Can naltrexone contribute to daytime sleepiness?

Naltrexone and Daytime Sleepiness

Yes, naltrexone can contribute to daytime sleepiness as a side effect, particularly when first starting treatment. 1

Mechanism and Evidence

Naltrexone is an opioid antagonist primarily used for alcohol dependence and opioid use disorder. The FDA drug label specifically lists lethargy and somnolence as reported side effects, particularly when naltrexone is used in combination with certain medications like thioridazine 1.

Research on naltrexone's effects on sleep and wakefulness shows mixed results:

• A recent 2024 study found that naltrexone (50mg) was associated with worse subjective sleep quality and increased daytime sleepiness compared to placebo, as measured by the Stanford Sleepiness Scale 2.

• Interestingly, a 1996 study comparing sleep parameters between methadone-treated and naltrexone-treated patients found that the naltrexone group actually showed the shortest sleep latency and longest total sleep time compared to both methadone users and controls 3. This suggests naltrexone might improve some aspects of sleep while potentially contributing to daytime sleepiness.

• A 2010 Cochrane review specifically identified daytime sleepiness as a reported sedative side effect of naltrexone treatment for alcohol dependence (Risk Difference 0.09; 95% CI 0.05 to 0.14) 4.

Clinical Considerations

When prescribing naltrexone, consider these important factors:

1. Timing of administration: Taking naltrexone earlier in the day may help minimize daytime sleepiness.

2. Dose adjustment: Starting with a lower dose and gradually increasing may help reduce sedative side effects.

3. Patient monitoring: Patients should be advised about the potential for daytime sleepiness, especially when:

   • Operating heavy machinery
   • Driving vehicles
   • Performing tasks requiring alertness

4. Sleep disorders: In patients with sleep disorders like obstructive sleep apnea (OSA), the effects of naltrexone may be complex. While some older research suggested naltrexone might improve blood gas patterns in OSA 5, more recent evidence indicates it may worsen nocturnal oxygen saturation and subjective sleep quality 2.

Medication Interactions

Be particularly cautious about increased sedation when naltrexone is combined with:

• Thioridazine (specifically mentioned in FDA labeling) 1
• Other CNS depressants
• Medications known to cause drowsiness

Patient Counseling Points

• Inform patients that daytime sleepiness is a possible side effect of naltrexone
• Advise patients to avoid driving or operating heavy machinery until they know how naltrexone affects them 1
• Encourage patients to report persistent or severe daytime sleepiness, as dose adjustments or timing changes may be needed

Conclusion

While naltrexone has proven efficacy for alcohol dependence and opioid use disorder, daytime sleepiness is a recognized side effect that should be monitored. Patients should be informed of this potential effect before starting treatment, and appropriate precautions should be taken, especially during the initial treatment period.