Luteal Phase Sertraline and PMDD

Abstract & Commentary

Synopsis: Sertraline was significantly more effective than placebo when taken during the luteal phase for PMDD.

Source: Halreich U, et al. Obstet Gynecol. 2002;100: 1219-29.

In a busy office practice of obstetrics and gynecology, one of the clinical presentations that can bring to a grinding halt even a smoothly running schedule is severe premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD). A severe subtype of premenstrual syndrome, PMDD is a specifically defined condition listed in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV).

This group of well-known researchers in this field of study present data from 14 psychiatric and gynecologic outpatient clinics in the United States and Canada. The study was well designed, screening out inappropriate subjects on both retrospective and prospective bases. This makes such a study that much more significant, as the literature is filled with poorly designed studies with unacceptable inclusion/exclusion criteria.

Appropriate subjects were randomized in a double-blinded fashion, to 3 months of luteal phase therapy with either sertraline or placebo. The initial dose was sertraline 50 mg per day (or the placebo equivalent) during the luteal phase. The dose could be increased to 100 mg (or the comparable placebo) if the patient’s response were deemed inadequate by Halreich and colleagues. Two hundred eighty-one patients entered the study. Superiority of sertraline over placebo was seen by the end of the first treatment cycle and persisted throughout all 3 cycles of double-blind therapy. Categories of improvement included mood and behavioral measurements (depressive symptoms, anxiety, and irritability), cognitive functioning/concentration, and quality of life (social functioning, interference with hobbies, and productivity). Not only was the medication effective, but it was also well tolerated, with less than 8% discontinuing treatment because of adverse events. Not surprisingly, physical symptoms were not improved.

Comment by Frank W. Ling, MD

Although funded by industry, this study need not be viewed with skepticism and/or cynicism. Halreich et al have a track record of quality research, and the size of the study, as well as the strict entry criteria, make for good science. This latest piece of the PMDD/severe PMS treatment story provides the clinician another useful tool in dealing with a challenging scenario.

The astute practitioner will not view this as the panacea for the wide range of patients who present with premenstrual symptoms. Instead, the use of sertraline or another serotonergic agent will be find its proper role in each clinician’s own "algorithm" in treating PMS/PMDD. Since the current state of knowledge of the underlying pathophysiology suggests that there is a normal hypothalamic/pituitary/ovarian axis that triggers an abnormal serotonin response, many treatments proffered in the past have now fallen out of favor. Given the literature suggesting benefit of behavioral and/or pharmacologic intervention, a stair-step approach is often found to be useful:

Step 1 (Behavioral): validation of symptoms to the patient; low-fat, vegetarian diet; elimination of caffeine; reduction of salt intake; prospective monitoring of symptoms;

Step 2 (Dietary supplements and nonprescription medications): calcium carbonate, chasteberry extract, pyridoxine (vitamin B6), and nonsteroidal anti-inflammatories;

Step 3 (Prescription medications): hormonal (some oral contraceptives, danazol, gonadotropin-releasing hormone analogues) and selective serotonin reuptake inhibitors (SSRIs).

With previous publications demonstrating that other SSRIs also can be used effectively during luteal phase dosing, sertraline can logically take its place as a potential first choice among a group of comparable medications. With the use of luteal phase dosing, patients and their physicians are potentially able to see a rapid response to treatment. In addition, the concern over taking a pill every day that is often voiced by patients can be avoided.

Differentiating this condition from true depression remains a critical decision. Although it’s certainly convenient that antidepressants are also effective for PMDD, it remains of paramount importance to determine what the condition is. Prescribing sertraline during the luteal phase as reported here should be reserved for those patients whose diagnosis and symptom severity warrant its use. 

Dr. Ling is UT Medical Group Professor and Chair, Department of Obstetrics and Gynecology, University of Tennessee Health Science Center, Memphis, TN.