What is more effective for insomnia, trazodone or zopiclone?

Zopiclone is Superior to Trazodone for Insomnia Treatment

For insomnia treatment, zopiclone (a nonbenzodiazepine benzodiazepine receptor agonist) is the better choice over trazodone, as major clinical guidelines explicitly advise against using trazodone for chronic insomnia disorder while supporting the use of nonbenzodiazepine BZRAs like zopiclone as appropriate second-line pharmacotherapy when cognitive behavioral therapy is unavailable or unsuccessful. 1, 2

Evidence Supporting Zopiclone

Demonstrated Efficacy

• Zopiclone improves multiple objective sleep parameters including sleep efficiency, sleep onset latency, sleep quality, total sleep time, and wake after sleep onset compared to placebo 1
• The benefits of nonbenzodiazepine BZRAs (including zopiclone) outweigh potential harms according to systematic review evidence 1
• Eszopiclone (the S-enantiomer of zopiclone) demonstrates improvements of 28-57 minutes in total sleep time and 10-14 minute reductions in wake time after sleep onset 2

Guideline Support

• The VA/DOD 2019 guidelines consider offering nonbenzodiazepine BZRAs as appropriate pharmacotherapy for patients unable or unwilling to receive CBT-I 1
• These agents should be prescribed at the lowest effective dose for the shortest possible duration 1, 2

Evidence Against Trazodone

Lack of Efficacy

• The VA/DOD guidelines explicitly advise AGAINST using trazodone for treatment of chronic insomnia disorder 1, 2, 3
• Systematic reviews found no differences between trazodone (50-150 mg) and placebo in sleep efficiency, sleep onset latency, total sleep time, or wake after sleep onset 1, 3
• While trazodone showed modest improvement in subjective sleep quality, this single benefit does not outweigh its limitations 1, 3

Adverse Effect Profile

• Trazodone causes daytime drowsiness, dizziness, and psychomotor impairment, particularly concerning in elderly patients 3, 4
• Studies demonstrate significant impairments in short-term memory, verbal learning, equilibrium, and arm muscle endurance with trazodone 50 mg 4
• The adverse effect profile substantially outweighs the limited benefits 1, 3
• Evidence quality supporting trazodone is very low, with studies of very short duration (mean 1.7 weeks) 1, 5

Guideline Classification

• The American Academy of Sleep Medicine classifies trazodone as a third-line option only, reserved for cases where first and second-line treatments have failed or when comorbid depression exists 2, 3
• Trazodone at low doses (25-50 mg) used for insomnia are inadequate for treating major depression, limiting its utility even in comorbid cases 3

Critical Safety Considerations for Zopiclone

FDA Safety Warning

• The FDA issued a safety announcement regarding serious injuries from complex sleep behaviors (sleepwalking, sleep driving, engaging in activities while not fully awake) with nonbenzodiazepine BZRAs 1, 2
• All patients prescribed zopiclone must be counseled on these potential risks 1, 2

Prescribing Parameters

• Use the lowest effective dose 1, 2
• Prescribe for the shortest possible duration 1, 2
• Elderly patients require downward dosage adjustment 2
• Exercise extreme caution in patients with respiratory compromise, hepatic disease, or depression 2

Treatment Algorithm

First-Line Treatment

• Cognitive Behavioral Therapy for Insomnia (CBT-I) should be offered initially before any pharmacotherapy, as it has superior long-term outcomes with fewer adverse effects than medications 1, 2, 3

Second-Line Pharmacotherapy (When CBT-I Unavailable/Unsuccessful)

• Nonbenzodiazepine BZRAs (including zopiclone) or low-dose doxepin (3-6 mg) are appropriate options 1, 2
• Zopiclone is effective for both sleep onset and sleep maintenance insomnia 2

What to Avoid

• Do not use trazodone as first or second-line treatment for insomnia 1, 2, 3
• Avoid benzodiazepines due to dependency risk, falls, cognitive impairment, and respiratory depression 1
• Do not combine multiple sedative agents due to additive psychomotor impairment and increased fall risk 2

Common Pitfalls to Avoid

• Do not prescribe trazodone based solely on its widespread off-label use—this practice is not supported by evidence and contradicts current guidelines 1, 2, 3, 5
• Avoid using trazodone in elderly patients where cognitive and motor impairments pose significant fall risk 3, 4
• Do not assume lower doses of trazodone (25 mg) are safer or more effective—they have not been systematically studied and would likely provide even less benefit than the already insufficient 50 mg dose 3
• Remember that trazodone may only be considered when comorbid major depression requiring full antidepressant dosing is present, not for insomnia alone 2, 3