Which is better for sleep, melatonin or trazodone (an antidepressant)?

Melatonin vs. Trazodone for Sleep: Evidence-Based Comparison

Melatonin is preferable to trazodone for sleep disorders due to its better safety profile, despite trazodone showing slightly greater efficacy in some studies. 1, 2

Efficacy Comparison

Trazodone

• Trazodone shows greater improvement in sleep quality compared to melatonin, with significant reductions in Pittsburgh Sleep Quality Index scores in psychiatric patients (mean decrease = 7.0) 2
• However, the American Academy of Sleep Medicine recommends against using trazodone for sleep onset or maintenance insomnia in adults, based on trials of 50 mg doses 1
• Clinical trials showed that trazodone 50 mg produced only modest improvements in sleep parameters compared to placebo, with no improvement in subjective sleep quality 1
• The Department of Veterans Affairs/Department of Defense (VA/DOD) guidelines explicitly advise against the use of trazodone for chronic insomnia disorder 1

Melatonin

• Melatonin has both hypnotic and sleep/wake rhythm regulating properties that are demonstrable in healthy humans 3
• It is particularly useful for circadian rhythm sleep disorders like delayed sleep phase syndrome, jet lag, and shift-work sleep disorder 3
• While slightly less effective than trazodone in improving sleep quality (PSQI reduction = 6.1 vs. 7.0 for trazodone), melatonin significantly reduces daytime drowsiness 2
• Meta-analyses have revealed that melatonin is not sufficiently effective in treating most primary sleep disorders, partly due to its extremely short half-life in circulation 3

Safety Profile Comparison

Trazodone Side Effects

• Trazodone is associated with frequent adverse effects, including morning grogginess (15%) and orthostatic hypotension (10%) 2
• Other adverse effects include daytime drowsiness, dizziness, and psychomotor impairment, which are particularly concerning for elderly patients 1
• More serious risks include priapism, orthostatic hypotension, and cardiac arrhythmias 4
• The benefits of trazodone for sleep do not outweigh the potential harms according to the American Academy of Sleep Medicine guideline 1

Melatonin Safety Advantages

• Melatonin has the fewest adverse effects compared to trazodone, including the lowest rates of morning grogginess (5%) and dizziness (10%) 2
• Unlike many sleep-promoting compounds, melatonin does not cause hangover nor withdrawal effects and is devoid of any addictive potential 3
• In a hospital study comparing the two medications, melatonin showed a lower rate of patients needing additional sleep aids (19.7% vs. 34.6% for trazodone) 5

Special Populations

Elderly Patients

• Elderly patients are at higher risk for adverse effects from sedative-hypnotics, including trazodone 4
• Low nocturnal melatonin production and secretion have been documented in elderly insomniacs, and exogenous melatonin has been shown to be beneficial in treating sleep disturbances in these patients 3

Patients with Dementia

• For patients with dementia and sleep disturbances, low-certainty evidence suggests that trazodone 50 mg may improve total nocturnal sleep time (42.46 minutes increase) and sleep efficiency (8.53% improvement) 6
• However, there is low-certainty evidence that melatonin doses up to 10 mg may have little or no effect on major sleep outcomes in people with Alzheimer's disease and sleep disturbances 6

Clinical Decision Algorithm

1. First-line approach: Cognitive behavioral therapy for insomnia (CBT-I) should be the first-line treatment for chronic insomnia 1

2. If pharmacological intervention is needed:

   • For patients with circadian rhythm disorders: Choose melatonin 3
   • For patients with primary insomnia without comorbidities: Choose melatonin due to better safety profile 1, 2
   • For patients with comorbid depression: Consider trazodone only if benefits outweigh risks 1
   • For elderly patients or those at risk for falls: Strongly prefer melatonin over trazodone 4, 1

3. Dosing considerations:

   • Melatonin: Start with 1-3 mg taken 1-2 hours before bedtime 3
   • Trazodone (if used despite recommendations against it): Lower doses (25-50 mg) are typically employed for insomnia, which are below the therapeutic antidepressant range 1

Important Caveats

• The American College of Physicians recommends that clinicians use a shared decision-making approach when considering pharmacological therapy for chronic insomnia disorder in whom cognitive behavioral therapy for insomnia alone was unsuccessful 4
• Benzodiazepines and newer generation nonbenzodiazepine benzodiazepine receptor agonists (e.g., zolpidem, zaleplon, eszopiclone) have shorter half-lives and fewer overall side effects than trazodone, but high-quality data to support their use with demented older adults are nonexistent 4
• All hypnotic medications should be administered at the lowest effective dose and for the shortest possible duration 1