What is the therapeutic use and safety of Zuranalone (Suvorexant) in treating insomnia and other sleep disorders?

Therapeutic Use and Safety of Suvorexant (Not Zuranalone) for Insomnia

Suvorexant is effective for treating insomnia disorder, improving both global sleep outcomes and specific sleep variables, though its effects are modest and it carries risks of cognitive and behavioral changes. 1

Efficacy for Insomnia

Primary Indications

• Suvorexant is FDA-approved for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance 1
• Suvorexant improves short-term global outcomes and sleep variables for adults with insomnia disorder, though the absolute mean effect versus placebo is small 1
• Clinical trials show that suvorexant reduces wake after sleep onset by 16-28 minutes compared to placebo and improves total sleep time by approximately 10 minutes 2

Mechanism of Action

• Suvorexant is a dual orexin receptor antagonist (DORA), the first in its class, targeting cerebral orexin receptors which contribute to arousal and wakefulness 3
• Unlike traditional hypnotics, suvorexant does not alter the sleep profile but rather prolongs the time spent in each sleep state, potentially promoting more natural sleep 4

Dosing Considerations

• The American Academy of Sleep Medicine suggests using suvorexant as a treatment for sleep maintenance insomnia in adults, based on trials of 10,15/20, and 20 mg doses 2
• Lower doses (5-10 mg) are recommended as a second-line treatment option when cognitive behavioral therapy is unsuccessful 2
• No dose adjustment is needed for advanced age according to the American Geriatrics Society 2

Safety Profile and Adverse Effects

Common Adverse Effects

• Somnolence is the most common adverse effect, occurring in approximately 7% of patients (versus 3% for placebo) 2, 3
• Other common adverse effects include fatigue and abnormal dreams 5

Serious Concerns

• FDA labeling warns of potential cognitive and behavioral changes, including amnesia, anxiety, hallucinations, and other neuropsychiatric symptoms 2
• Observational studies suggest that hypnotic drugs may be associated with infrequent but serious adverse effects, such as dementia, serious injury, and fractures 1
• FDA warnings include risks for daytime impairment, "sleep driving," behavioral abnormalities, and worsening depression 1

Special Populations

• Evidence for most interventions in older adults is insufficient or low strength 1
• The FDA recommends lower dosages than those used in many clinical studies, especially for older adults 1

Clinical Recommendations

Treatment Algorithm

• Cognitive behavioral therapy for insomnia (CBT-I) should be the first-line treatment before considering pharmacologic options 1, 2
• Pharmacologic therapy should only be considered when CBT-I alone is unsuccessful 2
• The FDA has approved pharmacologic therapy for short-term use (4 to 5 weeks), and patients should not continue using these drugs for extended periods 1
• Patients with insomnia that does not remit within 7 to 10 days of treatment should be further evaluated 1

Comparative Effectiveness

• Evidence is insufficient to determine the comparative effectiveness and safety of various pharmacologic treatments for insomnia 1
• Head-to-head studies comparing suvorexant with established hypnotics such as zolpidem and eszopiclone are lacking 3
• Suvorexant carries potential advantages over existing therapies including a better safety profile at approved doses and preservation of natural sleep architecture 4

Important Clinical Considerations

Duration of Treatment

• Evidence is insufficient to evaluate the balance of benefits and harms of long-term use of pharmacologic treatments in adults with chronic insomnia disorder 1
• Most clinical trials evaluating suvorexant were short-term, limiting knowledge about long-term efficacy and safety 1

Special Use Cases

• Suvorexant has shown efficacy in treating vasomotor symptom-associated insomnia disorder in midlife women, reducing both insomnia severity and nighttime hot flash frequency 6
• It may be considered for patients with comorbid conditions, though data for secondary insomnia is more limited than for primary insomnia 4

Monitoring Recommendations

• Monitor for potential side effects, including somnolence, headache, and nightmares when using dual orexin receptor antagonists 2
• Patients should be evaluated for continued need of medication after short-term use 1

Note on Zuranalone

• The evidence provided primarily discusses suvorexant, not zuranalone
• Zuranalone appears to be investigated for postpartum depression with concurrent anxiety and insomnia symptoms, rather than as a primary insomnia treatment 7