Published online Nov 19, 2025. doi: 10.5498/wjp.v15.i11.111807
Revised: July 27, 2025
Accepted: August 26, 2025
Published online: November 19, 2025
Processing time: 117 Days and 17.2 Hours
Sleep disturbances are a prominent feature of bipolar disorder (BD) and often persist even in remission, thereby contributing to poor clinical outcomes. Despite the widespread use of lithium and valproic acid as mood stabilizers, their effects on sleep quality have not been examined in adequate detail.
To evaluate and compare the effects of lithium and valproic acid on sleep quality in BD patients under remission.
A total of 130 patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for BD in remission were included in this cross-sectional study. The participants were receiving either lithium (n = 78), or valproic acid (n = 52), for a minimum of six months either alone or in combination with antipsychotics. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Comparative analyses between the lithium and valproic acid groups were conducted using independent t-tests, χ2 tests, and ANCOVA, adjusting for key variables such as age, sex, and body mass index.
Both groups demonstrated poor sleep quality, with the mean PSQI scores above the clinical threshold of 5. Patients in the lithium group exhibited significantly better habitual sleep efficiency (lithium: 0.47 ± 0.65, valproic acid: 0.78 ± 0.87, P = 0.009) and fewer sleep disturbances (lithium: 1.26 ± 0.57, valproic acid: 1.61 ± 0.84, P = 0.005). Other sleep parameters, including total sleep duration (P = 0.082) and sleep latency (P = 0.625), did not differ significantly.
Patients in the lithium group showed significantly better habitual sleep efficiency and fewer sleep disturbances compared to those receiving valproic acid, although other sleep parameters did not differ. These findings suggest a potential advantage of lithium in certain aspects of sleep quality in BD patients under remission. Future studies using objective sleep measures and longitudinal designs are warranted to confirm these findings.
Core Tip: This study explored how two commonly used mood stabilizers, lithium and valproic acid, affect sleep quality in patients with bipolar disorder (BD) during remission. Although overall sleep quality was poor in both groups, patients treated with lithium showed significantly better sleep efficiency and fewer sleep disturbances compared to those receiving valproic acid. These findings highlight the potential advantage of lithium in promoting more stable and restorative sleep in BD. Given the critical role of sleep in the long-term course and relapse risk of BD, our results suggest that sleep-related outcomes should be considered when selecting maintenance treatments. Further studies using objective sleep measures and longitudinal designs are needed to build on these findings.