Sleep-wake disturbance in interepisode bipolar disorder and high-risk individuals: a systematic review and meta-analysis.

Over the past decade, researchers have shifted focus from the manic and depressive episodes to the interepisode period in the study of sleep-wake disturbance in bipolar disorder. The objective of this systematic review was to compile and synthesize studies that employed sleep diary, actigraphy, polysomnography, and questionnaires to compare sleep-wake patterns in people with interepisode bipolar disorder or high-risk individuals vs. normal controls and/or people with primary insomnia. We searched key databases until June 2013. Our search identified 21 eligible studies, yielding 24 sleep-wake variables. A total of 531 people with interepisode bipolar disorder, 157 high-risk individuals, 678 normal controls and 67 adults with primary insomnia were evaluated. Using a random-effects model, our analyses suggest that adults with interepisode bipolar disorder appear worse than normal controls in most variables and comparable to adults with primary insomnia in certain aspects. Sleep onset latency, wake after sleep onset, and variability of sleep-wake variables were most consistently impaired in interepisode bipolar disorder. In comparison with controls, high-risk individuals were found to have higher variability in sleep efficiency and lower relative amplitude. The findings provide a foundation for the search for candidate endophenotypes and the development of novel interventions for bipolar disorder.