What can be done to address early morning wakefulness in patients taking Trazodone (triazolopyridine antidepressant)?

Addressing Early Morning Wakefulness with Trazodone

Discontinue trazodone and switch to an evidence-based treatment, as trazodone is not recommended for insomnia and does not effectively address sleep maintenance problems like early morning awakening. 1, 2

Why Trazodone Fails for Early Morning Awakening

The American Academy of Sleep Medicine explicitly recommends against using trazodone for either sleep onset or sleep maintenance insomnia. 1 The evidence is clear:

• Trazodone 50 mg reduces wake after sleep onset by only 7.7 minutes—falling well below the clinical significance threshold 1
• Total sleep time increases by only 21.8 minutes, which is clinically insignificant 1
• Sleep quality improvement is negligible (−0.13 points on a 4-point scale) 1
• Number of awakenings decreases by only 0.4, less than the 0.5 awakening threshold for clinical significance 1

The overall quality of evidence is moderate to very low, and the task force judged that harms potentially outweigh benefits given the absence of demonstrated efficacy. 1

Adverse Effects That Make the Problem Worse

Trazodone causes significant side effects that can worsen sleep quality: 1

• 75% of patients experience adverse events (versus 65.4% on placebo)
• Headache occurs in 30% (versus 19% placebo)
• Somnolence affects 23% (versus 8% placebo), which can paradoxically disrupt sleep architecture
• In elderly patients, orthostatic hypotension and falls are additional serious concerns 2, 3

Evidence-Based Alternatives for Sleep Maintenance Insomnia

First-Line Treatment

Cognitive behavioral therapy for insomnia (CBT-I) should be the initial treatment as it is recommended by major guidelines for chronic insomnia disorder. 2

Pharmacologic Options for Sleep Maintenance

For patients requiring medication specifically for sleep maintenance problems (like early morning awakening):

• Suvorexant is recommended for sleep maintenance insomnia 2
• Doxepin (3-6 mg) has weak evidence for efficacy in treating sleep maintenance insomnia, with minimal adverse events in excess of placebo 1
• Zolpidem extended-release has been studied for sleep maintenance with some benefit 1

What NOT to Do

Do not increase the trazodone dose—higher doses lack guideline support for insomnia and increase adverse event risk. 2, 4 The evidence base is limited to 50 mg, and doses used for depression (150-400 mg) are not validated for insomnia treatment. 5, 6

Avoid these common mistakes: 2

• Do not prescribe benzodiazepines (dependency, falls, cognitive impairment, respiratory depression risk)
• Do not use antihistamines (tolerance develops in 3-4 days, antimuscarinic effects)
• Do not use antipsychotics like quetiapine (sparse evidence, serious harms including mortality risk in elderly)

Clinical Implementation Strategy

1. Discontinue trazodone after discussing with the patient that it lacks evidence for their specific problem 1, 2

2. Initiate CBT-I as first-line therapy, which addresses the underlying sleep maintenance issue 2

3. If pharmacotherapy is needed, select based on the specific sleep complaint:

   • For early morning awakening specifically: Consider suvorexant or low-dose doxepin (3-6 mg) 1, 2
   • Prescribe at the lowest effective dose for the shortest duration 2

4. Monitor for FDA-warned serious injuries from sleep behaviors (sleepwalking, sleep driving) with non-benzodiazepine hypnotics 2

Important Caveats

Cardiovascular considerations: If the patient has cardiovascular conditions, this provides additional rationale to discontinue trazodone, as it requires careful monitoring and can cause QT prolongation. 2, 7, 3

Polypharmacy in elderly: Adding medications rather than switching increases fall risk and drug interactions—always substitute rather than add. 2

Withdrawal management: Do not abruptly stop trazodone; taper to avoid withdrawal symptoms including anxiety, agitation, and paradoxically worsened sleep problems. 7