What are the recommended medications for managing sleep-wake disorders?

Recommended Medications for Managing Sleep-Wake Disorders

For managing sleep-wake disorders, melatonin receptor agonists are the first-line pharmacological treatment for circadian rhythm sleep-wake disorders, while modafinil is recommended for disorders of excessive sleepiness such as narcolepsy, obstructive sleep apnea, and shift work disorder. 1, 2

Circadian Rhythm Sleep-Wake Disorders

Delayed Sleep-Wake Phase Disorder (DSWPD)

• Melatonin is recommended for treatment of DSWPD, with administration timed appropriately based on the individual's circadian rhythm 1
• Timing of administration is critical - for most individuals with periods longer than 24 hours, melatonin should be given about 6 hours before desired bedtime 3
• Low doses (e.g., 0.5 mg) that are not soporific are preferable to avoid unwanted sedation 3

Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD)

• Melatonin receptor agonists like tasimelteon are particularly effective for N24SWD, especially in blind individuals 1, 3
• Tasimelteon has been administered 1 hour before target bedtime in clinical studies for N24SWD 3
• Melatonin can effectively adjust the sleep-wake cycle to 24 hours in blind individuals with N24SWD 4

Advanced Sleep-Wake Phase Disorder (ASWPD)

• Evening light therapy is suggested for ASWPD patients rather than pharmacological treatment 5
• No evidence supports the use of sleep-promoting medications, melatonin agonists, or wakefulness-promoting medications for ASWPD 5

Irregular Sleep-Wake Rhythm Disorder (ISWRD)

• Melatonin receptor agonists are effective for treating ISWRD 1
• However, studies evaluating melatonin for ISWRD in patients with Alzheimer's disease have shown inconsistent results 1

Disorders of Excessive Sleepiness

Narcolepsy

• Modafinil is FDA-approved to improve wakefulness in adult patients with excessive sleepiness associated with narcolepsy 2
• Starting dose for elderly patients should be 100 mg once upon awakening in the morning, which can be increased at weekly intervals as necessary 5
• Typical doses range from 200 to 400 mg per day 5

Obstructive Sleep Apnea (OSA)

• Modafinil is indicated to treat excessive sleepiness but not as treatment for the underlying obstruction in OSA 2
• Patients should continue their prescribed OSA treatments (e.g., CPAP) while taking modafinil 2

Shift Work Disorder (SWD)

• Modafinil is FDA-approved for improving wakefulness in adults with excessive sleepiness associated with shift work disorder 2

Special Considerations

Elderly Patients

• For insomnia in elderly patients, eszopiclone (1-2 mg) is recommended as a first-line treatment due to its efficacy in improving sleep onset and maintenance with minimal impact on sleep architecture 6
• Zolpidem (5 mg) and zolpidem controlled-release (6.25 mg) are alternatives for specific insomnia presentations 6
• Ramelteon (8 mg) may be considered for patients with primarily sleep onset difficulties 6, 7
• Elderly patients have reduced clearance of sedative-hypnotics and increased sensitivity to peak drug effects, requiring lower starting doses 6

Patients with History of Addiction

• Ramelteon is suggested for sleep onset insomnia in patients with addiction history 7
• Benzodiazepines and non-benzodiazepine hypnotics should be avoided due to significant risk of dependence and abuse 7
• Modafinil is a federally controlled substance (C-IV) because it can be abused or lead to dependence 2

Non-Pharmacological Interventions

• Maintain stable bed times and rising times 7
• Avoid caffeine, nicotine, and alcohol 7
• Limit daytime napping to 30 minutes and avoid napping after 2 pm 7
• Use the bedroom only for sleep and sex 7
• Leave the bedroom if unable to fall asleep and return only when sleepy 7
• Light therapy is particularly effective for circadian rhythm disorders - bright light in the early morning for DSWPD and bright light in the evening for ASWPD 4

Monitoring and Follow-up

• More frequent follow-up is necessary when starting a medication or adjusting doses 5
• Monitor for adverse effects of stimulants, including hypertension, palpitations, arrhythmias, irritability, or behavioral manifestations 5
• Assess functional ability due to residual sleepiness, as medications like modafinil generally improve but do not eliminate sleepiness 5
• The Epworth Sleepiness Scale (ESS) is a useful tool for monitoring subjective sleepiness and response to therapy 5

Cautions and Pitfalls

• Administering melatonin or tasimelteon at bedtime will entrain individuals with non-24 but at an abnormally late time, resulting in continued problems with sleep and alertness 3
• Benzodiazepines should be avoided in elderly patients due to increased risk of falls, cognitive impairment, and dependence 6
• Modafinil may reduce the effectiveness of hormonal birth control methods 2
• Modafinil may cause serious side effects including severe rash or allergic reactions 2
• Sleep-promoting medications should be administered on an empty stomach to maximize effectiveness 6