Mirtazapine for insomnia

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):

• low doses of the antidepressants amitriptyline and mirtazapine are widely prescribed as an alternative treatment when there is a need for sleep medication that can be used for several months
  • intervention consisted of a 16-week daily intake of either one or two tablets of mirtazapine 7.5 mg, amitriptyline 10 mg, or placebo
  • patients were instructed to start with one tablet per night, taken 2 hours to 30 minutes before bedtime
• demonstrates a statistically significant and clinically relevant effect of low-dose mirtazapine (7.5-15mg/day) on insomnia severity at 6 weeks, but not at 12 weeks during treatment nor at follow-up up to 12 months

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..."

Reference:

1. Bakker M et al. Effectiveness of low-dose amitriptyline and mirtazapine in patients with insomnia disorder with sleep maintenance problems: a randomised, double-blind, placebo-controlled trial in general practice (DREAMING). BJGP.2024.0173.