Frequently Asked Questions

In this retrospective VA outpatient cohort, mirtazapine 3.75 mg was associated with clinically relevant short-term improvement in insomnia severity over 1 to 3 months. Among all 53 veterans evaluated, 47% had a clinically significant reduction in Insomnia Severity Index (ISI) score of more than 7 points, and 32% achieved recovery, defined as an ISI score of 7 or lower. In patients who completed treatment and had a valid follow-up ISI score, the mean ISI decreased from 20.4 (4.58) at baseline to 8.9 (6.76) at 1 to 3 months, with a mean change of 11.3 (6.46).

Among veterans who completed treatment, the mean ISI score improved from 20.4 (4.58) at baseline to 8.9 (6.76) at 1 to 3 months. The mean change in ISI score was 11.3 (6.46). The authors also reported that all treatment completers had either a constant or decreased ISI score at follow-up.

In the full sample of 53 veterans, 47% had a clinically significant response, defined as an ISI decrease of more than 7 points, and 32% achieved recovery, defined as an ISI score of 7 or lower. These proportions were calculated across all veterans evaluated in the study.

The study included 53 veterans aged 31 to 81 years in an outpatient psychiatric practice, including 49 men and 4 women. They were prescribed ultra-low-dose mirtazapine because traditional sleep aids had not been effective.

This was a retrospective chart review conducted in a Veterans Affairs outpatient setting. The investigators evaluated veterans prescribed mirtazapine 3.75 mg between September 5, 2024, and March 7, 2025, and measured insomnia severity using the validated Insomnia Severity Index at baseline and again 1 to 3 months after treatment initiation.

This study evaluated short-term outcomes over 1 to 3 months after starting mirtazapine 3.75 mg. The authors specifically stated that their data do not support long-term effectiveness and instead provide a foundation for future studies.

The authors conclude that clinicians should consider low-dose mirtazapine for treatment-resistant insomnia in patients with persistent symptoms despite adequate medication trials. In the discussion, they also note that low-dose mirtazapine can be considered in individuals who do not experience efficacy from other insomnia medications such as trazodone, amitriptyline, or doxepin.

The article states that low-dose mirtazapine may be an alternative when cognitive-behavioral therapy for insomnia is not recommended or is contraindicated. The authors note that CBT-I can be difficult to use in some patients because of its sleep-restriction component, including those with epilepsy, bipolar disorders, high fall risk, untreated disorders of excessive sleepiness, or parasomnias.

The article states that mirtazapine is a strong H1 receptor antagonist, which provides sedative and hypnotic effects. The authors also cite prior literature showing that low doses can affect sleep duration and sleep architecture by reducing wakefulness after sleep onset and increasing total sleep time.

The main limitations are that this was a retrospective, small-sample study of veterans, most of whom were male, and it had no control group. In addition, 17 of the 53 veterans evaluated did not complete treatment. Because of these limitations, the findings have limited generalizability and do not establish comparative efficacy or long-term benefit.