Best Sleeping Medication During Withdrawal
For patients experiencing withdrawal (alcohol, benzodiazepine, or opioid), avoid benzodiazepines and Z-drugs entirely—instead, use trazodone 25-200 mg at bedtime as first-line pharmacotherapy, combined with cognitive behavioral therapy for insomnia (CBT-I). 1, 2, 3
Critical Context: Type of Withdrawal Matters
The optimal sleep medication depends critically on which substance the patient is withdrawing from:
Alcohol Withdrawal
- Gabapentin is superior to lorazepam for sleep disturbances during alcohol withdrawal, particularly in patients with multiple previous withdrawal episodes 4
- Gabapentin-treated patients reported significantly reduced sleep disturbances and daytime sleepiness compared to lorazepam 4
- Lorazepam caused rebound insomnia during alcohol withdrawal, whereas gabapentin did not 4
- Start gabapentin 100-300 mg at bedtime, titrating by 100-300 mg every 1-7 days as tolerated 5
Benzodiazepine or Barbiturate Withdrawal
- Never use additional benzodiazepines or Z-drugs (zolpidem, zaleplon, eszopiclone) for sleep during benzodiazepine withdrawal—this perpetuates dependence 1, 2, 5
- Trazodone 25-200 mg at bedtime is the preferred agent for insomnia during benzodiazepine tapering 5, 3
- Trazodone should be taken shortly after a meal or light snack to optimize absorption 3
- Melatonin 5 mg at bedtime improved sleep quality in patients continuing benzodiazepine use during withdrawal attempts, though it did not enhance discontinuation rates 6
- Gabapentin can help mitigate withdrawal symptoms including insomnia, starting at 100-300 mg at bedtime 5
Opioid Withdrawal
- Clonidine, gabapentin, and dexmedetomidine are recommended adjunctive medications to decrease withdrawal symptoms including insomnia during opioid weaning 1
- These agents are used off-label with limited evidence, but represent safer alternatives than sedative-hypnotics 1
- Methadone provided inadequate control of insomnia during opiate withdrawal, with patients experiencing 4-6 hours of sleep per night even 1 month after admission 7
Cannabis Withdrawal
- Gabapentin, mirtazapine, quetiapine, and zolpidem showed preliminary benefits for sleep difficulties associated with cannabis withdrawal, though evidence quality is low 8
- Mirtazapine requires nightly scheduled dosing (not PRN) due to its 20-40 hour half-life 2
Why NOT Benzodiazepines or Z-Drugs
Benzodiazepines and Z-drugs are contraindicated during withdrawal from any substance for multiple critical reasons:
- Cross-tolerance and dependence risk: Using benzodiazepines during alcohol or sedative withdrawal substitutes one dependence for another 1, 5
- Rebound insomnia: Lorazepam caused significant rebound sleep symptoms during alcohol withdrawal 4
- Respiratory depression risk: Combining benzodiazepines with opioids during opioid withdrawal dramatically increases respiratory depression and death risk 5, 9
- Cognitive impairment and falls: Particularly dangerous in withdrawal states where patients already have altered mental status 1, 2
- Withdrawal syndrome: Benzodiazepine withdrawal itself can cause severe insomnia, seizures, and death—never appropriate to add during another withdrawal syndrome 1, 5
Essential Non-Pharmacologic Foundation
CBT-I must be implemented alongside any pharmacotherapy during withdrawal 1, 2:
- Stimulus control therapy: Go to bed only when sleepy, use bed only for sleep, leave bedroom if unable to sleep within 20 minutes 2
- Sleep restriction therapy: Limit time in bed to actual sleep time, gradually increasing as sleep efficiency improves 2
- Sleep hygiene: Wake at same time daily, avoid caffeine/nicotine before bed, keep bedroom quiet and temperature-regulated 2
- Relaxation techniques: Progressive muscle relaxation, guided imagery, breathing exercises 2
Treatment Algorithm
Step 1: Identify Withdrawal Substance
- Alcohol → Gabapentin preferred (100-300 mg at bedtime, titrate up) 4, 5
- Benzodiazepine/Barbiturate → Trazodone 25-200 mg at bedtime 5, 3
- Opioid → Clonidine or gabapentin as adjunct 1
- Cannabis → Gabapentin or mirtazapine (limited evidence) 8
Step 2: Implement CBT-I Immediately
- Begin stimulus control, sleep restriction, and sleep hygiene education 2
- CBT-I provides superior long-term outcomes compared to medications alone 1, 2
Step 3: Monitor and Adjust
- Assess sleep quality, withdrawal symptoms, and medication side effects at least weekly 5
- For trazodone: Monitor for dizziness, drowsiness, and orthostatic hypotension 3
- For gabapentin: Monitor for dose-dependent dizziness and sedation; adjust in renal insufficiency 5
Step 4: Taper Sleep Medication When Stable
- Once withdrawal is complete and sleep stabilizes (typically 4-8 weeks), gradually taper sleep medication 2
- Continue CBT-I indefinitely for sustained benefit 1, 2
Critical Pitfalls to Avoid
- Never prescribe benzodiazepines or Z-drugs during any withdrawal syndrome—this creates cross-dependence and worsens outcomes 1, 5, 4
- Never use antihistamines (diphenhydramine)—lack efficacy data and cause daytime sedation, delirium risk in elderly 1, 2
- Never use antipsychotics as first-line—problematic metabolic side effects without clear benefit 1
- Never use mirtazapine PRN—requires nightly scheduled dosing due to 20-40 hour half-life 2
- Never combine multiple sedating medications—dramatically increases cognitive impairment, falls, and respiratory depression risk 1, 10
Special Population Considerations
Elderly Patients
- Use lower trazodone doses (25-50 mg initially) due to increased fall risk and orthostatic hypotension 3
- Gabapentin requires more gradual titration and dose adjustment in renal insufficiency 5
Patients with Hepatic Impairment
- Trazodone and gabapentin are safer than benzodiazepines, which have significantly impaired clearance in liver disease 9
- Monitor closely for excessive sedation 9