Does reducing Remeron (Mirtazapine) 15mg to 7.5mg at bedtime (QHS) or administering every other day cause less sedation during gradual dose reduction (GDR)?

From the Guidelines

Reducing Remeron (Mirtazapine) 15mg to 7.5mg daily at bedtime is generally better than administering every other day for a gradual dose reduction (GDR), as it provides more consistent blood levels and typically results in fewer withdrawal symptoms and less rebound sedation. When considering the management of sedation during GDR, it's essential to prioritize the patient's quality of life and minimize potential morbidity. The approach of reducing the dose to 7.5mg daily at bedtime offers a more stable pharmacological effect, which is crucial for maintaining patient comfort and reducing the risk of adverse effects. The unique pharmacology of mirtazapine, where antihistamine effects are more pronounced at lower doses, should be considered in the dose reduction strategy 1. Key points to consider in the GDR of Remeron (Mirtazapine) include:

• Monitoring patients for withdrawal symptoms like insomnia, anxiety, or dizziness
• Maintaining the reduced dose for at least 2-4 weeks before considering further reductions
• Potential subsequent reductions to 3.75mg daily before complete discontinuation, based on patient tolerance It's also important to note that certain antidepressants, including mirtazapine, are used off-label for the treatment of insomnia, and their efficacy for this indication is not well established 1. However, in the context of GDR, the focus should be on minimizing sedation and withdrawal symptoms while prioritizing the patient's quality of life and safety. Given the available evidence, the most recent and relevant study 1 supports the approach of reducing the dose to 7.5mg daily at bedtime for a more stable and consistent effect.

From the Research

Reducing Remeron (Mirtazapine) Dosage

• Reducing the dosage of Remeron (Mirtazapine) from 15mg to 7.5mg at bedtime (QHS) or administering every other day may help minimize sedation during gradual dose reduction (GDR) 2, 3.
• Mirtazapine is known to cause sedation, with 19% of patients experiencing excessive sedation in placebo-controlled trials 2.
• The drug's sedative effects are likely due to its antihistamine properties and its ability to block certain adrenergic and serotonin receptors 4.
• Reducing the dosage or frequency of administration may help mitigate these sedative effects, although the optimal dosage reduction strategy has not been specifically studied 5, 6.

Pharmacokinetics and Dosage

• Mirtazapine is extensively metabolized in the liver, with a mean elimination half-life of approximately 22 hours, making it suitable for once-daily administration 2, 3.
• The recommended starting dosage of mirtazapine is 15 mg/day, which can be increased to 30 mg/day or more as needed 2, 3.
• However, the effects of reducing the dosage or frequency of administration on the drug's efficacy and safety have not been extensively studied 5, 6.

Clinical Efficacy and Safety

• Mirtazapine has been shown to be effective in the treatment of major depression, with efficacy comparable to other antidepressants 2, 5, 6, 3.
• The drug is generally well-tolerated, with common adverse effects including dry mouth, sedation, increased appetite, and weight gain 2, 5, 6, 3.
• However, the safety and efficacy of reducing the dosage or frequency of administration have not been extensively studied, and patients should be closely monitored for any changes in their condition 5, 6.