Mirtazapine for Methamphetamine Withdrawal-Associated Insomnia
No published article supports the use of low-dose mirtazapine (15-30 mg at bedtime) specifically for treating insomnia associated with methamphetamine withdrawal. In fact, the only randomized controlled trial directly examining this question found that mirtazapine did not improve retention or alleviate methamphetamine withdrawal symptoms, including insomnia 1.
Evidence Against This Specific Use
The 2008 placebo-controlled trial by McGregor et al. 1 specifically tested mirtazapine (15 mg for 2 days, then 30 mg for 12 days) for methamphetamine withdrawal in an outpatient setting. The study found no significant differences between mirtazapine and placebo groups in retention or any symptom measures, including insomnia as measured by the Athens Insomnia Scale. The authors concluded that mirtazapine does not facilitate retention or recruitment in outpatient methamphetamine withdrawal treatment.
Recent Evidence for Methamphetamine Use Disorder
More recent evidence suggests a different role for mirtazapine. A 2026 phase 3 randomized controlled trial 2 demonstrated that mirtazapine 30 mg daily reduced days of methamphetamine use (mean reduction of 7.0 days vs 4.8 days with placebo over 28 days). However, this study found no significant effects on secondary endpoints including insomnia, despite insomnia being measured as an outcome.
General Insomnia Guidelines
For general chronic insomnia (not specific to methamphetamine withdrawal), clinical practice guidelines mention mirtazapine only as a third-line option:
- The 2008 American Academy of Sleep Medicine guideline 3 lists mirtazapine among sedating low-dose antidepressants that "may be considered" when accompanied with comorbid depression or after other treatment failures, but notes that "evidence for their efficacy when used alone is relatively weak"
- The guideline specifically states these medications are not FDA approved for insomnia and their efficacy is not well established 3
- The 2014 cancer-related insomnia guideline 4 specifically notes that the Alberta Medical Association did not recommend prescribing mirtazapine due to relative lack of evidence or side effects
Important Caveats
Mirtazapine is associated with significant side effects relevant to this population:
- Weight gain (noted in all guidelines 3, 5)
- Drowsiness/somnolence (47% in recent trial 2)
- 23% discontinuation rate due to adverse events in the methamphetamine use disorder trial 2
Bottom Line
There is no published article supporting the specific claim that low-dose mirtazapine (15-30 mg at bedtime) effectively treats insomnia associated with methamphetamine withdrawal. The only direct evidence 1 shows no benefit for this indication. While mirtazapine may reduce methamphetamine use itself 2, it does not appear to specifically address withdrawal-related insomnia.