Psychiatry AdvisorInsomnia Treatment: CBT-I vs Amitriptyline — Which Is Best?

This multicenter RCT demonstrates that low-dose amitriptyline (10-20mg) achieves noninferiority to CBT-I for insomnia severity reduction in medically complex patients, though CBT-I showed superior clinical response rates. The liberal 4-point noninferiority margin and absence of placebo control limit definitive efficacy conclusions, particularly given the 68% discontinuation-related sleep worsening with amitriptyline.

⚕️ Key Clinical Considerations ⚕️

• Noninferiority established but clinical response favored CBT-I: Although ISI scores met noninferiority criteria (adjusted mean difference 1.1 points, 95% CI -0.5 to 2.8), CBT-I achieved higher clinical response rates (58% vs 41%, OR 2.02, NNT=6).
• Significant anticholinergic burden with amitriptyline: Mean side-effect scores were substantially higher in the amitriptyline group (10.6 vs 7.4, p=.001), predominantly dry mouth, vivid dreams, and urinary difficulties requiring clinical monitoring.
• Discontinuation syndrome poses treatment sustainability concerns: 68% of amitriptyline users reported worsening sleep after stopping medication, with only 12% experiencing temporary effects, suggesting physiological dependence risk.
• Study limitations reduce generalizability: Liberal noninferiority margin, no placebo arm, lack of CBT-I fidelity monitoring, and mixed delivery formats (including videoconference) complicate interpretation for practice application.
• Baseline BZRA use in 30% confounds results: Concurrent benzodiazepine receptor agonist use during the trial may have influenced outcomes and complicates real-world translation for polypharmacy management.

🎯 Clinical Practice Impact 🎯

• Patient Communication: Counsel patients that while both treatments reduce insomnia severity, CBT-I offers higher likelihood of clinical response without anticholinergic side effects or discontinuation problems, though requires greater time commitment across 7 sessions.
• Practice Integration: Reserve low-dose amitriptyline for patients unable to access or complete CBT-I, monitoring closely for anticholinergic effects in elderly or cognitively vulnerable populations, and establishing discontinuation protocols.
• Risk Management: Screen for contraindications including urinary retention, cognitive impairment, and cardiac conduction abnormalities before prescribing amitriptyline; document informed consent regarding discontinuation-related sleep worsening risk.
• Neuropsychiatric Monitoring: CBT-I’s equivalent efficacy without medication burden makes it particularly appropriate for patients with dementia risk, cognitive complaints, or multiple medications where anticholinergic load matters.

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