zaleplon

General Information

Zaleplon is a short-acting non-benzodiazepine hypnotic (“Z-drug”) approved for insomnia, primarily targeting sleep onset.

Because duration is short, zaleplon is generally a better fit for difficulty falling asleep than for frequent nighttime awakenings; if sleep maintenance is the primary problem, consider other options rather than increasing hypnotic burden.

Key safety issues are complex sleep behaviors (boxed warning), next-day impairment (especially if taken with less than a full night of sleep remaining), and additive sedation with alcohol or other CNS depressants —risks that are amplified in older adults and in serious mental illness with polypharmacy.

The zaleplon compare view, zaleplon evidence feed, and zaleplon print page can support aligning sleep goals with safety planning.

Treat zaleplon as a time-limited adjunct alongside CBT-I and sleep hygiene; avoid chronic, open-ended refills. Use short prescriptions, define a stop plan, and discontinue if complex sleep behaviors or unsafe next-day impairment emerge.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Positive allosteric modulator of GABA-A receptors producing hypnotic effects.

Classified as a “Z-drug”; hypnotic/sedative effects are dose dependent and interact strongly with other CNS depressants.

Like other hypnotics, zaleplon can reduce symptoms but does not treat the underlying cause of insomnia; pair medication use with behavioral sleep strategies and treatment of comorbid psychiatric conditions.

• GABA-A receptor facilitation (non-benzodiazepine hypnotic class).

Metabolism and Pharmacokinetics

• Rapid absorption (Tmax ~1 hour) with terminal half-life ~1 hour (label).
• Extensively metabolized primarily by aldehyde oxidase and to a lesser extent by CYP3A4 (label).
• High-fat meals delay absorption and may reduce effect on sleep onset (label).
• Very short half-life can reduce carryover impairment, but it also limits usefulness for sleep maintenance complaints; match agent selection to the sleep pattern.

Dosing and Administration

• Recommended dose is 10 mg immediately before bedtime or after going to bed and having difficulty falling asleep; elderly/debilitated patients generally use 5 mg (label).
• Do not take unless able to get a full night’s sleep (7–8 hours) before needing to be active again (label).
• Avoid combining with alcohol or other sedatives; reassess frequently and avoid open-ended refills.
• Avoid redosing if sleep does not occur quickly; instead reassess the insomnia diagnosis and drivers (sleep apnea, substances, mood episodes) before escalating or adding sedatives.

Monitoring & Labs

• Assess next-day impairment (driving, work, falls) after initiation and dose changes; lower the dose or stop if safety is compromised.
• Screen for complex sleep behaviors and discontinue immediately if they occur.
• Reassess for untreated sleep apnea, substance use, and mood episodes when insomnia persists rather than escalating hypnotics.
• If continued beyond a brief course, plan taper attempts and reinforce CBT-I to reduce rebound insomnia.

Sources: FDA/DailyMed label; AASM insomnia guideline; evidence reviews.

Adverse Effects

Interactions

• Avoid alcohol and other CNS depressants (opioids, benzodiazepines, sedating antipsychotics).
• Inhibitors/inducers of aldehyde oxidase and CYP3A4 can alter exposure (label).
• Avoid combining with other sedative-hypnotics when possible; if combinations are unavoidable, start lower and increase follow-up frequency to reduce falls and driving risk.

Other Useful Information

• Favor CBT-I and sleep hygiene first; use zaleplon for short, clearly bounded courses with stop plans.
• If insomnia is chronic, treat underlying drivers rather than escalating hypnotic doses.
• Use short prescriptions with planned follow-up; discontinue if complex sleep behaviors, next-day impairment, or unsafe nighttime behaviors occur.

References

1. Zaleplon prescribing information — DailyMed (2025)
2. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline — Journal of Clinical Sleep Medicine (2017)
3. Efficacy and Acceptability of Pharmacological Interventions for Insomnia in Patients With Severe Mental Illness — Acta Psychiatrica Scandinavica (2025)
4. Residual effects of medications for sleep disorders on driving performance — European Neuropsychopharmacology (2024)