Doxepin vs. Hydroxyzine (Atarax) for Sleep
Low-dose doxepin (3-6 mg) is more effective than hydroxyzine for sleep maintenance insomnia, with significant improvements in wake after sleep onset, total sleep time, and sleep efficiency, while hydroxyzine may be more suitable for sleep onset insomnia. 1, 2, 3
Efficacy Comparison
Doxepin
- Low-dose doxepin (3-6 mg) significantly improves sleep maintenance parameters, with wake after sleep onset (WASO) reduced by 22-23 minutes compared to placebo 1, 3
- Total sleep time increases by 26-32 minutes with doxepin 3-6 mg 1, 2
- Sleep efficiency improves by approximately 6-7% 3
- Doxepin shows small-to-moderate improvements in sleep quality 1
- Less effective for sleep onset issues, with minimal improvement in sleep latency at 3 mg (-2.30 min) and modest improvement at 6 mg (-5.29 min) 3
Hydroxyzine (Atarax)
- Acts primarily as an antihistamine with sedative properties 4
- Clinical effects typically begin within 15-30 minutes after oral administration, making it potentially more suitable for sleep onset insomnia 4
- Limited specific data on sleep parameters compared to doxepin in the provided evidence
Mechanism of Action
- Doxepin at low doses (3-6 mg) acts primarily as a selective H1 receptor antagonist, promoting sleep initiation and maintenance 5, 6
- Hydroxyzine is an antihistamine that suppresses activity in key regions of the subcortical area of the central nervous system 4
- Both medications have antihistaminic effects, but doxepin at low doses has more specific H1 receptor selectivity 5, 6
Safety Profile
- Low-dose doxepin (3-6 mg) has a safety profile comparable to placebo in clinical trials, with only mild increases in somnolence at the 6 mg dose 2
- Higher doses of doxepin (25-300 mg) can cause significant anticholinergic and antinoradrenergic side effects 6
- Most common side effects with doxepin include headache and somnolence 7
- Hydroxyzine has minimal effects on gastric secretion and in most cases has mild antisecretory activity 4
- In a comparative study, doxepin had a higher rate of treatment adverse events (23.3%) compared to zolpidem (13.3%) 8
Clinical Considerations
When to Choose Doxepin
- For patients with sleep maintenance insomnia (difficulty staying asleep) 1, 2, 3
- When cognitive function improvement is a priority (doxepin showed better improvement in executive function compared to zolpidem) 8
- For elderly patients, starting with the lowest effective dose (3 mg) 3
When to Choose Hydroxyzine
- For patients with primary sleep onset insomnia (difficulty falling asleep) 4
- When a faster onset of action is needed (effects within 15-30 minutes) 4
Dosing Recommendations
- Doxepin: 3-6 mg administered 30 minutes before bedtime on an empty stomach 3
- The dose for insomnia (3-6 mg) is significantly lower than doses used for depression (25-150 mg) 3, 9
- Hydroxyzine: Specific dosing for insomnia not provided in the evidence, but clinical effects typically begin within 15-30 minutes after oral administration 4
Common Pitfalls to Avoid
- Failing to distinguish between sleep maintenance insomnia (where doxepin excels) versus sleep onset insomnia (where doxepin has limited efficacy) 3
- Using higher doses of doxepin (>6 mg) for insomnia, which increases risk of anticholinergic side effects without additional benefit 6
- Not considering potential rebound insomnia with doxepin discontinuation, which was observed in some patients 10
- Overlooking doxepin's contraindications, including hypersensitivity to the drug and potential cross-sensitivity with other dibenzoxepines 9