Does Latuda (Lurasidone) Affect Sleep?
Yes, lurasidone has beneficial effects on sleep maintenance, specifically increasing total sleep time and reducing nighttime awakenings, though it may also cause somnolence as a side effect.
Sleep-Promoting Effects
Lurasidone improves sleep maintenance without affecting sleep onset. In a controlled polysomnographic study using a 4-hour phase-advance model of transient insomnia, lurasidone 40 mg significantly increased total sleep time by an average of 28.4 minutes compared to placebo, decreased wake time after sleep onset, and increased sleep efficiency 1. Importantly, lurasidone had no effects on sleep onset latency, REM sleep, or slow-wave sleep architecture 1.
The mechanism behind these sleep benefits likely relates to lurasidone's potent 5-HT7 receptor antagonism, combined with its D2, 5-HT2A antagonism and 5-HT1A partial agonism 1. This unique receptor profile distinguishes it from other antipsychotics in terms of sleep modulation 1.
Somnolence as an Adverse Effect
Somnolence is one of the most common side effects of lurasidone, occurring more frequently than with placebo. The FDA labeling data shows varying rates depending on the population and dose 2:
In Adults with Bipolar Depression:
- Monotherapy: Somnolence occurred in 7.3% of patients on lurasidone 20-60 mg and 13.8% on 80-120 mg, compared to 6.5% with placebo 2
- Adjunctive therapy (with lithium or valproate): 11.4% experienced somnolence with lurasidone 20-120 mg versus 5.1% with placebo 2
In Pediatric Patients (10-17 years):
- Somnolence was reported in 11.4% of patients on lurasidone 20-80 mg/day compared to 5.8% with placebo 2
Clinical Implications and Safety Considerations
Lurasidone's potential to impair judgment, thinking, and motor skills requires specific patient counseling. The FDA explicitly warns that patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are certain that lurasidone does not adversely affect them 2.
The somnolence effect may contribute to fall risk, particularly in vulnerable populations. Lurasidone can cause somnolence, postural hypotension, and motor/sensory instability, which may lead to falls and consequently fractures or other injuries 2. Complete fall risk assessments should be performed when initiating treatment and recurrently for patients on long-term therapy 2.
Sleep Disturbance as a Treatment Target
In pediatric bipolar depression, baseline sleep disturbances predict treatment response. Sleep disturbances (assessed as "difficulty with sleep") were identified as "bridge" symptoms with causal associations between depressive and manic symptom clusters 3. The absence of sleep disturbance at baseline was associated with higher rates of sustained recovery (68% vs. 50%, Number Needed to Treat=6) over 6 months compared to patients with sleep disturbances 3.
Dosing Considerations for Sleep Effects
Lurasidone should be administered once-daily at night with food to maximize absorption (which is halved on an empty stomach) and to align with its sleep-promoting effects 4. The recommended starting dose is 40 mg/day, with a dose range of 40-160 mg/day 5. Initial dose titration is not required 5.
Higher doses (160 mg/day) appear better tolerated than lower doses for sedation and somnolence. In pooled analysis, lurasidone 160 mg/day showed no statistically significant Number Needed to Harm values for sedation or somnolence compared to placebo, unlike the 40-120 mg/day doses 6.
Common Pitfalls to Avoid
- Do not prescribe lurasidone without food: Absorption is reduced by 50% when taken on an empty stomach, potentially reducing both therapeutic and sleep-promoting effects 4
- Monitor for excessive daytime sedation: While sleep maintenance improvement is beneficial, excessive somnolence may impair daytime functioning and increase fall risk 2
- Consider timing of administration: Given the somnolence profile, bedtime dosing is most appropriate 4
- Assess fall risk in elderly or vulnerable patients: The combination of somnolence, postural hypotension, and motor impairment requires proactive fall prevention strategies 2