Zolpidem Prescribing for Adult Inpatients with Acute Insomnia and Low Fall Risk
For an adult inpatient with acute insomnia and low fall risk, prescribe zolpidem 10 mg (5 mg for women) taken immediately before bedtime on an empty stomach for ≤4 weeks, combined with Cognitive Behavioral Therapy for Insomnia (CBT-I), while monitoring for complex sleep behaviors and next-day impairment. 1
Dose and Formulation
- Men: Start zolpidem immediate-release 10 mg at bedtime 1
- Women: Start zolpidem immediate-release 5 mg at bedtime due to 45% slower clearance and higher blood levels, which increase next-day impairment risk 1, 2
- Elderly patients (≥65 years): Use 5 mg regardless of sex due to increased sensitivity, fall risk, and slower metabolism 1, 2
- Hepatic impairment: Use 5 mg once daily; avoid in severe hepatic impairment as it may contribute to encephalopathy 2
The FDA mandated these lower doses for women in 2013 specifically because of driving impairment and psychomotor dysfunction the next morning, particularly at the 10 mg dose 1. Despite this warning, approximately 50% of female veterans continued receiving high doses after 2013, highlighting a critical translation gap between guidelines and practice 1.
Administration Guidelines
- Take immediately before bedtime with at least 7–8 hours remaining before planned awakening 1
- Take on an empty stomach to maximize effectiveness; food delays absorption and reduces efficacy 1
- Do not take with or immediately after a meal, as this may delay the drug's effect 1
- Avoid alcohol or other CNS depressants due to additive effects on psychomotor performance and respiratory depression 1, 3
Duration of Treatment
- FDA labeling indicates short-term use (≤4 weeks) for acute insomnia 1, 2
- Reassess after 1–2 weeks to evaluate sleep-onset latency, total sleep time, nocturnal awakenings, daytime functioning, and adverse effects 1
- If insomnia persists beyond 7–10 days, evaluate for underlying sleep disorders (sleep apnea, restless legs syndrome, circadian rhythm disorders) or psychiatric conditions 1, 3, 2
Expected Clinical Effects
- Reduces sleep-onset latency by approximately 10–19 minutes compared to placebo 1, 2
- Increases total sleep time by approximately 23–30 minutes with standard formulation 1, 2
- Effects are evident from the first night of treatment 1
- Zolpidem has a short half-life (1.5–3.2 hours) and is most effective for sleep-onset insomnia, with limited efficacy for sleep maintenance 3, 4
Mandatory Concurrent Behavioral Therapy
The American Academy of Sleep Medicine and American College of Physicians issue a strong recommendation that all adults with insomnia receive Cognitive Behavioral Therapy for Insomnia (CBT-I) as first-line treatment, either before or alongside any medication. 5, 3
CBT-I provides superior long-term efficacy compared to medications, with sustained benefits after discontinuation 5
Core components include:
- Stimulus control therapy (use bed only for sleep; leave bed if unable to sleep within ~20 minutes) 5
- Sleep restriction therapy (limit time in bed to actual sleep time + 30 minutes) 5
- Relaxation techniques (progressive muscle relaxation, breathing exercises) 5
- Cognitive restructuring (challenge maladaptive beliefs about sleep) 5
- Sleep hygiene education (consistent wake time, avoid caffeine ≥6 hours before bed, eliminate screens ≥1 hour before sleep) 5
Initiating zolpidem without concurrent CBT-I is the single biggest mistake in insomnia management and results in less durable benefit 5
Critical Safety Monitoring
Complex Sleep Behaviors (FDA Black Box Warning)
- Screen for complex sleep behaviors at every clinical visit (sleep-driving, sleep-walking, sleep-eating) and discontinue zolpidem immediately if any occur 1
- These behaviors can be life-threatening and are not dose-dependent 1
Psychiatric Safety
- Assess for worsening depression, suicidal ideation, anxiety, hallucinations, and memory impairment at each follow-up 1
- Zolpidem use is associated with increased risk of suicide attempts and completions (OR 2.08; 95% CI 1.83–2.63) independent of pre-existing psychiatric illness 1, 6
Fall and Fracture Risk
- Zolpidem increases fall risk (OR 4.28; P<0.001) and hip fracture risk (RR 1.92; 95% CI 1.65–2.24) even in non-elderly patients 6
- In inpatients, 80.8% of adverse drug reactions are CNS-related (confusion, dizziness, daytime sleepiness) 6
Next-Day Impairment
- Women and elderly patients are at highest risk for next-day driving impairment lasting up to 8 hours after dosing 1, 2
- Patients often do not perceive their impairment, so counsel them to avoid driving or operating machinery until fully awake 1
Memory Impairment
- Zolpidem can cause anterograde amnesia, particularly at doses ≥10 mg or when taken with alcohol 2
- Memory impairment is most pronounced during the first 90 minutes after dosing 2
Alternative Options
If Zolpidem is Ineffective After 1–2 Weeks:
For sleep-onset insomnia:
- Zaleplon 10 mg (5 mg if elderly) – ultrashort half-life (~1 hour), minimal next-day sedation 5
- Ramelteon 8 mg – melatonin-receptor agonist with no abuse potential, not DEA-scheduled 5
For sleep-maintenance insomnia:
- Low-dose doxepin 3–6 mg – reduces wake after sleep onset by 22–23 minutes, minimal anticholinergic effects, no abuse potential 5
- Suvorexant 10 mg – orexin-receptor antagonist, reduces wake after sleep onset by 16–28 minutes 5
For combined sleep-onset and maintenance:
- Eszopiclone 2–3 mg (1 mg if elderly) – increases total sleep time by 28–57 minutes 5
- Zolpidem extended-release 12.5 mg (6.25 mg if elderly) – maintains therapeutic levels for >6 hours, though evidence quality is low 1, 3
Agents Explicitly NOT Recommended:
- Trazodone – only 10-minute reduction in sleep latency, no improvement in subjective sleep quality, harms outweigh benefits 5
- Over-the-counter antihistamines (diphenhydramine, doxylamine) – lack efficacy, strong anticholinergic effects, tolerance develops in 3–4 days 5
- Antipsychotics (quetiapine, olanzapine) – weak evidence, significant risks (weight gain, metabolic syndrome, extrapyramidal symptoms) 5
- Benzodiazepines (lorazepam, temazepam) – higher risk of dependence, falls, cognitive impairment, dementia, and fractures 5
Common Pitfalls to Avoid
- Prescribing 10 mg to women despite FDA warnings – this occurred in roughly half of female patients even after the 2013 mandate 1
- Failing to implement CBT-I before or alongside pharmacotherapy 5
- Continuing zolpidem beyond 4 weeks without documented rationale and periodic reassessment 1, 2
- Combining multiple sedating agents (e.g., adding a benzodiazepine to zolpidem), which markedly increases respiratory depression, falls, and cognitive impairment 5, 3
- Using adult dosing in elderly patients – age-adjusted dosing (5 mg maximum) is mandatory to reduce fall risk 1, 2
- Prescribing without matching the drug's pharmacologic profile to the insomnia phenotype – zolpidem's short half-life makes it ineffective for middle-of-night awakenings or early-morning awakening 3
Withdrawal and Discontinuation
- Rapid dose decrease or abrupt discontinuation may produce withdrawal symptoms including rebound insomnia, anxiety, and rarely seizures (most cases at doses ≥450 mg/day, but reported as low as 160 mg/day) 1, 6
- Taper gradually by reducing the dose by approximately 25% every 1–2 weeks while maintaining CBT-I techniques 1
- Rebound insomnia: Sleep-onset latency increases by 13 minutes on the first night after stopping zolpidem (95% CI 4.3–21.7; P<0.01) 6
Special Populations
Pregnancy and Lactation
- FDA Category C – avoid during pregnancy; increased incidence of low birth weight (OR 1.39), preterm delivery (OR 1.49), small-for-gestational-age babies (OR 1.34), and cesarean deliveries (OR 1.74) 6
- Breastfeeding: Monitor infants for excess sedation, hypotonia, and respiratory depression; consider interrupting breastfeeding and pumping/discarding milk for 23 hours (approximately 5 elimination half-lives) after administration 2
Respiratory Conditions
- Use caution in patients with asthma, COPD, or sleep apnea due to potential respiratory depression 1