Lithium and valproic acid in bipolar disorder: Beyond mood stabilization, the overlooked role of sleep

Abstract

Sleep is a critical yet often underestimated physiological parameter in psychiatric disorders. In their article, Gokcay et al examined sleep quality in bipolar disorder patients treated with lithium or valproic acid, showing lithium’s advantage in habitual sleep efficiency and reduced disturbances. While this study provides valuable data in a chronic and clinically challenging cohort, reliance solely on self-reported sleep measures remains a limitation. Polysomnography, although the gold standard, is not always practical; therefore, actigraphy and wearable technologies represent feasible alternatives to capture objective sleep patterns. This letter emphasizes the importance of integrating objective, scalable technologies and pharmacological monitoring into longitudinal designs to clarify whether improvements in sleep translate into better clinical outcomes and reduced relapse risk in bipolar disorder.

Key Words: Mood stabilizers; Sleep; Wearable technologies; Bipolar disorder; Lithium; Valproate

Core Tip: This letter emphasizes the importance of evaluating sleep as a central physiological parameter in bipolar disorder. While the original study demonstrated lithium's advantage over valproic acid in sleep quality. It is highlighted that reliance solely on self-reported scales is a limitation. Wearable technologies and actigraphy offer objective, scalable alternatives to polysomnography. Future studies should integrate serum drug-level monitoring and adjunctive antipsychotic data into longitudinal designs to clarify how mood stabilizers influence sleep and to advance personalized treatment strategies in bipolar disorder.

TO THE EDITOR

The article by Gokcay et al[1] entitled “Sleep quality in bipolar disorder: A comparative study of treatment with lithium and valproic acid” was read with great interest. The authors are to be congratulated for investigating the impact of mood stabilizers on sleep in a sample of patients with relatively long illness duration and high episode burden, features that render their cohort particularly valuable for understanding chronic and severe cases of bipolar disorder. The study makes a significant contribution to the growing body of literature highlighting sleep as a crucial physiological parameter in psychiatric disorders. Sleep disturbances not only persist during remission but also influence the course of illness, treatment response, and risk of relapse[2,3]. In this context, evaluating sleep should not be considered a secondary outcome but rather a central component of treatment strategies in bipolar disorder, given its strong predictive value for relapse and functional impairment.

First, sleep was assessed exclusively by self-report using the Pittsburgh Sleep Quality Index. While subjective scales capture patients’ perspectives, they may not accurately reflect underlying sleep architecture. Polysomnography remains the gold standard for sleep evaluation; however, it is often costly and impractical for large-scale clinical research. Thus, incorporating more feasible and scalable methods, such as wearable technologies and actigraphy, could provide objective, ecologically valid insights into sleep patterns in individuals with bipolar disorder[4,5]. Integrating such tools into clinical research may also enhance patient engagement and yield longitudinal, real-world data otherwise difficult to obtain.

Second, psychotropic medications beyond lithium and valproic acid, including antipsychotics used as adjunctive agents, have profound effects on sleep continuity and architecture[6]. In addition, serum levels of mood stabilizers may influence neurophysiological sleep processes, yet pharmacokinetic monitoring was not integrated into the study. Future designs should therefore stratify patients by adjunctive antipsychotic use and, where possible, include therapeutic drug monitoring alongside objective sleep measures. Such approaches would clarify drug-specific contributions to sleep outcomes. A combined design using wearable-based sleep metrics, drug plasma-level monitoring, and stratification by adjunctive treatment could clarify drug-specific contributions to sleep physiology in bipolar disorder.

Finally, while the cross-sectional nature of the study limits causal inference, the results highlight lithium’s potential advantage in stabilizing sleep efficiency and reducing disturbances. Longitudinal studies that combine actigraphy or wearable monitoring with systematic medication profiling could determine whether these sleep-related benefits translate into lower relapse rates and improved functional trajectories. Such evidence could further support personalized medicine approaches, where treatment selection prioritizes both mood stabilization and restoration of healthy sleep.

In conclusion, Gokcay et al[1] provide important evidence suggesting that lithium may confer unique benefits for sleep regulation in bipolar disorder. I recommend that future investigations integrate objective technologies, account for pharmacological variables, and adopt longitudinal designs to elucidate further the interplay between sleep, mood stabilizers, and the course of illness.