How does lithium affect sleep?

How Lithium Affects Sleep

Lithium improves sleep architecture in bipolar disorder by increasing slow-wave sleep (stages 3-4), reducing REM sleep, and prolonging REM latency, with particularly beneficial effects on sleep quality and duration in women with bipolar I disorder. 1, 2

Sleep Architecture Changes

Lithium produces consistent, measurable alterations in sleep structure that appear therapeutic:

• Increases slow-wave sleep (stages 3 and 4) in depressed patients, which may contribute to its mood-stabilizing effects 1
• Reduces REM sleep percentage and increases REM latency in both normal subjects and depressed patients, with effects correlating directly to plasma lithium levels 1
• Decreases REM intensity (measured as REM activity per minute of sleep) in depressed subjects on both short-term and long-term therapy 1
• Does not significantly alter total sleep time in normal subjects receiving lithium for two weeks 1

Clinical Sleep Benefits in Bipolar Disorder

The therapeutic effects on sleep are most pronounced in specific patient populations:

• Euthymic bipolar I patients taking lithium demonstrate significantly better sleep efficiency (40% improvement) and longer sleep duration (42% improvement) compared to those not on lithium 2
• Women with bipolar I disorder show particularly robust benefits: 23% improvement in overall sleep quality (PSQI scores), 70% better sleep duration scores, and 37% less frequent use of night sedation 2
• Men with bipolar I disorder show minimal sleep quality improvements from lithium, suggesting important sex-based differences in lithium's sleep effects 2
• No significant sleep benefits were observed in bipolar II disorder patients, indicating diagnosis-specific effects 2

Circadian Rhythm Effects

Lithium appears to modulate the circadian system, though evidence remains limited:

• May cause small but significant delays in sleep-wake circadian rhythm with short-term therapy 1
• Associated with shifts toward morningness (earlier chronotype) in meta-analysis, though confidence intervals were wide (SMD: 0.42,95% CI: -0.05 to 0.90) 3
• Increases circadian amplitude (the difference between peak activity and rest) compared to anticonvulsants in one 21-day cohort study 3

Adverse Sleep-Related Effects

While generally beneficial, lithium can cause problematic sleep symptoms, particularly in toxicity:

• Restless legs syndrome (RLS) can be exacerbated or triggered by lithium, along with other psychiatric medications including tricyclic antidepressants and SSRIs 4
• Early lithium toxicity may present with drowsiness and somnolence, which can progress to confusion, stupor, and coma at higher levels 5
• Transient mild discomfort during initial therapy may temporarily disrupt sleep but typically subsides with continued treatment 5

Therapeutic Applications

Lithium's sleep effects have specific clinical utility:

• Sustains antidepressant effects of sleep deprivation therapy: When combined with early morning sleep deprivation (awake 0200-2200 hours), lithium maintains the rapid antidepressant response for at least 30 days, preventing the typical 48-hour relapse 6
• Prevents memory impairment from REM sleep deprivation at doses of 150 mg/kg in animal models, likely by reducing excessive REM rebound that disrupts sleep cycle organization 7
• May be useful for prophylaxis of Kleine-Levin syndrome (recurrent hypersomnia), though evidence remains limited 1

Monitoring Considerations

Given lithium's narrow therapeutic window, sleep-related monitoring is essential:

• Regular serum lithium monitoring is mandatory (twice weekly until stabilized) to prevent toxicity that could worsen sleep disturbances 8, 9
• Therapeutic range of 0.6-1.0 mM should be maintained; levels above 1.5 mEq/L carry increased toxicity risk including severe drowsiness 10, 5
• Sleep quality changes may serve as early indicators of either therapeutic response or emerging toxicity 5