From the Guidelines
Mirtazapine can be effective for chronic insomnia, particularly at lower doses of 7.5-15mg taken 30-60 minutes before bedtime, as it works differently than traditional sleep medications by blocking histamine H1 receptors and serotonin 5-HT2 receptors, which may reduce anxiety that interferes with sleep 1.
Key Considerations
- Mirtazapine's sedative effects are strongest at lower doses, while higher doses (30mg and above) may be less sedating due to increased noradrenergic effects.
- Common side effects include morning grogginess, increased appetite, weight gain, and dry mouth.
- Tolerance to the sedative effects may develop over time for some patients.
- Mirtazapine should be taken consistently each night, and patients should allow for 7-8 hours of sleep opportunity after taking it.
Patient Selection
- Mirtazapine may be particularly helpful for those with insomnia accompanied by depression, anxiety, or poor appetite.
- Unlike benzodiazepines or Z-drugs, mirtazapine is not habit-forming and can be appropriate for longer-term use.
- However, it should be initiated under medical supervision, especially for patients with liver disease, heart conditions, or those taking other medications.
Comparison to Other Treatments
- Cognitive behavioral therapy for insomnia (CBT-I) is an effective therapy for chronic insomnia disorder and can be performed and prescribed in the primary care setting, with evidence showing it is effective in treating the general population of adults as well as older adults with chronic insomnia disorder 1.
- While there is insufficient evidence to directly compare CBT-I and pharmacologic treatment, CBT-I is likely to have fewer harms and provides better overall value than pharmacologic treatment.
From the Research
Mirtazapine for Chronic Insomnia
- Mirtazapine is often used off-label to treat chronic insomnia, as it promotes sleep by blocking serotonin and histaminergic receptors 2.
- A randomised double-blind placebo-controlled trial (the MIRAGE study) found that mirtazapine was superior to placebo in reducing chronic insomnia symptoms in older adults, with a significant decrease in Insomnia Severity Index (ISI) score after 28 days of treatment 2.
- Another study compared the efficacy of trazodone and mirtazapine in patients with chronic insomnia, and found that both medications were effective in reducing insomnia symptoms, with no significant difference between the two groups 3.
- The DREAMING study is a randomised, double-blind, placebo-controlled trial that aims to assess the effectiveness of low-dose amitriptyline and mirtazapine for insomnia disorder in general practice, with results pending 4.
- Mirtazapine is not approved by the U.S. Food and Drug Administration for the treatment of insomnia, but it is often prescribed off-label due to its sedating effects 5, 6.
Efficacy and Safety
- The MIRAGE study found that mirtazapine was well-tolerated, with no severe adverse events reported, but 6 participants in the mirtazapine group discontinued treatment due to adverse events 2.
- The study comparing trazodone and mirtazapine found that both medications were effective at low doses, with a higher percentage of responders in patients with lower final dosage 3.
- The safety and efficacy of long-term use of mirtazapine for insomnia is not well-established, and the decision to treat chronic insomnia disorder with long-term hypnotics should be individualized 6.
Comparison to Other Treatments
- Cognitive behavioral therapy for insomnia (CBT-I) is considered the primary treatment modality for insomnia, but pharmacotherapy is often used due to difficulties with access and higher cost 6.
- Mirtazapine is one of several medications that can be used to treat insomnia, including benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonists, and selective melatonin receptor agonists 5, 6.