Hydroxyzine vs. Trazodone for Insomnia Treatment
Neither hydroxyzine nor trazodone should be used as first-line treatments for insomnia, as both are explicitly advised against in current clinical guidelines due to limited efficacy evidence and concerning side effect profiles. 1, 2
Guideline Recommendations Against Both Medications
- The Department of Veterans Affairs/Department of Defense (VA/DOD) clinical practice guidelines explicitly advise against using trazodone for chronic insomnia disorder due to its adverse effect profile outweighing its limited benefits 1
- Similarly, the VA/DOD guidelines recommend against using antihistamines (including hydroxyzine) for chronic insomnia disorder, noting that tolerance to sedative effects develops after just 3-4 days of continuous use 1
- The American Academy of Sleep Medicine gives a "WEAK" recommendation against trazodone use for both sleep onset and maintenance insomnia 2, 3
Comparative Efficacy
Trazodone
- Systematic reviews found no significant differences in sleep efficiency between trazodone (50-150mg) and placebo in patients with chronic insomnia 1
- While trazodone showed modest improvement in subjective sleep quality, there were no significant differences in sleep onset latency, total sleep time, or wake time after sleep onset compared to placebo 1, 2
- Trazodone may be more effective for sleep maintenance insomnia than for sleep onset insomnia 4
- In a small preliminary study, trazodone significantly lengthened total sleep time and decreased cortisol levels compared to CBT-I in patients with insomnia and short sleep duration 5
Hydroxyzine (Antihistamine)
- No studies meeting inclusion criteria were identified for antihistamines as interventions for chronic insomnia disorder in the VA/DOD guideline review 1
- Tolerance to the sedative effects of antihistamines develops after just 3-4 days of continuous use, limiting their benefit even for short-term treatment 1
- The 2019 Beers Criteria strongly recommend avoiding antihistamines in older adults due to their antimuscarinic adverse effect profile 1
Side Effect Profiles
Trazodone
- Common side effects include daytime drowsiness, dizziness, and psychomotor impairment 2, 6
- More serious side effects include priapism, which has led to treatment discontinuation in clinical studies 2, 6
- Side effects are dose-dependent, with drowsiness being the most common 7
Hydroxyzine (Antihistamine)
- Antihistamines have significant antimuscarinic side effects, particularly problematic in older adults 1
- Side effects include dry mouth, blurred vision, urinary retention, constipation, and cognitive impairment 1
- Rapid development of tolerance limits even short-term efficacy 1
Recommended First-Line Treatments for Insomnia
- Cognitive behavioral therapy for insomnia (CBT-I) should be the first-line treatment for chronic insomnia 2, 3
- If pharmacotherapy is needed, the following are recommended based on evidence:
Important Clinical Considerations
- All hypnotic medications should be used at the lowest effective dose and for the shortest possible duration 2, 3
- Patients should be counseled about potential risks including sleep behaviors (sleepwalking, sleep driving) associated with sedative medications 2
- Regular follow-up is essential to assess medication effectiveness, side effects, and the ongoing need for pharmacotherapy 2
- When trazodone is used for insomnia (despite recommendations against it), lower doses (25-50mg) are typically employed, which are below the therapeutic antidepressant range 2
Special Circumstances
- Trazodone may have some utility in specific clinical scenarios not addressed by insomnia guidelines, such as when comorbid depression is present 2, 4
- Trazodone increases the duration of deep sleep, which may be beneficial for sleep quality in some patients, while hypnotics typically decrease slow-wave activity 4