Non-benzodiazepine hypnotic (“Z-drug”)
Selectively binds to the benzodiazepine-1 (BZ1) receptor subtype of the GABA-A receptor complex, enhancing GABA-mediated inhibition to promote sleep initiation with minimal anxiolytic, anticonvulsant, or muscle-relaxant effects
Short-term treatment of insomnia; immediate-release formulation is indicated for sleep-onset insomnia; controlled-release formulation for both sleep-onset and sleep-maintenance insomnia; sublingual formulation (Intermezzo) for middle-of-the-night awakenings when at least four hours of sleep time remain.
Adjustment-related insomnia, sleep disruption associated with depression or posttraumatic stress disorder (PTSD), and anxiety-related insomnia.
Immediate-release tablet, controlled-release tablet, sublingual tablet, and oral spray.
Typical starting dose for the immediate-release formulation is 5 mg nightly in females and older adults, and 5 to 10 mg nightly in males. For the controlled-release formulation, the initial dose is 6.25 mg nightly, which may be increased to 12.5 mg if needed. The Intermezzo sublingual tablet is typically started at 1.75 mg in females and 3.5 mg in males for middle-of-the-night awakenings.
5 to 10 mg nightly for the immediate-release formulation, 6.25 to 12.5 mg nightly for the controlled-release formulation, and 1.75 to 3.5 mg for the sublingual formulation.
Rapid onset and short half-life of approximately 2.5 hours for the immediate-release form and 2.8 to 2.9 hours for the controlled-release form. It is primarily metabolized by CYP3A4, with slower clearance in elderly patients.
Sedation, dizziness, headache, nausea, and next-day somnolence.
Complex sleep-related behaviors such as sleepwalking or sleep-driving, hallucinations, confusion, and memory impairment.
Monitor sleep latency and duration, next-day alertness, and behavioral changes. Assess for misuse, paradoxical reactions, and any history of complex sleep behaviors.
Risk of complex sleep behaviors, including sleepwalking, sleep-driving, and engaging in other activities while not fully awake, which may result in serious injury or death.
Use with caution in older adults, individuals with dementia, traumatic brain injury (TBI), or elevated fall risk. Elderly patients and women are particularly susceptible to next-day sedation, confusion, and psychomotor impairment due to slower zolpidem clearance. Zolpidem should be initiated at the lowest effective dose and used for the shortest duration necessary. It is not recommended for chronic use in older adults, and should be avoided in those with a history of complex sleep behaviors or significant respiratory impairment.