In a generally healthy 55‑year‑old with insomnia refractory to trazodone, which is the preferred first‑line hypnotic: zolpidem, suvorexant (Belsomra), or zaleplon?

Zolpidem is the preferred first-line hypnotic for a 55-year-old with trazodone-refractory insomnia

For a generally healthy 55-year-old who has failed trazodone, zolpidem 10 mg at bedtime is the recommended first-line hypnotic, followed by suvorexant (Belsomra) as a second-line alternative if zolpidem is ineffective or contraindicated; zaleplon should be reserved for isolated sleep-onset difficulty only.

Rationale for Zolpidem as First-Line

• The American Academy of Sleep Medicine (AASM) explicitly recommends zolpidem for both sleep-onset and sleep-maintenance insomnia, with moderate-quality evidence showing a 25-minute reduction in sleep-onset latency, a 29-minute increase in total sleep time, and moderate improvement in subjective sleep quality compared with placebo. 1

• Zolpidem addresses the full spectrum of insomnia symptoms (both initiation and maintenance), whereas zaleplon is effective only for sleep onset and provides minimal benefit for sleep maintenance or total sleep time. 1, 2, 3

• At age 55, the standard adult dose of zolpidem 10 mg is appropriate; dose reduction to 5 mg is reserved for adults ≥65 years or those with hepatic impairment. 1, 4

• Zolpidem has a favorable next-day safety profile when taken at bedtime with at least 7 hours remaining before planned awakening, producing minimal residual psychomotor or cognitive impairment compared with longer-acting benzodiazepines. 5

Why Suvorexant (Belsomra) is Second-Line

• Suvorexant is recommended by the AASM specifically for sleep-maintenance insomnia, reducing wake after sleep onset by 16–28 minutes, but it provides only a 10-minute improvement in total sleep time—substantially less than zolpidem's 29-minute gain. 1, 4

• Suvorexant works through a completely different mechanism (orexin-receptor antagonism) and is best reserved for patients who fail or cannot tolerate benzodiazepine-receptor agonists like zolpidem. 4, 6

• The evidence base for suvorexant is narrower than for zolpidem, with fewer long-term safety data and a higher cost, making it a rational second-line choice rather than initial therapy. 1, 4

Why Zaleplon is Not Preferred in This Case

• Zaleplon is indicated only for sleep-onset insomnia due to its ultra-short half-life (~1 hour); it does not improve sleep maintenance, total sleep time, or sleep quality in most studies. 1, 2, 3

• The AASM guideline data show that zaleplon provides no significant benefit for wake after sleep onset or number of awakenings, limiting its utility to patients with isolated difficulty falling asleep at bedtime or middle-of-the-night awakenings when ≥4 hours remain before planned awakening. 1, 2

• For a patient who has already failed trazodone (which itself provides minimal benefit), choosing an agent with broader efficacy across all insomnia domains is clinically prudent. 1, 4

Essential Concurrent Behavioral Therapy

• Cognitive-Behavioral Therapy for Insomnia (CBT-I) must be initiated or optimized alongside any hypnotic, as it provides superior long-term efficacy and sustained benefits after medication discontinuation; pharmacotherapy should supplement—not replace—behavioral interventions. 1, 4

• 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 negative beliefs about sleep. 4

• CBT-I can be delivered via individual therapy, group sessions, telephone, web-based modules, or self-help books, all of which demonstrate comparable effectiveness and make the intervention feasible even in resource-limited settings. 4

Dosing and Administration

• Zolpidem 10 mg should be taken within 30 minutes of bedtime with at least 7 hours remaining before the planned time of awakening to minimize next-day impairment. 4, 5

• Reassess efficacy and adverse effects after 1–2 weeks, evaluating changes in sleep-onset latency, total sleep time, nocturnal awakenings, daytime functioning, and side effects such as morning sedation, dizziness, or headache. 4

• FDA labeling recommends hypnotics for short-term use (≤4 weeks) for acute insomnia; evidence beyond 4 weeks is limited, so plan for periodic reassessment and eventual tapering using CBT-I to support discontinuation. 4, 5

Critical Safety Warnings

• All benzodiazepine-receptor agonists (including zolpidem) carry FDA warnings about complex sleep behaviors such as sleep-driving, sleep-walking, and sleep-eating; discontinue zolpidem immediately if such behaviors occur. 4

• Alcohol must be avoided while taking zolpidem because it markedly increases the risk of complex sleep behaviors, respiratory depression, and next-day impairment. 4

• Next-day driving impairment can occur even when the patient feels fully awake, particularly if fewer than 7 hours have elapsed since dosing; counsel patients to avoid driving or operating machinery until they know how zolpidem affects them. 4, 5

• Falls, fractures, and cognitive impairment are increased with all hypnotics, especially in older adults; although this patient is 55 years old and not yet in the high-risk elderly category, these risks should still be discussed. 4

If Zolpidem Fails or is Contraindicated

• Switch to suvorexant 10 mg at bedtime if zolpidem is ineffective after 1–2 weeks or if the patient experiences intolerable side effects; suvorexant's orexin-antagonist mechanism provides an alternative pathway for sleep improvement. 4, 6

• Low-dose doxepin 3–6 mg is another second-line option specifically for sleep-maintenance insomnia, reducing wake after sleep onset by 22–23 minutes with minimal anticholinergic effects and no abuse potential. 1, 4

• Eszopiclone 2–3 mg addresses both sleep onset and maintenance, increasing total sleep time by 28–57 minutes and providing moderate-to-large improvements in sleep quality, but it carries a higher risk of complex sleep behaviors and next-day impairment compared with zolpidem. 1, 4

Common Pitfalls to Avoid

• Starting zaleplon in a patient with mixed sleep-onset and sleep-maintenance symptoms will leave the maintenance component untreated and is likely to result in continued dissatisfaction. 1, 2, 3

• Initiating pharmacotherapy without concurrent CBT-I leads to less durable benefit and higher rates of relapse after medication discontinuation. 1, 4

• Combining multiple sedative agents (e.g., adding a benzodiazepine or another Z-drug to zolpidem) markedly increases the risk of respiratory depression, cognitive impairment, falls, and complex sleep behaviors; avoid polypharmacy. 4

• Continuing hypnotic therapy long-term without periodic reassessment (every 2–4 weeks initially, then every 4–6 weeks) to evaluate efficacy, side effects, and the need for ongoing medication. 4

• Using trazodone again or escalating its dose after it has already failed; the AASM explicitly recommends against trazodone for insomnia due to minimal benefit (only ~10 minutes reduction in sleep latency and ~8 minutes reduction in wake after sleep onset) with no improvement in subjective sleep quality and harms that outweigh benefits. 1, 4