Is it safe to add trazodone (antidepressant medication) at night?

Is It Safe to Add Trazodone at Night?

The American Academy of Sleep Medicine explicitly recommends against using trazodone for insomnia treatment, as the potential harms outweigh the limited benefits, though it may be considered when comorbid depression or specific psychiatric conditions are present. 1, 2

Safety Profile and Key Concerns

Cardiovascular and Serious Adverse Events

• Priapism occurs at an alarmingly high rate (12% in one veteran study), requiring direct questioning about this potentially serious side effect 3
• Orthostatic hypotension and cardiac arrhythmias require monitoring, particularly in elderly patients 4
• Use caution in patients with premature ventricular contractions due to potential cardiovascular effects 5

Common Side Effects

• Headache occurs in 30% of patients (versus 19% placebo) and somnolence in 23% (versus 8% placebo) 1
• Daytime drowsiness, dizziness, and psychomotor impairment affect 60% of patients continuing treatment, raising particular concern in elderly populations 6, 7
• Overall, 75% of trazodone users experience some adverse event compared to 65% on placebo 1

Evidence Against Efficacy for Insomnia

Guideline Recommendations

• The American Academy of Sleep Medicine gives trazodone a "WEAK" recommendation against its use for sleep onset or maintenance insomnia 1, 2
• The VA/DOD guidelines explicitly advise against trazodone for chronic insomnia disorder 2
• Trazodone is relegated to third-line status, only after benzodiazepine receptor agonists and ramelteon have failed 6

Clinical Trial Data

• At 50 mg dosing, trazodone reduced sleep latency by only 10.2 minutes (below clinical significance threshold) 1
• Total sleep time increased by a clinically insignificant 21.8 minutes 1
• No improvement in subjective sleep quality was demonstrated 1, 2
• Wake after sleep onset decreased by only 7.7 minutes (below threshold) 1

When Trazodone May Be Appropriate

Specific Clinical Scenarios

• Comorbid depression with insomnia, where antidepressant properties provide dual benefit 2, 8
• Agitation in dementia as an alternative to antipsychotics (25 mg initial dose, maximum 200-400 mg/day in divided doses) 5
• PTSD-associated nightmares, where it reduced nightmare frequency from 3.3 to 1.3 nights/week at mean dose of 212 mg/day 5, 3

Dosing Considerations for Safety

• For insomnia, use lower doses (25-100 mg) rather than antidepressant doses 5
• FDA-approved antidepressant dosing starts at 150 mg/day in divided doses, with maximum outpatient dose of 400 mg/day 9
• Administer shortly after a meal or light snack to optimize absorption and tolerability 9
• When discontinuing, taper gradually rather than stopping abruptly to avoid withdrawal symptoms 9

Preferred Alternatives for Insomnia

First-Line Treatment

• Cognitive Behavioral Therapy for Insomnia (CBT-I) should be the initial treatment approach 2, 6

Second-Line Pharmacological Options

• Zolpidem 10 mg (5 mg in elderly) for sleep onset 6
• Eszopiclone 2-3 mg for both sleep onset and maintenance 2, 6
• Ramelteon for sleep onset insomnia 2
• Doxepin 3-6 mg for sleep maintenance insomnia 2

Critical Caveats

Drug Interactions

• Allow at least 14 days between discontinuing MAOIs and starting trazodone, and vice versa 9
• Consider dose reduction when coadministered with strong CYP3A4 inhibitors 9
• Exercise caution with concurrent sedating medications due to additive effects 2

Monitoring Requirements

• Screen for personal or family history of bipolar disorder before initiating treatment 9
• Directly ask about priapism at follow-up visits 3
• Monitor for orthostatic hypotension, particularly in elderly patients 6, 4
• Regular follow-up to assess effectiveness, side effects, and ongoing need for therapy 2, 6

Special Populations

• Trazodone has minimal anticholinergic activity compared to tricyclic antidepressants, potentially making it better tolerated in elderly patients for depression 5
• However, elderly patients remain at higher risk for falls, dizziness, and psychomotor impairment 7