What can be added to trazodone (an antidepressant) for a patient already taking it, to help maintain sleep?

Adding Medication to Trazodone for Sleep Maintenance

Do not add another medication to trazodone for sleep maintenance—instead, discontinue trazodone and switch to a first-line agent like doxepin 3-6 mg, eszopiclone 2-3 mg, or suvorexant 10-20 mg, as the American Academy of Sleep Medicine explicitly recommends against using trazodone for nocturnal awakenings because the benefits do not outweigh the risks. 1

Why Trazodone Should Not Be Used for Sleep Maintenance

The evidence against trazodone for nocturnal awakenings is compelling:

• Trazodone at 50 mg reduces wake time after sleep onset by only 7.7 minutes compared to placebo—a clinically insignificant improvement 1
• Total sleep time increases by only 21.8 minutes, which is not clinically meaningful 1
• The number of awakenings decreases by only 0.4 (below the threshold of 0.5 for clinical significance) 1
• Subjective sleep quality does not improve compared to placebo 1, 2
• 75% of patients on trazodone report adverse effects versus 65.4% on placebo 1

Specific Risks That Outweigh Benefits

• Headaches occur in 30% of patients (versus 19% with placebo) 1
• Daytime somnolence affects 23% (versus 8% with placebo) 1
• Orthostatic hypotension, particularly dangerous in elderly patients 1, 3
• Cardiac arrhythmias and QTc prolongation 4, 3
• Rare but serious priapism 2, 4

The Correct Treatment Algorithm

First-Line: Non-Pharmacologic Treatment

• Cognitive Behavioral Therapy for Insomnia (CBT-I) should be attempted first, including stimulus control therapy, sleep restriction therapy, and relaxation techniques 2, 5

Second-Line: FDA-Approved Medications for Sleep Maintenance

For nocturnal awakenings specifically, the American Academy of Sleep Medicine recommends: 1, 2

• Doxepin 3-6 mg at bedtime (particularly suitable for sleep maintenance due to targeted efficacy and favorable side effect profile at low doses) 1
• Eszopiclone 2-3 mg at bedtime 1, 2
• Suvorexant 10-20 mg at bedtime 1, 2
• Temazepam 15 mg at bedtime 1, 2
• Zolpidem 10 mg at bedtime 1, 2

Why Not Combine Medications?

Combining trazodone with another sedating medication is explicitly contraindicated due to: 5

• Risk of serotonin syndrome 4
• Excessive sedation 5
• Additive QTc prolongation 5
• Increased fall risk, especially in elderly patients 1, 3

When Trazodone Might Be Considered (Third-Line Only)

Trazodone should only be considered as a third-line agent in these specific scenarios: 2, 5

• Comorbid depression is present (though 50 mg is insufficient for treating major depression—therapeutic antidepressant doses are higher) 2, 5
• All first-line and second-line treatments have failed or are contraindicated 2, 5
• The patient can be combined with a full-dose antidepressant if depression and insomnia coexist 5

Critical Safety Warnings When Switching Medications

Contraindications to Monitor:

• Do not start new medication if patient stopped an MAOI within the last 2 weeks 4
• Avoid in patients with cardiac disease, QT prolongation, or family history of QT prolongation 4
• Use extreme caution in elderly patients due to orthostatic hypotension and fall risk 1, 4
• Avoid in pregnancy and breastfeeding 5, 4

Drug Interactions to Check:

When switching from trazodone, review for interactions with: 4

• SSRIs, SNRIs, or other serotonergic agents
• Anticoagulants (warfarin, aspirin, NSAIDs)
• Antiarrhythmics or other QT-prolonging drugs
• Phenytoin or other enzyme-inducing medications

Practical Implementation

Step 1: Discontinue trazodone gradually to avoid withdrawal symptoms (anxiety, agitation, sleep problems) 2

Step 2: Select appropriate first-line agent based on patient factors:

• Doxepin 3-6 mg if primary concern is sleep maintenance with minimal next-day effects 1
• Eszopiclone 2-3 mg if both sleep onset and maintenance are problematic 1, 2
• Suvorexant 10-20 mg for pure sleep maintenance issues 1, 2

Step 3: Provide mandatory patient education: 2, 5

• Take medication shortly after a meal or light snack 4
• Allow 7-8 hours for sleep 5
• Avoid alcohol and other sedating medications 4
• Report daytime drowsiness, dizziness, or other adverse effects 2

Step 4: Follow-up assessment every few weeks initially to monitor effectiveness and adverse effects 2, 5