Sleep in Bipolar Disorder: A Systematic Review and Meta-Analysis of Case Control Drug Free Patients

Background/Objectives A systematic review and meta-analysis of polysomnographic sleep pa-rameters in bipolar disorder was conducted using articles identified through searches of major databases from inception to May 5, 2026. Methods: One hundred eight studies were identified in the systematic review. Forty-three case-control studies with 670 bipolar patients, 520 healthy con-trols and 280 unipolar depression patients were eligible for the meta-analyses. Total sleep time, sleep onset latency, sleep efficiency, wake after sleep onset, REM time and percentage, REM la-tency, REM density, stage 1, 2, time and percentage, slow wave sleep (DELTA) time and percent-age, of drug free patients with bipolar disorder were compared with case-control data of healthy controls and drug free patients with unipolar depression. The primary outcome was the standard mean difference. Data were fitted with a random-effects model. Publication bias assessment was checked by Egger's Regression and funnel plot asymmetry Results: Total sleep time and sleep ef-ficiency were reduced in both manic and depressive drug-free bipolar patients compared to healthy controls. Delta sleep time and percentage were reduced only in the depressive patients, whereas the manic patients showed decreased stage 2 sleep time, reduced REM sleep time, shortened REM la-tency and increased REM density. Drug free patients with unipolar depression showed reduced total sleep time and increased REM density compared to drug free patients with bipolar depression. Drug treated bipolar patients showed no differences compared to healthy controls, except for reduced % REM, increased REM latency and increased REM density. Conclusions: The results confirm the presence of sleep alterations in bipolar disorder, although sleep duration is reduced in both manic and depressive patients, reduced delta sleep in depressive patients and increased activity/pressure of REM in manic patients appear to characterize the two phases of the illness. Altered monoam-inergic activity during the depressive phase and increased cholinergic activity during the manic phase, might possibly be responsible for the sleep alterations also contributing to the mood changes and switch mechanisms.