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<p>Lithium remains a cornerstone in bipolar disorder treatment, yet a narrow therapeutic index and variable patient response hinder its clinical use. The timing of lithium administration, a potentially crucial determinant of efficacy and safety, has been largely overlooked. Here we highlight the bidirectional relationship between lithium and the circadian system: lithium alters molecular clocks, while circadian rhythms influence the pharmacokinetics, pharmacodynamics and side effects profile of lithium. An evaluation of clinical studies of lithium treatment in bipolar disorder over the last 50 years reveals that nearly 90% of reports do not mention lithium administration timing, and none directly assess its impact. We propose that aligning lithium dosing with individual circadian patterns and biological rhythms could improve therapeutic outcomes and reduce toxicity. Drawing from chronobiology, pharmacology and transcriptomic evidence, we advocate for integrating chronotherapeutic strategies into future lithium trials. This approach offers a timely direction to enhance precision psychiatry and mood disorder management.</p>

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Chronotherapy considerations in lithium treatment for bipolar disorder

  • 期刊论文

  • 发表日期：

    2026年6月17日

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  • Apoorva Bhatnagar,
  • Saibal Saha,
  • Greg Murray,
  • Sandipan Ray

摘要

Lithium remains a cornerstone in bipolar disorder treatment, yet a narrow therapeutic index and variable patient response hinder its clinical use. The timing of lithium administration, a potentially crucial determinant of efficacy and safety, has been largely overlooked. Here we highlight the bidirectional relationship between lithium and the circadian system: lithium alters molecular clocks, while circadian rhythms influence the pharmacokinetics, pharmacodynamics and side effects profile of lithium. An evaluation of clinical studies of lithium treatment in bipolar disorder over the last 50 years reveals that nearly 90% of reports do not mention lithium administration timing, and none directly assess its impact. We propose that aligning lithium dosing with individual circadian patterns and biological rhythms could improve therapeutic outcomes and reduce toxicity. Drawing from chronobiology, pharmacology and transcriptomic evidence, we advocate for integrating chronotherapeutic strategies into future lithium trials. This approach offers a timely direction to enhance precision psychiatry and mood disorder management.