Clinical Potential of Mirtazapine in Anxiety and Trauma-Related Disorders: A Systematic Review and Meta-Analysis of Current Evidence.

OBJECTIVE

Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) with sedative features that may be advantageous for anxiety and trauma-related disorders, yet its role remains unclear.

METHODS

We systematically reviewed and meta-analyzed the evidence on mirtazapine in anxiety disorders, major depressive disorder evaluating anxious symptoms, and trauma-related disorders, following PRISMA guidelines. Following a pre-registered protocol (https://osf.io/562zj/?view_only=0f596df97bc74b2bb25ebbf1dcbd7589), we searched PubMed/EMBASE/CENTRAL/ClinicalTrials.gov/WHO-ICTRP from inception until 07/07/2025. The co-primary outcomes were efficacy (symptom decrease-Standardized Mean Difference/SMD and response-Risk Ratio/RR) and acceptability.

RESULTS

Out of 799 identified records, 37 studies were included. In generalized anxiety disorder (GAD), mirtazapine paralleled selective serotonin reuptake inhibitors (SSRIs) (SMD = -0.14, 95% C.I. [-0.38, 0.09], p = 0.23, I2 = 13.3%, τ2 = 0.01, k = 5, n = 330), benzodiazepines (SMD = -0.03, 95% C.I. [-0.83, 0.77], p = 0.94, I2 = 85.9%, τ2 = 0.43, k = 4, n = 233). In major depressive disorder (MDD), mirtazapine slightly outperformed SSRIs regarding anxiety (SMD = -0.16, 95% C.I. [-0.25, 0.07], p < 0.01, I2 = 0%, τ2 = 0, k = 10, n = 1732), and paralleled tricyclic antidepressants (TCAs). In post-traumatic stress disorder, SSRI augmentation was effective. Acceptability was comparable to placebo and SSRIs.

DISCUSSION: Mirtazapine was more effective than SSRIs for anxiety in MDD and may be preferred when anxiety is relevant. In GAD, mirtazapine may serve as an alternative to first-line agents, and further regulatory explorations are warranted. In PTSD, mirtazapine has potential as an augmentation strategy. Mirtazapine was generally well tolerated and may be advantageous for patients requiring rapid effect or relief from sleep disturbances.