A study found low-dose mirtazapine (7.5 mg to 15 mg per day) provided a statistically significant and clinically relevant reduction of insomnia severity at 6 weeks vs. placebo but not at later time points, whereas for low-dose amitriptyline, the reduction was statistically, but not clinically relevant (1):
In this "...placebo-controlled study in 80 patients with insomnia disorder in general practice demonstrated a statistically significant and clinically relevant effect of low-dose mirtazapine (7.5–15 mg/day) on insomnia severity at 6 weeks, but not at 12 weeks during treatment or at follow-up to 12 months. Secondary sleep outcomes ....supported effectiveness of low-dose mirtazapine up to at least 6 weeks. Side effects and discontinuation due to side effects were more common in the mirtazapine group compared with placebo, suggesting lower tolerability. However, this last difference was not statistically significant.
Low-dose amitriptyline (10–20 mg/day) resulted in a statistically significant reduction in insomnia severity at week 6 only, which was smaller than clinically relevant. There were no statistically significant and clinically relevant improvements on secondary outcomes for amitriptyline during treatment or follow-up to 12 months. Amitriptyline was tolerated well..."
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