Alternative Treatments for Premenstrual Dysphoric Disorder

NCT01799733 | Completed DMC

• 1 other identifier: 1R01AT007169-01A1
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

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.

Conditions

Premenstrual Dysphoric Disorder

Keywords

Premenstrual Dysphoric Disorder; Women; Depression; Light therapy; Wake therapy; Phase; Chronobiology

Outcome Measures

Primary Outcomes (3)

• Treatment-Related Changes from baseline in mood ratings

  Mood ratings include Hamilton Rating Scale for Depression (HRSD), Beck Depression Inventory (BDI), atypical depression symptoms as part of the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders version (SIGH-SAD), Beck Anxiety Inventory (BAI), mania ratings, the Psychological General Well-Being Index (PGWI) and daily mood self-ratings (DMR) that include core PMDD symptoms of anxiety and irritability as required during diagnostic evaluation, before, during and after each wake and light intervention at the same time of day (between 15:00-17:00 h). To assess more acute effects on mood that may occur more rapidly during the wake interventions, subjects will complete DMRs twice daily beginning the evening before the wake therapy intervention and continuing until the morning after the recovery night of sleep.

  baseline (month 2) and 1-2 days post intervention (months 3,5)

• Treatment-Related Changes from Baseline in Urinary 6-sulfatoxymelatonin (6-SMT)

  6-SMT is a principal melatonin metabolite that is abundant in urine, well correlated with plasma melatonin, and serves as an excellent marker for circadian phase response.

  baseline (month 2) and 1-2 days post intervention (months 3,5)

• Treatment-related changes in objective and subjective sleep measures

  Using actigraphy, we will obtain objective measures of the sleep/wake cycle to ensure appropriate sleep/wake times during wake therapy, and during the light interventions as it is an important biological rhythm with which to compare the intervention-induced melatonin rhythm changes. To assess subjective sleep quality, we will use the Pittsburgh Sleep Quality Index (PSQI) and a visual analogue scale.

  baseline (month 2) and 1-2 days post intervention (months 3,5)

Secondary Outcomes (4)

• Effects of expectation, morningness/eveningness and seasonality on primary outcome measures

  baseline

• Treatment-related changes from baseline in reproductive hormones

  baseline (month 2) and 1-2 days post intervention (months 3,5)

• Subjective visual analog scale-based global assessment of treatment effectiveness

  1-2 days post second intervention (month 5)

• Subjective assessment of side effects to treatment

  1-2 days post intervention (months 3,5)

Study Arms (2)

LWT+AM BWL

ACTIVE COMPARATOR

Late-wake therapy in combination with morning bright white light

Other: LWT+AM BWL

EWT+PM BWL

PLACEBO COMPARATOR

Early-wake therapy in combination with evening bright white light

Other: EWT+PM BWL

Interventions

LWT+AM BWL OTHER

One night of late wake therapy (LWT)(sleep 21:00-01:00 h, followed by wakefulness) plus 7 days of morning bright white light (AM BWL)(light-emitting diode-LED administered for 60 minutes, starting within 30 minutes of habitual wake time)

LWT+AM BWL

EWT+PM BWL OTHER

One night of early wake therapy (EWT) (wakefulness until 03:00 h, then sleep 03:00-07:00 h) plus 7 nights of evening bright white light (PM BWL)(light-emitting diode-LED administered 90 minutes before habitual sleep onset, for 60 minutes)

EWT+PM BWL

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 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 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.

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

UCSD Medical Center, Hillcrest

San Diego, California, 92103, United States

Location

Related Publications (1)

• Parry BL, Meliska CJ, Martinez LF, Lopez AM, Sorenson DL, Dawes SE, Elliott JA, Hauger RL. A 1-week sleep and light intervention improves mood in premenstrual dysphoric disorder in association with shifting melatonin offset time earlier. Arch Womens Ment Health. 2023 Feb;26(1):29-37. doi: 10.1007/s00737-022-01283-z. Epub 2022 Dec 15.

  PMID: 36520251 DERIVED

MeSH Terms

Conditions

Premenstrual Dysphoric Disorder; Depression

Condition Hierarchy (Ancestors)

Premenstrual Syndrome; Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Barbara L Parry, M.D.

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The principal investigator and clinical rater will remain blind to treatment condition until completion or discontinuation of participant from study. As patients will be coded, one statistician and technician and supervisor running assays also will be blind to patient name and treatment condition. Members of the Data Safety Monitoring Committee will review records in which patient names are coded, unless the code needs to be broken in the event of an adverse outcome. All other lab personnel will not be blind to treatment as the study coordinator and research associate prepare patient equipment and instruct patients on proper completion of the treatment protocol, the data manager and quality assurance officer enter all data into the database (including treatment condition). Due to the nature of the treatment (sleep, light intervention), patients will not be blind to condition.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor IR

Model Details: 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.

Study Record Dates

• First Submitted: February 25, 2013
• First Posted: February 27, 2013
• Study Start: June 18, 2013
• Primary Completion: May 10, 2018
• Study Completion: July 3, 2018
• Last Updated: February 4, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)