Can trazodone be co‑administered with eszopiclone (Lunesta)?

Can Trazodone Be Given with Lunesta (Eszopiclone)?

No, trazodone should not be combined with Lunesta (eszopiclone) for insomnia treatment because trazodone is explicitly not recommended for insomnia by major guidelines, and combining multiple sedating agents markedly increases risks of respiratory depression, cognitive impairment, falls, and complex sleep behaviors without providing meaningful additional benefit. 1, 2

Why Trazodone Should Be Avoided

• The American Academy of Sleep Medicine issues a weak recommendation against using trazodone for either sleep-onset or sleep-maintenance insomnia, based on trials showing only modest improvements (≈10 minutes reduction in sleep latency, ≈8 minutes reduction in wake after sleep onset) with no improvement in subjective sleep quality. 1, 2

• In clinical trials, adverse events occurred in ≈75% of participants on trazodone versus ≈65% on placebo, with headache in ≈30% and somnolence in ≈23%, leading guideline panels to conclude that harms outweigh minimal benefits. 1

• Trazodone lacks the robust efficacy data supporting FDA-approved hypnotics and carries significant side-effect burden without demonstrated superiority. 2

Dangers of Combining Multiple Sedating Agents

• Combining eszopiclone with trazodone creates dangerous polypharmacy that markedly increases the risk of respiratory depression, cognitive impairment, falls, fractures, and complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating). 1

• The CDC explicitly warns that using multiple CNS depressants together produces additive psychomotor impairment and substantially raises the likelihood of potentially fatal overdose. 1

• All benzodiazepine-receptor agonists (including eszopiclone) carry FDA warnings for complex sleep behaviors, and concurrent use of sedating agents amplifies that risk. 1

Evidence-Based Alternatives to This Combination

If Eszopiclone Alone Is Insufficient

First, optimize behavioral therapy:

• Initiate or verify that Cognitive Behavioral Therapy for Insomnia (CBT-I) is in place before adding or changing medication; CBT-I provides superior long-term outcomes and sustained benefits after treatment discontinuation. 1

• CBT-I includes stimulus control, sleep restriction, relaxation techniques, and cognitive restructuring, and can be delivered via individual, group, telephone, web-based, or self-help formats. 1

Second, adjust eszopiclone dosing:

• If currently taking eszopiclone 2 mg, increase to 3 mg (maximum 2 mg for adults ≥65 years) after 1–2 weeks if the lower dose is well tolerated but insufficient. 1

• Eszopiclone demonstrates moderate-to-large improvement in sleep quality and increases total sleep time by 28–57 minutes at therapeutic doses. 1, 3

Third, consider switching to an alternative agent:

• Low-dose doxepin 3–6 mg for sleep-maintenance insomnia reduces wake after sleep onset by 22–23 minutes with minimal anticholinergic effects and no abuse potential. 1

• Suvorexant 10 mg (orexin-receptor antagonist) reduces wake after sleep onset by 16–28 minutes with lower risk of cognitive and psychomotor impairment than benzodiazepine-type agents. 1, 4

• Lemborexant offers pharmacokinetic advantages over suvorexant with a similar mechanism of action and favorable tolerability profile. 1, 3

Critical Safety Monitoring

• Reassess after 1–2 weeks to evaluate sleep-onset latency, total sleep time, nocturnal awakenings, daytime functioning, and adverse effects (somnolence, bitter taste, headache, memory impairment). 1

• Screen for complex sleep behaviors at every visit; discontinue medication immediately if sleep-driving, sleep-walking, or sleep-eating occurs. 1

• FDA labeling limits eszopiclone to ≤4 weeks for acute insomnia; evidence beyond 4 weeks is limited, and long-term use requires periodic reassessment. 1, 3

• Avoid alcohol while using eszopiclone, as it markedly increases the risk of complex sleep behaviors and respiratory depression. 1

Common Pitfalls to Avoid

• Starting trazodone despite guideline recommendations against its use for insomnia leads to unnecessary side effects without meaningful benefit. 1, 2

• Combining multiple sedative agents without first optimizing monotherapy and CBT-I creates avoidable risks of respiratory depression, falls, and cognitive impairment. 1

• Failing to implement CBT-I alongside medication results in less durable benefit and higher likelihood of long-term medication dependence. 1

• Continuing pharmacotherapy long-term without periodic reassessment violates FDA labeling and guideline recommendations for short-term use. 1