What is the best first‑line medication for an adult with sleep‑onset insomnia and prolonged sleep latency?

Best Initial Medication for Sleep‑Onset Insomnia and Sleep Latency

For adults with sleep‑onset insomnia and prolonged sleep latency, zaleplon 10 mg (5 mg if age ≥65 years) or zolpidem 10 mg (5 mg if age ≥65 years) are the recommended first‑line pharmacologic agents after initiating Cognitive Behavioral Therapy for Insomnia (CBT‑I), with zaleplon preferred when minimal next‑day sedation is critical and zolpidem preferred when some sleep‑maintenance benefit is also desired. 1

Mandatory First‑Line Behavioral Therapy

• The American Academy of Sleep Medicine and the American College of Physicians issue a strong recommendation that all adults with chronic insomnia receive CBT‑I as the initial treatment before or alongside any medication, because CBT‑I provides superior long‑term efficacy with sustained benefits after discontinuation, whereas medication effects cease when stopped. 1
• Core CBT‑I components include stimulus control (use the bed only for sleep, leave the bed if unable to fall asleep within ~20 minutes), sleep restriction (limit time in bed to approximate actual sleep time plus 30 minutes), relaxation techniques, and cognitive restructuring of maladaptive sleep beliefs. 1
• CBT‑I can be delivered via individual therapy, group sessions, telephone‑based programs, web‑based modules, or self‑help books; all formats demonstrate comparable efficacy. 1

First‑Line Pharmacologic Options for Sleep‑Onset Insomnia

Zaleplon (Preferred for Pure Sleep‑Onset Difficulty)

• Zaleplon 10 mg (5 mg if age ≥65 years or hepatic impairment) has an ultrashort half‑life of ~1 hour, providing rapid sleep initiation with minimal next‑day sedation; it should be taken immediately before bedtime or after the patient has been in bed and is unable to fall asleep, ensuring at least 4 hours remain before the planned awakening. 1, 2
• Zaleplon reduces sleep‑onset latency and is specifically recommended by the American Academy of Sleep Medicine for sleep‑onset insomnia, though it is less effective for sleep maintenance. 1, 2
• Zaleplon 5 and 10 mg do not impair psychomotor function or memory even immediately after the dose in studies of volunteers and patients with insomnia, making it the safest choice when next‑day driving or cognitive performance is critical. 3
• Tolerance to the hypnotic effects of zaleplon generally does not develop during 5 weeks of treatment, and rebound insomnia is not observed after sudden discontinuation of up to 12 months of treatment with zaleplon 5 and 10 mg/night. 3, 4

Zolpidem (Preferred When Some Sleep‑Maintenance Benefit Is Needed)

• Zolpidem 10 mg (5 mg if age ≥65 years) has a longer half‑life of ~2.4 hours and is effective for both sleep‑onset and sleep‑maintenance insomnia; it should be taken within 30 minutes of bedtime with at least 7 hours remaining before the planned awakening. 1, 2, 5
• Zolpidem 10 mg shortens sleep‑onset latency by ~25 minutes and increases total sleep time by ~29 minutes compared with placebo, demonstrating clinically significant improvements in both objective sleep latency and total sleep time. 1, 2
• The FDA has lowered the recommended starting dose of zolpidem to 5 mg for immediate‑release formulations, particularly for women and older adults, due to cognitive and behavioral changes and driving impairment. 1, 2
• Zolpidem was superior to placebo on objective (polysomnographic) measures of sleep latency, sleep duration, and number of awakenings in controlled trials of both transient and chronic insomnia. 5

Ramelteon (Preferred for Patients with Substance‑Use History)

• Ramelteon 8 mg is a melatonin‑receptor agonist with no abuse potential, no DEA scheduling, and no withdrawal symptoms, making it appropriate for patients with a history of substance use; it primarily improves sleep‑onset latency. 1, 6
• Ramelteon does not impair next‑day cognitive or motor performance, unlike benzodiazepines and Z‑drugs (zolpidem, eszopiclone), which commonly cause morning grogginess and cognitive impairment. 1

Dosing Adjustments for Special Populations

• For adults ≥65 years, maximum doses are reduced: zaleplon ≤5 mg, zolpidem ≤5 mg, to mitigate heightened sensitivity and fall risk. 1, 2
• In hepatic impairment, zaleplon and zolpidem doses should be limited (maximum 5 mg for both) because of reduced drug clearance. 1

Safety Monitoring and Duration of Use

• Reassess patients after 1–2 weeks of therapy to evaluate changes in sleep‑onset latency, total sleep time, nocturnal awakenings, and daytime functioning, and to monitor for adverse effects such as morning sedation, cognitive impairment, and complex sleep behaviors. 1
• Screen for complex sleep behaviors (e.g., sleep‑driving, sleep‑walking, sleep‑eating) at every visit; discontinue the hypnotic immediately if such behaviors occur. 1, 5
• FDA labeling limits hypnotic use to ≤4 weeks for acute insomnia; evidence beyond 4 weeks is limited, and continuation requires documented rationale and periodic reassessment. 1, 5
• All benzodiazepine‑receptor agonists carry risks of daytime impairment, driving impairment, falls, fractures, and cognitive decline; therefore, prescribe the lowest effective dose for the shortest necessary duration. 1

Medications Explicitly Not Recommended for Sleep‑Onset Insomnia

• Over‑the‑counter antihistamines (e.g., diphenhydramine, doxylamine) are not recommended due to lack of efficacy, strong anticholinergic effects (confusion, urinary retention, falls, daytime sedation), and rapid tolerance development within 3–4 days. 1, 7
• Traditional benzodiazepines (e.g., lorazepam, temazepam, clonazepam) should be avoided as first‑line treatment due to higher risk of dependency, falls, cognitive impairment, and respiratory depression compared to non‑benzodiazepines. 1, 6
• Antipsychotics (e.g., quetiapine, olanzapine) must not be used for primary insomnia; evidence of benefit is weak and they carry significant risks including weight gain, metabolic syndrome, extrapyramidal symptoms, and increased mortality in the elderly. 1, 6
• Melatonin supplements are not recommended for chronic insomnia in adults, producing only an ~9‑minute reduction in sleep latency with insufficient supporting evidence. 1
• Trazodone is not recommended for sleep‑onset insomnia because it yields only an ~10‑minute reduction in sleep latency with no improvement in subjective sleep quality, and adverse events occur in ~75% of older adults. 1

Common Pitfalls to Avoid

• Do not prescribe hypnotics as first‑line monotherapy without attempting CBT‑I; this violates strong guideline recommendations and results in less durable benefit. 1
• Do not use adult dosing in older adults; age‑adjusted dosing (e.g., zaleplon ≤5 mg, zolpidem ≤5 mg for ≥65 years) is essential to reduce fall risk. 1, 2
• Do not combine multiple sedating agents (e.g., adding a benzodiazepine to zaleplon or zolpidem), which markedly increases the risk of respiratory depression, cognitive impairment, falls, and complex sleep behaviors. 1
• Do not continue hypnotics beyond 4 weeks without periodic reassessment (every 2–4 weeks) to evaluate efficacy, side effects, and ongoing need; taper after 3–6 months if effective. 1, 5
• Do not prescribe zaleplon for sleep‑maintenance problems; its ~1‑hour half‑life makes it ineffective for wake‑after‑sleep‑onset complaints. 1, 2