Can I use Mirtazapine with Zopiclone (Eszopiclone) for depression and insomnia?

Using Mirtazapine with Zopiclone for Depression and Insomnia

The combination of mirtazapine and zopiclone can be used for depression and insomnia, but should be prescribed with caution due to potential additive sedative effects that may increase risk of falls and cognitive impairment, especially in elderly patients. While both medications can be effective for their respective indications, their combined use requires careful monitoring.

Medication Profiles and Rationale

Mirtazapine for Depression with Insomnia

• Mirtazapine is an atypical antidepressant that has been shown to be safe in patients with cardiovascular disease 1
• It offers additional benefits beyond depression treatment:
  • Promotes sleep through its sedating properties
  • Stimulates appetite, which may be beneficial in depressed patients with poor intake
  • Improves objective sleep parameters (sleep latency, sleep efficiency, and wake after sleep onset) within 2 weeks of treatment 2

Zopiclone for Insomnia

• Zopiclone (and eszopiclone) belongs to the non-benzodiazepine hypnotic class
• Current guidelines recommend short-intermediate acting benzodiazepine receptor agonists like zopiclone as first-line pharmacological treatment for insomnia 1
• It has shown efficacy comparable to benzodiazepines with potentially fewer residual effects 3

Treatment Algorithm for Depression with Insomnia

1. Initial Approach:

   • Consider cognitive behavioral therapy for insomnia (CBT-I) as first-line treatment before or alongside pharmacotherapy 1
   • For patients with both depression and insomnia, a sedating antidepressant like mirtazapine may be sufficient as monotherapy

2. When to Consider Combination Therapy:

   • If mirtazapine alone is insufficient for managing insomnia symptoms
   • For short-term use during the initial weeks while waiting for the full antidepressant effect of mirtazapine

3. Monitoring Requirements:

   • Assess for excessive daytime sedation, cognitive impairment, and fall risk
   • Follow patients regularly (every few weeks initially) to evaluate effectiveness and side effects 1
   • Use the lowest effective dose of both medications

Important Precautions and Considerations

• Risk of Additive Sedation: Both medications have sedating properties that may compound each other
• Elderly Patients: Use lower doses and monitor more closely for adverse effects
• Duration of Zopiclone Use:
  • Limit to short-term use (≤4 weeks) whenever possible
  • Long-term hypnotic use should be accompanied by consistent follow-up and monitoring 1
• Discontinuation Strategy:
  • Plan for gradual tapering of zopiclone once depression and sleep improve
  • Studies show that discontinuation of hypnotics after combined therapy with antidepressants does not typically result in rebound insomnia or worsening depression 4

Evidence for Combined Therapy

Research on eszopiclone (zopiclone's isomer) combined with SSRIs has shown:

• Improved sleep outcomes
• Enhanced depression response rates
• No significant rebound insomnia after discontinuation of the hypnotic 5, 4

While these studies used SSRIs rather than mirtazapine, they support the concept of short-term hypnotic use alongside antidepressant therapy.

Alternatives to Consider

If the combination raises concerns:

• For insomnia: Consider ramelteon (melatonin receptor agonist) which has fewer cognitive and psychomotor effects 1
• For depression with insomnia: Consider trazodone as an alternative sedating antidepressant 1

Remember that hypnotics should be used at the lowest effective dose and for the shortest duration necessary, with the goal of transitioning to non-pharmacological sleep strategies and antidepressant monotherapy when possible.