Can trazodone be combined with ramelteon (Rozerem) for sleep?

Combining Trazodone with Ramelteon for Sleep

Yes, trazodone can be combined with ramelteon for insomnia, though this combination is not ideal and should only be considered after better-supported options have failed. 1, 2

Evidence-Based Treatment Hierarchy

The American Academy of Sleep Medicine explicitly recommends combining a benzodiazepine receptor agonist (BzRA) or ramelteon with a sedating antidepressant when initial treatments are unsuccessful. 1 However, trazodone specifically is recommended AGAINST for insomnia treatment by both the American Academy of Sleep Medicine and VA/DOD guidelines, even as monotherapy. 2, 3

Why This Combination Is Problematic

• Trazodone lacks evidence for insomnia: The American Academy of Sleep Medicine gave trazodone a "WEAK" recommendation against its use, finding that benefits do not outweigh potential harms at the studied 50mg dose. 2
• Clinical trials showed only modest improvements in sleep parameters with no significant improvement in subjective sleep quality compared to placebo. 2, 3
• Ramelteon is appropriate: It is FDA-approved for sleep onset insomnia and recommended by guidelines at 8mg taken 30 minutes before bedtime. 1, 4, 5

When This Combination Might Be Considered

If you proceed with this combination, it should only be after:

• Cognitive Behavioral Therapy for Insomnia (CBT-I) has been attempted as first-line treatment 2, 3
• Second-line options have failed, including:
  • Eszopiclone 2-3mg, zolpidem 10mg, or temazepam 15mg for sleep onset and maintenance 2
  • Zaleplon 10mg or ramelteon 8mg alone for sleep onset 2
  • Suvorexant or doxepin 3-6mg for sleep maintenance 2

The combination may have clinical rationale when:

• Comorbid depression is present (though low-dose trazodone used for insomnia is inadequate for treating major depression) 2
• The patient has already been on trazodone and adding ramelteon is being considered 1

Preferred Alternative: Doxepin + Ramelteon

A superior combination supported by guidelines is doxepin 3-6mg with ramelteon 8mg. 1 This pairing:

• Targets different insomnia mechanisms: ramelteon for sleep onset, doxepin for sleep maintenance 1
• Has FDA approval for doxepin at low doses (3mg and 6mg) with minimal side effects 1
• Is explicitly mentioned by the American Academy of Sleep Medicine as an appropriate combination 1

Safety Monitoring for Trazodone + Ramelteon

If this combination is used, monitor closely for:

• Additive sedation effects: Both medications cause sedation, requiring close monitoring 1, 2
• Trazodone-specific risks:
  • Daytime drowsiness and dizziness (particularly in elderly patients) 2
  • Orthostatic hypotension 6
  • Priapism (rare but serious) 2
  • QTc prolongation 3
• Avoid alcohol: It has additive effects on sedation and psychomotor performance 1

Dosing Recommendations

• Ramelteon: 8mg taken 30 minutes before bedtime 1, 4
• Trazodone: If used, start at 25-50mg (though evidence is based on 50mg dosing) 2
• Use the lowest effective doses to minimize side effects 1, 2
• Administer on an empty stomach to maximize effectiveness 2

Important Caveats

• Regular follow-up is essential to assess effectiveness, side effects, and ongoing need for both medications 1, 2
• Attempt tapering when conditions allow per American Academy of Sleep Medicine recommendations 1
• Elderly patients require dose reduction and extra caution with trazodone 2
• Avoid in pregnancy and nursing (trazodone) 2
• Exercise caution with compromised respiratory function, hepatic or heart failure 2