • et al.
        • Sertraline Premenstrual Dysphoric Collaborative Study Group
        Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. A randomized controlled trial.
        JAMA. 1997; 278: 983-988
        • Steiner M
        • Steinberg S
        • Stewart D
        • et al.
        • Canadian Fluoxetine/Premenstrual Dysphoria Collaborative Study Group
        Fluoxetine in the treatment of premenstrual dysphoria.
        N Engl J Med. 1995; 332: 1529-1534
        • Su TP
        • Schmidt PJ
        • Danaceau MA
        • et al.
        Fluoxetine in the treatment of premenstrual dysphoria.
        Neuropsychopharmacology. 1997; 16: 346-356
        • Pearlstein TB
        • Stone AB
        Long-term fluoxetine treatment of late luteal phase dysphoric disorder.
        J Clin Psychiatry. 1994; 55: 332-335
        • Freeman EW
        • Rickels K
        • Arredondo E
        • et al.
        Full- or half-cycle treatment of severe premenstrual syndrome with a serotonergic antidepressant.
        J Clin Psychopharmacol. 1999; 19: 3-8
      1. FDA approves fluoxetine to treat premenstrual dysphoric disorder.
        FDA Talk Paper T00-31. July 6, 2000; (Available at: Accessed November 6, 2001)
        • Steiner M
        • Korzekwa M
        • Lamont J
        • Wilkins A
        Intermittent fluoxetine dosing in the treatment of women with premenstrual dysphoria.
        Psychopharmacol Bull. 1997; 33: 771-774
        • Judge R
        • Brown E
        • Miner C
        • Dillon J
        Intermittent fluoxetine dosing in premenstrual dysphoric disorder.
        World J Biol Psychiatry. 2001; 2 (Abstract): 204S
        • Sundblad C
        • Wikander I
        • Andersch B
        • Eriksson E
        A naturalistic study of paroxetine in premenstrual syndrome: Efficacy and side-effects during ten cycles of treatment.
        Eur Neuropsychopharmacol. 1997; 7: 201-206
        • Wikander I
        • Sundblad C
        • Andersch B
        • et al.
        Citalopram in premenstrual dysphoria: Is intermittent treatment during luteal phases more effective than continuous medication throughout the menstrual cycle?.
        J Clin Psychopharmacol. 1998; 18: 390-398
        • Jermain DM
        • Preece CK
        • Sykes RL
        • et al.
        Luteal phase sertraline treatment for premenstrual dysphoric disorder. Results of a double-blind, placebo-controlled, crossover study.
        Arch Fam Med. 1999; 8: 328-332
        • Young SA
        • Hurt PH
        • Benedek DM
        • Howard RS
        Treatment of premenstrual dysphoric disorder with sertraline during the luteal phase: A randomized, double-blind, placebo-controlled crossover trial.
        J Clin Psychiatry. 1998; 59: 76-80
        • Halbreich U
        • Smoller JW
        Intermittent luteal phase sertraline treatment of dysphoric premenstrual syndrome.
        J Clin Psychiatry. 1997; 58: 399-402
        • Schmidt ME
        • Fava M
        • Robinson JM
        • Judge R
        The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder.
        J Clin Psychiatry. 2000; 61: 851-857
        • Endicott J
        • Harrison W
        Daily rating of severity of problems form. Dept of Research Assessment and Training, NY State Psychiatric Institute, New York1990
        • Steiner M
        • Streiner DL
        • Steinberg S
        • et al.
        The measurement of premenstrual mood symptoms.
        J Affective Disord. 1999; 53: 269-273
      2. Guy W ECDEU Assessment Manual for Psychopharmacology, Revised. National Institute of Mental Health, Rockville, MD1976: 76-338
        • Steiner M
        • Haskett RF
        • Carroll BJ
        Premenstrual tension syndrome: The development of research diagnostic criteria and new rating scales.
        Acta Psychiatr Scand. 1980; 62: 177-190
        • Leon AC
        • Olfson M
        • Portera L
        • et al.
        Assessing psychiatric impairment in primary care with the Sheehan Disability Scale.
        Int J Psychiatry Med. 1997; 27: 93-105
        • Montgomery DC
        Design and Analysis of Experiments. John Wiley & Sons, New York1991: 50-94
        • Steiner M
        • Romano SJ
        • Babcock S
        • et al.
        The efficacy of fluoxetine in improving physical symptoms associated with premenstrual dysphoric disorder.
        Br J Obstet Gynaecol. 2001; 108: 462-468