What is the recommended dosing of trazodone for insomnia, including safety considerations and alternative treatments?

Trazodone for Insomnia: Evidence-Based Recommendations

Primary Recommendation

The U.S. Department of Veterans Affairs/Department of Defense and the American Academy of Sleep Medicine explicitly advise against using trazodone for chronic insomnia disorder because the low-quality evidence supporting its efficacy is outweighed by its adverse effect profile. 1, 2

Evidence Against Trazodone

Lack of Objective Efficacy

• A systematic review found no differences in sleep efficiency, sleep onset latency, total sleep time, or wake after sleep onset between trazodone (50-150 mg) and placebo in patients with chronic insomnia 1
• While trazodone showed modest improvement in subjective sleep quality only, this single benefit does not justify its use given the adverse effect profile 1
• The studies supporting trazodone had severe limitations: very short treatment durations (mean 1.7 weeks) and follow-up of only 1-4 weeks 1

Adverse Effects That Outweigh Benefits

• Trazodone causes daytime drowsiness, dizziness, and psychomotor impairment, particularly concerning in elderly patients 2
• Risk of priapism, which has led to treatment discontinuation in clinical studies 2
• Risk of orthostatic hypotension and cardiac arrhythmias 3
• The adverse effect profile is dose-dependent, with drowsiness being the most common side effect 4

Recommended Treatment Algorithm

First-Line: Non-Pharmacologic Treatment

Cognitive Behavioral Therapy for Insomnia (CBT-I) must be offered as initial treatment before any medication, demonstrating superior long-term efficacy with sustained benefits after discontinuation 1, 2

CBT-I components include: 1, 2

• Stimulus control therapy
• Sleep restriction therapy
• Relaxation techniques
• Cognitive restructuring

Second-Line: FDA-Approved Pharmacotherapy

If CBT-I is insufficient or unavailable, use FDA-approved medications in this order:

For Sleep Onset and Maintenance Insomnia:

• Eszopiclone 2-3 mg (1 mg in elderly or severe hepatic impairment) 1, 2
• Zolpidem 10 mg (5 mg in elderly) 1, 2

For Sleep Onset Only:

• Zaleplon 10 mg 1, 2
• Ramelteon 8 mg (preferred for patients with substance use history due to zero addiction potential) 1, 2

For Sleep Maintenance Only:

• Low-dose doxepin 3-6 mg (most effective for sleep maintenance with minimal side effects and no abuse potential) 1, 2
• Suvorexant (orexin receptor antagonist) 2

Third-Line: When First and Second-Line Fail

Trazodone may only be considered as a third-line agent when:

• Comorbid major depression is present requiring full-dose antidepressant treatment (though low doses used for insomnia [25-50 mg] are inadequate for treating depression) 2
• First and second-line treatments have failed 2
• The patient is already on a full-dose antidepressant and needs additional sleep support 2

Trazodone Dosing (If Used Despite Recommendations)

If trazodone is prescribed despite guideline recommendations against it:

• Typical dosing range: 25-150 mg at bedtime 1, 4
• Most effective dose: 25-75 mg (lower doses showed higher response rates than 100-150 mg in retrospective studies) 5
• Timing: Administer at least 1 hour before bedtime (earlier than hypnotics) due to slower onset of action 6
• Administration: On an empty stomach to maximize effectiveness 2

Critical Safety Considerations

Mandatory Patient Counseling

Before prescribing any sleep medication, counsel patients about: 1, 2

• Treatment goals and realistic expectations
• Potential side effects and safety concerns
• Risk of complex sleep behaviors (sleepwalking, sleep-driving)
• Importance of allowing 7-8 hours of sleep time
• Avoiding alcohol and other sedatives

Monitoring Requirements

• Assess effectiveness after 1-2 weeks 2
• Use the lowest effective dose for the shortest duration possible 1, 2
• Regular follow-up to evaluate continued need for medication 1, 2
• Screen for complex sleep behaviors and discontinue immediately if observed 2

Special Populations

• Elderly patients: Require dose reduction and face increased fall risk with trazodone 2
• Hepatic/renal impairment: Use with caution and consider dose reduction 2
• Pregnancy/nursing: Avoid trazodone 2
• Respiratory compromise: Use extreme caution 2

Medications to Explicitly Avoid

Do not use for primary insomnia: 1, 2

• Benzodiazepines (lorazepam, temazepam, clonazepam) - higher dependency risk, falls, cognitive impairment
• Antihistamines (diphenhydramine) - no efficacy data, anticholinergic burden, tolerance after 3-4 days
• Antipsychotics (quetiapine, olanzapine) - insufficient evidence, significant metabolic side effects
• Herbal supplements (valerian, kava, chamomile) - no proven efficacy

Common Pitfalls to Avoid

• Never use trazodone as first-line therapy for primary insomnia 2
• Never prescribe trazodone without attempting CBT-I or FDA-approved hypnotics first 2
• Never combine two sedating medications without clear justification and close monitoring 2, 7
• Never use doses above 150 mg for insomnia (higher doses show worse response rates) 5
• Never assume trazodone is "safer" than FDA-approved hypnotics - the evidence does not support this 1

Why Trazodone Remains Commonly Prescribed Despite Evidence

While trazodone's off-label use for insomnia has surpassed its use as an antidepressant in clinical practice 4, this widespread use is not supported by high-quality evidence. The 2019 VA/DOD guidelines and American Academy of Sleep Medicine recommendations represent the most current, authoritative guidance and explicitly advise against its use for chronic insomnia 1, 2.