What is the efficacy of Mirtazapine (Remeron) for insomnia?

From the Guidelines

Mirtazapine can be considered for sleep problems at lower doses, typically 7.5-15 mg taken 30-60 minutes before bedtime, as it works primarily on histamine receptors, producing a sedative effect that helps with sleep onset and maintenance. The medication is available as regular tablets or orally disintegrating tablets, with effects typically beginning within an hour of taking it. Paradoxically, higher doses (30-45 mg) may be less sedating because at these levels, the medication activates noradrenergic pathways that can be stimulating. Common side effects include morning grogginess, increased appetite, weight gain, and dry mouth. Patients should be aware that mirtazapine may take several days to reach its full effect for sleep, and it should not be abruptly discontinued after regular use. While primarily prescribed as an antidepressant, mirtazapine's off-label use for insomnia is common, especially in patients who have not responded to other sleep medications or who might benefit from its additional effects on mood and anxiety 1.

Some key points to consider when prescribing mirtazapine for sleep include:

• The choice of a specific pharmacological agent should be directed by symptom pattern, treatment goals, past treatment responses, patient preference, cost, availability of other treatments, comorbid conditions, contraindications, concurrent medication interactions, and side effects 1.
• Sedating antidepressants, such as mirtazapine, may be considered when accompanied by comorbid depression or in the case of other treatment failures 1.
• The efficacy of low-dose sedating antidepressants, including mirtazapine, for insomnia is relatively weak, and no specific agent within this group is recommended as preferable to the others in this group 1.
• The 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guidelines advise against the use of benzodiazepines or trazodone for the treatment of chronic insomnia disorder, and recommend cognitive-behavioral therapy for insomnia (CBT-I) as the initial treatment intervention 1.

Overall, while mirtazapine may be effective for sleep problems, its use should be carefully considered and monitored, taking into account the potential benefits and risks, as well as the availability of other treatment options.

From the Research

Mirtazapine for Sleep

• Mirtazapine is an antidepressant that has been used off-label for the treatment of insomnia, particularly in patients with comorbid depression or anxiety disorders 2, 3.
• The exact mechanism of mirtazapine's sleep-promoting effects is not fully understood, but it is thought to be related to its ability to increase noradrenergic and serotonergic neurotransmission, as well as its blockade of central α2-adrenergic auto- and heteroreceptors 4.
• Studies have shown that mirtazapine can improve sleep quality and reduce symptoms of insomnia in patients with major depression, including increasing total sleep time, sleep efficiency, and slow-wave sleep percentages, and decreasing sleep latency and stage awake percentage 5.
• Mirtazapine has also been compared to other antidepressants, such as amitriptyline and trazodone, and has been found to have a similar or superior efficacy in improving sleep quality, with a more favorable tolerability profile 4.
• A randomized, double-blind, placebo-controlled trial is currently underway to assess the effectiveness of low-dose mirtazapine for insomnia disorder in general practice, with results expected to provide further insight into the use of mirtazapine for sleep disorders 3.

Dosage and Administration

• The recommended starting dosage of mirtazapine for sleep disorders is typically lower than that used for depression, ranging from 7.5-15 mg/day 3.
• Mirtazapine can be administered once daily, and its bioavailability is approximately 50%, with peak plasma concentrations reached within 2-3 hours after oral administration 4.

Safety and Tolerability

• Mirtazapine is generally well-tolerated, with common side effects including drowsiness, dry mouth, and increased appetite 4.
• Mirtazapine has a low potential for inducing seizures and is considered safe in overdose, with excessive somnolence being the only reported symptom in cases of overdose 4.
• However, mirtazapine can cause changes in laboratory parameters, including granulocytopenia and elevated alanine aminotransferase levels, and should be used with caution in patients with hepatic or renal insufficiency 4.