Clinical trial NCT01799733: Alternative Treatments for Premenstrual Dysphoric Disorder
Official title: Alternative Treatments for Premenstrual Dysphoric Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Premenstrual Dysphoric Disorder
Keywords: Premenstrual Dysphoric Disorder
Women
Depression
Light therapy
Wake therapy
Phase
Chronobiology
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2013-02-27
Enrollment: 43
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 40 women with Premenstrual Dysphoric Disorder ages 18-45 will be randomized to a cross-over design contrasting one night of Late Wake Therapy followed by 7 days of morning Bright-White Light (LWT+AM BWL) vs. one night of Early Wake Therapy followed by evening Bright-White Light (EWT+PM BWL) administered in the luteal phase of two separate menstrual cycles, with one month of no intervention (washout) between treatments to prevent carry-over effects. Treatment will be preceded by 2 evaluation months to determine diagnosis and collect baseline mood, sleep, actigraphy and endocrine measures. To lessen the patient's burden, the 1-night EWT or LWT and the following 7-day BWL interventions will be conducted at home, given at a fixed point in each menstrual cycle, from the day of mid-cycle LH surge to 7 after the LH surge.
Primary purpose: TREATMENT

Brief summary: The primary aim of this study is to examine the effects of co-administered wake therapy followed by light treatment on mood, and secondarily on circadian rhythms, to test the hypothesis that critically-timed chronotherapy improves mood by correcting phase disturbances in melatonin and sleep in women with Premenstrual Dysphoric Disorder.

Detailed description: The design is a randomized cross-over contrasting Late Wake Therapy plus morning bright light (LWT+Am BWL)vs. Early Wake Therapy plus evening bright light (EWT+PM BWL)administered in the luteal phase of two separate menstrual cycles, and preceded by 2 evaluation months. To lessen the patient's burden, the 1-night EWT or LWT and the following 7-day BWL interventions will be conducted at home, given at a fixed point in each menstrual cycle, from day 1 to 7 after the mid-cycle luteinizing hormone(LH) surge (ovulation). We anticipate that LWT+7 days of AM BWL (vs. EWT+PM BWL) will produce much greater mood benefits and larger physiological responses, than the one-time light pulses used in our earlier phase-shift studies.

Eligibility criteria: Inclusion Criteria:

* Age: 18-45 years.
* Women with regular ovulatory menstrual cycles 26-32 days in length (for at least the previous six months).
* A history of a depressive (but not bipolar) mood disorder, but not an ongoing episode (symptom free for the last 12 months).
* Patients must meet DSM-IV criteria for Premenstrual Dysphoric Disorder (that includes irritability).
* Objective ratings: mean HRSD \< 7 for follicular phase (day 5-10 of cycle after menses); mean HRSD \> 14 for premenstrual (luteal) phase (6 days prior to onset of menses onward).
* Subjective ratings: mean Beck Depression Inventory \< 5 follicular phase; \> 10 premenstrual (luteal) phase, or
* Daily ratings: minimal symptoms (mean less than 50 on 100mm scale) follicular phase; at least a 30% increase in mean affective symptom ratings, premenstrual (luteal) phase.
* By clinical assessment and ratings, the patient has reported a history (for at least the last six months) of recurrent, moderate to severe premenstrual mood symptoms that impair some aspect of social or occupational functioning and that remit within a few days after the onset of menses. This pattern is prospectively documented with subjective and objective ratings over a 2-3 month interval. Patients must demonstrate a consistency of symptoms and a long enough duration of symptoms (7-10 days) to allow for study.
* Subjects willing to endure the rigors of a long-term (up to 6 months) research study.

Exclusion Criteria:

* Subjects with significant medical illness including hepatic (abnormal liver function tests), neurological, renal, cardiac, pulmonary, hematologic, gastrointestinal, or metabolic disorders.
* Subjects who are lactating, are within 6 months postpartum, or have an irregular sleep- wake cycle, e.g., from having very young children in the home.
* Subjects who are using hormonal contraception (within six months prior to the study).
* Subjects using other medication within one month of initiating the study or anytime during the study.
* Subjects with significant psychiatric disorder (schizophrenia, bipolar disorder, anxiety disorders, eating disorders, personality disorders, sleep disorders). An ongoing major depressive episode within the last year is reason for exclusion, although a previous history of a depressive episode is not (using DSM-IV diagnostic criteria for a major depressive episode).
* Subjects with a recent history (within the past year) of drug or alcohol abuse.
* Subjects with clinically significant abnormal laboratory values.
* Subjects with irregular menstrual cycles (cycle lengths vary greater than 3 days).
* Subjects unlikely to cooperate with the requirements of the study.
* Subjects needing frequent or continuous use of any medication, including nicotine (\> 5 cigarettes daily).
* Subjects whose prospective ratings do not show cyclic variation in association with the menstrual cycle (as per inclusion criteria).
* Subjects with an irregular sleep schedule, extreme chronotypes or a sleep-wake cycle that does not correspond to the environmental light-dark cycle (e.g., subjects within 2 weeks of transmeridian travel, night shift workers, or those with significant advanced or delayed sleep phase syndromes). To enhance precision of the timing of the light stimulus on circadian phase (temporal resolution), we will exclude women with habitual sleep onset times after midnight or wake times after 9 am.

Primary outcomes:
measure: Treatment-Related Changes from baseline in mood ratings
timeFrame: baseline (month 2) and 1-2 days post intervention (months 3,5)
measure: Treatment-Related Changes from Baseline in Urinary 6-sulfatoxymelatonin (6-SMT)
timeFrame: baseline (month 2) and 1-2 days post intervention (months 3,5)
measure: Treatment-related changes in objective and subjective sleep measures
timeFrame: baseline (month 2) and 1-2 days post intervention (months 3,5)
Secondary outcomes:
measure: Effects of expectation, morningness/eveningness and seasonality on primary outcome measures
timeFrame: baseline
measure: Treatment-related changes from baseline in reproductive hormones
timeFrame: baseline (month 2) and 1-2 days post intervention (months 3,5)
measure: Subjective visual analog scale-based global assessment of treatment effectiveness
timeFrame: 1-2 days post second intervention (month 5)
measure: Subjective assessment of side effects to treatment
timeFrame: 1-2 days post intervention (months 3,5)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UCSD Medical Center, Hillcrest
state: California
Study officials:
affiliation: University of California, San Diego
name: Barbara L Parry, M.D.
role: PRINCIPAL_INVESTIGATOR
References: