In an adult patient in New Zealand with insomnia unresponsive to therapeutic trials of zopiclone and low‑dose quetiapine, what next pharmacologic agent(s) can be prescribed?

Next-Line Pharmacotherapy After Zopiclone and Quetiapine Failure

Eszopiclone 2–3 mg nightly is the recommended next-line agent for this patient, as it represents a first-line benzodiazepine receptor agonist with proven efficacy for both sleep onset and maintenance insomnia, and should be initiated alongside Cognitive Behavioural Therapy for Insomnia (CBT-I). 1

Why Eszopiclone Is the Optimal Choice

• Eszopiclone demonstrates moderate-to-high quality evidence showing a 19-minute reduction in sleep-onset latency and a 45-minute increase in total sleep time compared with placebo, with 50% of patients achieving remission (Insomnia Severity Index <7) at 12 weeks versus 19% on placebo. 1

• The American Academy of Sleep Medicine explicitly recommends eszopiclone 2–3 mg as first-line pharmacotherapy for both sleep-onset and sleep-maintenance insomnia, positioning it ahead of sedating antidepressants or other alternatives. 1, 2

• Eszopiclone is available in New Zealand and represents a logical progression from zopiclone (the racemic mixture), as eszopiclone is the purified S-enantiomer with improved pharmacokinetic properties and a more favorable side-effect profile. 3, 4, 5

Why Quetiapine Should Have Been Avoided

• The American Academy of Sleep Medicine explicitly warns against using quetiapine for insomnia due to weak efficacy evidence and significant risks including seizures, weight gain, dysmetabolism, and neurological complications. 1

• Antipsychotics should not be used as first-line treatment for primary insomnia due to problematic metabolic side effects and lack of supporting evidence. 1

Implementation Strategy

Dosing and Administration

• Start eszopiclone 2 mg at bedtime (1 mg for adults ≥65 years or with hepatic impairment); take within 30 minutes of bedtime with at least 7–8 hours remaining before planned awakening. 1, 6

• If the 2-mg dose is well tolerated but sleep improvement is insufficient after 1–2 weeks, increase to 3 mg. 1

Mandatory Concurrent CBT-I

• Initiate or verify that CBT-I is in place before adding eszopiclone, as pharmacotherapy should supplement—not replace—behavioral interventions, which provide superior long-term outcomes with sustained benefits after medication discontinuation. 1, 2

• CBT-I includes stimulus control therapy, sleep restriction therapy, relaxation techniques, and cognitive restructuring, and can be delivered through individual therapy, group sessions, telephone-based programs, or web-based modules. 1

Alternative Second-Line Options (If Eszopiclone Fails or Is Contraindicated)

For Persistent Sleep-Maintenance Problems

• Low-dose doxepin 3–6 mg reduces wake after sleep onset by 22–23 minutes, has minimal anticholinergic effects at hypnotic doses, and carries no abuse potential. 1, 2

• Suvorexant 10 mg (orexin-receptor antagonist) reduces wake after sleep onset by 16–28 minutes via a mechanism distinct from benzodiazepine-type agents. 1

For Persistent Sleep-Onset Problems

• Zolpidem 10 mg (5 mg for older adults) shortens sleep-onset latency by approximately 15 minutes; however, the FDA warns about next-day psychomotor impairment, including impaired driving, especially if taken with less than 7–8 hours of sleep remaining. 1, 6

• Zaleplon 10 mg (5 mg for older adults) has a very short half-life, providing rapid sleep initiation with minimal next-day sedation. 1, 2

Safety Monitoring and Duration of Use

• Monitor patients after 1–2 weeks for changes in sleep-onset latency, total sleep time, nocturnal awakenings, daytime functioning, and adverse effects such as somnolence, bitter taste, headache, or memory impairment. 1

• Watch for complex sleep behaviors (e.g., sleep-driving, sleep-walking, sleep-eating); discontinue eszopiclone immediately if these occur. 1, 6

• The American College of Physicians states that evidence is insufficient to support eszopiclone use beyond 4 weeks; FDA labeling also recommends short-term use. 1

• Employ the lowest effective dose for the shortest necessary duration and taper gradually when discontinuing to avoid rebound insomnia, using CBT-I to support cessation. 1

Special Population Adjustments

• Elderly adults (≥65 years): Initiate eszopiclone at 1 mg and do not exceed 2 mg because of increased sensitivity and fall risk. 1

• Patients with hepatic impairment: Start eszopiclone at 1 mg and limit the maximum dose to 2 mg due to reduced clearance. 1

• When abuse potential is a concern (e.g., history of substance use), consider ramelteon 8 mg as a non-controlled alternative with no abuse liability. 1, 2

Common Pitfalls to Avoid

• Failing to implement CBT-I alongside medication, as behavioral interventions provide more sustained effects than medication alone. 1

• Continuing pharmacotherapy long-term without periodic reassessment, as the evidence base for extended use is limited. 1

• Using off-label antipsychotics like quetiapine for insomnia, despite clear guideline recommendations against this practice. 1