Premenstrual Dysphoric Disorder

What historically has been referred to as premenstrual syndrome is now defined as premenstrual dysphoric disorder (PMDD) in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV).²³ This illness occurs during the premenstrual, or late luteal, phase of the menstrual cycle; symptoms remit during the beginning of the follicular phase. In psychiatry, PMDD is one of the few disorders in which both the precipitating and the remitting influences are linked to one physiologic process.

Premenstrual dysphoric disorder is classified as a mood disorder, "Depressive Disorder, Not Otherwise Specified," in the DSM-IV. Because of political controversy surrounding the inclusion of this disorder in the DSM-IV text, its criteria are listed in Appendix B, as an area needing further research.²³ Three factors are involved in making the diagnosis of PMDD. First, the symptoms must be primarily related to mood. Currently, PMDD symptoms are listed in the DSM-IV in order of their frequency of occurrence. After pooling the ratings from several centers across the United States, the most frequently reported symptom was depression.²⁴ Second, symptom severity has to be problematic enough in the woman's personal, social, work, or school history to interfere with functioning; this criterion is also used for other psychiatric disorders. Third, the symptoms need to be documented in relationship to the timing of the menstrual cycle; they must occur premenstrually and remit shortly after the onset of menses. This cyclic pattern needs to be documented by daily mood ratings.

DeJong and colleagues²⁵ examined women who reported premenstrual symptoms. Of those women who completed daily mood ratings, 88% were diagnosed with a psychiatric disorder; the majority had a major depressive disorder. This study reflects the necessity for careful prospective screening as to the timing and severity of symptoms for women presenting with premenstrual complaints.

Role of the Serotonin System

The role of the serotonin system in discriminating PMDD patients from normal control subjects is well-supported in the literature,²⁶ and it explains the efficacy of the selective serotonin reuptake inhibitors (SSRIs) in treating this disorder.^27,28 Whether by platelet serotonin uptake or imipramine binding studies, PMDD versus healthy comparison subjects have lower serotonergic function.²⁶ In a multicenter Canadian trial, Steiner and colleagues²⁸ examined the clinical efficacy of fluoxetine at 20 mg per day versus 60 mg per day throughout the menstrual cycle in women with PMDD. The 20-mg dosage was as effective as the 60-mg dosage, with fewer side effects. Both dosages were more effective than the placebo. A multicenter sertraline trial²⁷ also showed significantly greater efficacy of active drug versus placebo. Ongoing studies are addressing whether these antidepressant medications can be effective when administered only in the luteal phase;²⁹ many women do not want a chronic treatment for a periodic illness. Additionally, side effects from these medications may still be problematic, which can lead to noncompliance.

Sleep Deprivation

For this reason, our laboratory has been investigating nonpharmacologic treatment strategies for PMDD. Based on circadian theories, we utilize sleep deprivation and phototherapy.^30-33 Gender differences in the hormonal modulation of the circadian system have been well-documented. In animal studies, estrogen has been found to shorten the free-running period (the length of the sleep/wake cycle [humans] or rest/activity cycle [animals] in temporal isolation [non-entrained conditions]), which is the length of day/night cycles in temporal isolation studies.^34,35 It also advances the timing of activity onset and helps to maintain internal phase (timing) relationships between different circadian components. In ovariectomized hamsters, circadian rhythms become desynchronized. When estrogen is reinstituted, the synchronous effect is regained.³⁶
Both estradiol and progesterone affect the development of the part of the brain that regulates circadian rhythms, the suprachiasmatic nucleus.³⁷ Estradiol and progesterone also affect the response to light that controls circadian rhythms.^38,39 In human studies, females continue to demonstrate shorter free-running periods in temporal isolation.^40,41 Desynchronization tends to occur at certain endocrine phases of the menstrual cycle.⁴² Circadian disturbances in melatonin amplitude and phase also occur during specific menstrual cycle phases.⁴³

These circadian rhythms can be realigned by using light to change the sleep cycle, or the underlying circadian clock. Sleep deprivation can improve mood in one day for patients with major depression;⁴⁴ however, they may relapse after returning to sleep. Patients with premenstrual depression improve after a night of sleep deprivation but do not relapse after a night of recovery sleep.^30,33

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