Pilot Study of the Effects of Circadian Rhythms on the Treatment of Bipolar I Depression.

Rhythmicity as a Moderator of Treatment Outcomes of Bipolar I Depression -Pilot Study

The objective of this pilot study is to test the feasibility of a larger planned trial. The objective of this larger trial will be to determine the extent to which aspects of circadian rhythmicity, including, sleep/wake rhythms, daily social routines (i.e., social rhythms), circadian type (morningness/eveningness), endogenous circadian rhythms and polymorphisms associated with altered circadian function in specific genes (namely, CLOCK, Period 2 and Period 3) moderate treatment response in bipolar disorder.

This study is a small scale pilot study which will be used to support a larger trial. The major aims of the larger study are to determine the extent to which aspects of circadian rhythmicity, including, sleep/wake rhythms, daily social routines (i.e., social rhythms), circadian type (morningness/eveningness), endogenous circadian rhythms and polymorphisms associated with altered circadian function in specific genes (namely, CLOCK, Period 2 and Period 3) moderate treatment response in bipolar disorder.

The overarching aim of the study is to clarify the nature of rhythm abnormalities in bipolar disorder and, especially, their relation to clinical state. We propose to do this in the context of a randomized intervention protocol in which half of the subjects will receive a treatment aimed at rhythm regularization. We expect to study individuals with a range of circadian and sleep-wake abnormalities, social rhythm disturbances, and circadian type and to examine the extent to which these parameters predict subjects' clinical outcomes. Since one half of the subjects will receive IPSRT as part of their treatment regimen (with increasing regularity of social routines as a goal of treatment), we will be able to examine the extent to which changes in social rhythm regularity and sleep quality are associated with clinical and functional improvement and whether these outcomes are mediated by changes in endogenous circadian rhythms.

Inclusion Criteria:

1. Age 18 to 60 years
2. Able to give basic informed consent
3. Meets DSM-IV criteria for current acute episode of bipolar I depression
4. Women of childbearing potential must agree to use a doctor-approved birth control throughout participation in the study
5. Hamilton Depression Rating Scale (17-item) score > or equal to 15
6. Hamilton Depression Rating Scale (17-item) item 1 score > or equal to 2
7. Young Mania Rating Scale score < or equal to 12

Exclusion Criteria:

1. Unwilling or unable to comply with study requirements (i.e., complete forms, attend scheduled evaluations)
2. Not competent to provide informed consent in the opinion of the investigator
3. Rapid cycling (4 or more episodes per year) bipolar I disorder
4. Present treatment for index depressive episode with lithium or quetiapine unless does or serum level are deemed inadequate
5. Lithium intolerance or a past failed adequate trial of Lithium
6. Quetiapine intolerance or a past failed adequate trial of quetiapine
7. Presence of schizophrenia, schizoaffective, antisocial or pervasive developmental disorder, psychotic disorder, current substance dependence, and organic mental disorder
8. Axis II borderline disorder
9. Mini-Mental State Examination score <24
10. Current alcohol and illicit substance abuse
11. Women who are currently pregnant, planning to become pregnant or currently breast-feeding