Is it appropriate to prescribe zopiclone 7.5 mg nightly for one week to a patient already taking melatonin 2 mg nightly for insomnia?

Adding Zopiclone to Melatonin for Insomnia

No—prescribing zopiclone 7.5 mg for one week to a patient already taking melatonin 2 mg is not advisable because melatonin lacks efficacy for chronic insomnia and should be discontinued, while zopiclone can be initiated as monotherapy only after implementing Cognitive Behavioral Therapy for Insomnia (CBT-I) first. 1, 2

Why Melatonin Should Be Stopped

• The American Academy of Sleep Medicine explicitly recommends against using melatonin 2 mg for sleep-onset or sleep-maintenance insomnia in adults, citing very low quality evidence showing no clinically meaningful reduction in sleep latency, total sleep time, or sleep quality. 1, 2
• Meta-analysis of high-quality trials in adults >55 years found melatonin produced no significant improvement in sleep latency (mean difference +17.9 minutes; 95% CI -3.8 to +39.5), sleep efficiency, or subjective sleep quality compared to placebo. 2
• The current regimen of melatonin 2 mg is ineffective and should be discontinued before starting evidence-based pharmacotherapy. 1, 2

Mandatory First Step: Cognitive Behavioral Therapy for Insomnia (CBT-I)

• The American Academy of Sleep Medicine and American College of Physicians issue a strong recommendation that all adults with chronic insomnia receive CBT-I as the initial treatment before any pharmacotherapy, because it demonstrates superior long-term efficacy with sustained benefits after medication discontinuation. 1, 2, 3
• CBT-I includes stimulus control therapy (use bed only for sleep, leave bed if unable to sleep within 20 minutes), sleep restriction therapy (limit time in bed to actual sleep time plus 30 minutes), relaxation techniques, and cognitive restructuring of negative sleep beliefs. 2, 3
• CBT-I can be delivered via individual sessions, group programs, telephone, web-based platforms, or self-help books, making it feasible even with limited resources. 2

When Zopiclone May Be Appropriate

• Zopiclone 7.5 mg is a guideline-recommended first-line benzodiazepine receptor agonist for both sleep-onset and sleep-maintenance insomnia, but only after CBT-I has been initiated or attempted. 1, 2, 3
• The American Academy of Sleep Medicine positions zopiclone alongside eszopiclone, zolpidem, and zaleplon as appropriate pharmacotherapy when behavioral interventions are insufficient. 1, 2
• Zopiclone demonstrates efficacy equivalent to or greater than benzodiazepines (flurazepam, nitrazepam, temazepam, triazolam) with a relatively low propensity for residual daytime effects. 4, 5

Critical Safety Concerns with Zopiclone 7.5 mg

• Zopiclone 7.5 mg causes moderate to severe driving impairment the next morning (10-11 hours post-dose), comparable to blood alcohol concentration of 0.5-0.8 mg/mL, which is associated with a 2- to 3-fold increase in traffic accident risk. 6
• This impairment does not differ by sex or age (tested up to 75 years), and patients must be warned to avoid driving or skilled work the morning after intake. 6
• All benzodiazepine receptor agonists carry FDA warnings for complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating) requiring immediate discontinuation if observed. 2, 7
• Bitter taste occurs in approximately 3.6% of patients but is usually mild and does not require discontinuation. 4, 5

Duration and Monitoring Limitations

• FDA labeling and European guidelines indicate zopiclone is intended for short-term use (≤4 weeks) for acute insomnia; evidence beyond 4 weeks is insufficient to support routine long-term use. 2, 7, 8
• Prescribing zopiclone for only one week is appropriate for acute insomnia but does not address the underlying chronic sleep problem requiring CBT-I. 1, 2, 3
• Reassessment after 1-2 weeks is mandatory to evaluate efficacy on sleep latency, total sleep time, nocturnal awakenings, and daytime functioning, and to monitor for adverse effects including morning sedation and complex sleep behaviors. 2, 7

Recommended Treatment Algorithm

1. Discontinue melatonin 2 mg immediately because it lacks efficacy for chronic insomnia. 1, 2

2. Initiate CBT-I immediately with stimulus control, sleep restriction, relaxation techniques, and cognitive restructuring; this can be delivered via multiple formats. 1, 2, 3

3. If CBT-I alone is insufficient after 4-8 weeks, add zopiclone 7.5 mg at bedtime (ensuring ≥7-8 hours remain before awakening) as supplemental therapy, not replacement for behavioral interventions. 2, 3, 7

4. Reassess after 1-2 weeks to evaluate sleep parameters and adverse effects; if ineffective, switch to an alternative first-line agent (eszopiclone 2-3 mg, zolpidem 10 mg, or zaleplon 10 mg for sleep-onset; low-dose doxepin 3-6 mg for sleep-maintenance). 1, 2, 3

5. Limit zopiclone use to ≤4 weeks and taper gradually when discontinuing to avoid rebound insomnia, using CBT-I to facilitate successful cessation. 2, 8

Common Pitfalls to Avoid

• Starting zopiclone without first implementing CBT-I leads to less durable benefit and missed opportunity for long-term sleep improvement. 1, 2
• Continuing ineffective melatonin delays appropriate evidence-based treatment. 1, 2
• Failing to warn patients about next-morning driving impairment with zopiclone 7.5 mg creates serious safety risks. 6
• Prescribing zopiclone for only one week without addressing the chronic nature of insomnia through CBT-I perpetuates the sleep problem. 1, 2, 3
• Using zopiclone beyond 4 weeks without periodic reassessment and tapering plan is not supported by evidence. 2, 7, 8