Benzodiazepines for Insomnia
Direct Recommendation
Benzodiazepines should NOT be used as first-line treatment for insomnia and are only recommended when first-line benzodiazepine receptor agonists (Z-drugs) or ramelteon have failed, with use limited to the lowest effective dose for the shortest duration possible (typically less than 4 weeks). 1
Treatment Algorithm for Insomnia
Step 1: First-Line Treatment
- Cognitive Behavioral Therapy for Insomnia (CBT-I) is the mandatory initial treatment for all adults with chronic insomnia before any pharmacotherapy is considered. 1
- CBT-I demonstrates superior long-term efficacy compared to all medications and has minimal adverse effects 1
- CBT-I can be delivered through individual therapy, group sessions, telephone-based programs, web-based modules, or self-help books 2
Step 2: First-Line Pharmacotherapy (if CBT-I insufficient)
When medication is necessary, short/intermediate-acting benzodiazepine receptor agonists (Z-drugs) or ramelteon are recommended as first-line pharmacotherapy, NOT traditional benzodiazepines: 1
- Zolpidem 10 mg (5 mg in elderly) for sleep onset and maintenance 2
- Eszopiclone 2-3 mg for sleep onset and maintenance 2
- Zaleplon 10 mg for sleep onset only 2
- Ramelteon 8 mg for sleep onset 2
Step 3: Second-Line Options
If first-line medications fail or are contraindicated:
- Low-dose doxepin 3-6 mg for sleep maintenance (particularly appropriate for elderly patients) 2, 3
- Suvorexant for sleep maintenance 2
Step 4: Traditional Benzodiazepines (Third-Line)
Only after failure of above options should traditional benzodiazepines be considered: 1
- Temazepam 15 mg for sleep onset and maintenance 2
- Triazolam 0.25 mg for sleep onset (associated with rebound anxiety, not truly first-line) 2
Why Benzodiazepines Are NOT First-Line
Evidence Quality Issues
The American College of Physicians found insufficient evidence to determine the efficacy of benzodiazepines in managing chronic insomnia and insufficient evidence to determine the balance of benefits versus harms 1
Serious Safety Concerns
Dependence and Withdrawal:
- Approximately half of patients prescribed benzodiazepines are treated continuously for at least 12 months despite recommendations against extended use 4, 5
- Abrupt discontinuation can precipitate life-threatening withdrawal reactions including seizures 6
- Protracted withdrawal syndrome can last weeks to more than 12 months 6
Cognitive and Psychomotor Impairment:
- Increased risk of falls, fractures, and motor vehicle accidents, particularly in elderly patients 4
- Memory impairment and decreased alertness 4
- Complex sleep behaviors including sleep-driving, sleep-eating, and sleep-walking with amnesia for events 6
Respiratory Depression:
- Particularly dangerous for patients with sleep apnea or other respiratory conditions 4
Other Serious Risks:
- Increased risk of dementia in elderly populations 3
- Worsening of depression and suicidal thinking in depressed patients 6
- Tolerance development requiring dose escalation 7, 8
- Rebound insomnia upon discontinuation 7, 8
Advantages of Z-Drugs Over Traditional Benzodiazepines
Non-benzodiazepine benzodiazepine receptor agonists (Z-drugs) cause less disruption of normal sleep architecture than traditional benzodiazepines 9
Additional advantages include:
- Less psychomotor and memory impairment, especially compared to longer-acting benzodiazepines 9
- Rebound insomnia and withdrawal symptoms occur less frequently and are milder 9
- Lower tolerance and abuse potential for long-term use 9
- Minimal respiratory depression 9
Special Population Considerations
Elderly Patients
The elderly are especially susceptible to dose-related adverse effects and should receive the lowest available doses: 3
- First choice: Low-dose doxepin 3-6 mg (most appropriate for elderly with favorable safety profile) 3
- Avoid all traditional benzodiazepines due to increased risk of falls, cognitive impairment, respiratory depression, and dementia 4, 3
- If Z-drugs must be used: Zolpidem maximum 5 mg in elderly 2
- Never use antihistamines (OTC sleep aids) due to antimuscarinic effects and strong recommendation against use in 2019 Beers Criteria 3
Patients with Comorbid Conditions
- Depression/anxiety: Consider sedating antidepressants as second-line 1
- Substance abuse history: Avoid benzodiazepines entirely; consider ramelteon or suvorexant 2
- Respiratory disorders: Avoid benzodiazepines due to respiratory depression risk 4
- Seizure disorder or bipolar disorder: Use caution with sleep restriction in CBT-I 2
Critical Prescribing Principles When Benzodiazepines Are Used
If benzodiazepines must be prescribed (third-line only):
- Use the lowest effective dose 4, 6
- Limit duration to less than 4 weeks 4
- Administer on empty stomach to maximize effectiveness and potentially allow lower dosing 1, 4
- Avoid combination with alcohol, opioids, or other CNS depressants (significantly increases risk of complex sleep behaviors, respiratory depression, and death) 1, 6
- Implement gradual taper for discontinuation using patient-specific plan to reduce withdrawal risk 6
- Monitor regularly for adverse effects, especially during initial treatment 2
- Screen for abuse risk before prescribing and throughout treatment 6
Common Pitfalls to Avoid
- Using benzodiazepines as first-line treatment instead of CBT-I and Z-drugs 2, 3
- Prescribing long-acting benzodiazepines (e.g., flurazepam) which carry increased risk of residual daytime drowsiness without clear benefit 1
- Continuing pharmacotherapy long-term without periodic reassessment 2
- Failing to implement CBT-I alongside medication (short-term hypnotic treatment should always be supplemented with behavioral interventions) 1, 2
- Not recognizing that insomnia persisting beyond 7-10 days of treatment requires evaluation for underlying sleep disorders like sleep apnea or restless legs syndrome 2, 6
- Using multiple sedative medications simultaneously (significantly increases risks of falls, cognitive impairment, and complex sleep behaviors) 2
- Abrupt discontinuation rather than gradual taper 6
Medications NOT Recommended
The following should NOT be used for insomnia: 1, 2
- Over-the-counter antihistamines (diphenhydramine) - lack of efficacy data and safety concerns
- Herbal supplements (valerian) - insufficient evidence
- Nutritional substances (melatonin supplements) - insufficient evidence
- Trazodone - not recommended by AASM despite widespread off-label use 2
- Tiagabine - not recommended 2
- Barbiturates and chloral hydrate - not recommended due to safety concerns 1, 2
- Antipsychotics (quetiapine, olanzapine) - problematic metabolic side effects, increased mortality risk in elderly 1, 3