Can you take melatonin with trazodone (an antidepressant medication)?

Taking Melatonin with Trazodone for Sleep

Taking melatonin with trazodone is generally not recommended due to the potential for additive central nervous system (CNS) depressant effects, limited evidence of improved efficacy, and the fact that neither agent is strongly recommended as a first-line treatment for insomnia. 1

Safety Concerns with Combination Therapy

Potential Interactions

• Both medications have sedating properties that may compound when taken together
• Potential for increased morning grogginess, daytime drowsiness, and psychomotor impairment
• Risk of additive CNS depression when combined with other sedatives or alcohol

Evidence on Individual Medications

1. Trazodone:

   • Not FDA approved for insomnia despite widespread off-label use 1
   • Clinical guidelines specifically recommend against using trazodone for sleep onset or maintenance insomnia 1
   • Associated with cognitive and psychomotor impairments including:
     • Short-term memory deficits
     • Verbal learning difficulties
     • Impaired equilibrium
     • Reduced muscle endurance 2
   • Side effects include morning grogginess (15%) and orthostatic hypotension (10%) 3

2. Melatonin:

   • Not recommended for treating sleep onset or maintenance insomnia in adults 1
   • Limited efficacy data with only small improvements in sleep latency (9 minutes better than placebo) 1
   • Generally has fewer adverse effects than trazodone 3, 4
   • Has been associated with depressive symptoms in some patients 1

Better Alternatives for Insomnia Treatment

According to clinical guidelines, the recommended sequence for treating chronic insomnia is:

1. First-line options:

   • Cognitive Behavioral Therapy for Insomnia (CBT-I) 1
   • Short-to-intermediate acting benzodiazepine receptor agonists (BzRAs) such as zolpidem, eszopiclone, or zaleplon 1
   • Ramelteon (for sleep onset insomnia) 1

2. Second-line options:

   • Low-dose doxepin (3-6 mg) for sleep maintenance 1, 5
   • Suvorexant for sleep maintenance 1, 5

Important Clinical Considerations

• If you're currently taking trazodone for depression, adding melatonin specifically for sleep is not supported by evidence 1
• Both medications individually have limited efficacy for insomnia compared to recommended alternatives 1
• The combination has not been specifically studied in clinical trials for efficacy or safety 1
• Elderly patients should be particularly cautious with either medication due to increased sensitivity to CNS effects 1, 5

Conclusion

Rather than combining melatonin with trazodone, patients with insomnia should discuss FDA-approved treatment options with their healthcare provider. If medication is needed, evidence supports using agents like zolpidem, eszopiclone, zaleplon, ramelteon, low-dose doxepin, or suvorexant based on whether the primary issue is sleep onset or maintenance insomnia.