The evidence for antipsychotics in post-traumatic stress disorder (PTSD) is limited and inconsistent, largely based on small, short-duration studies. Risperidone is the most studied agent, showing modest symptom improvement versus placebo in some trials, mainly as adjunctive therapy, but with inconsistent findings and no clear benefit in selective serotonin reuptake inhibitors (SSRI)-resistant PTSD. Olanzapine has mixed results, with some trials reporting symptom or sleep improvements and oth...
The 2023 Veterans Affairs Department of Defense (VA/DoD) guidelines on management of post-traumatic stress disorder (PTSD) suggests against the use of any antipsychotic, including aripiprazole, asenapine, brexpiprazole, cariprazine, iloperidone, lumateperone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, or ziprasidone, for augmentation of medications for PTSD, citing very low-quality evidence, small sample sizes, inconsistent efficacy, and a risk-benefit profile in which well-established harms outweigh uncertain benefits. Evidence reviewed showed that risperidone, aripiprazole, and olanzapine were the only agents studied as augmentation, and none demonstrated consistent or statistically significant improvement in overall PTSD outcomes compared with placebo. The 2018 National Institute for Health and Care Excellence (NICE) similarly states that antipsychotics are not first-line treatments for PTSD and should not be considered alternatives to trauma-focused psycholog...
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A search of the published medical literature revealed
2 studies investigating the researchable question:
Which antipsychotics have evidence in PTSD?
Level of evidence
C - Multiple studies with limitations or conflicting results
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[1] Veterans Affairs Department of Defense (VA/DoD). Clinical Practice Guideline for Management of Posttraumatic Stress Disorder and Acute Stress Disorder. Published 2023. Accessed January 15, 2026. https://www.healthquality.va.gov/HEALTHQUALITY/guidelines/MH/ptsd/VA-DoD-CPG-PTSD-Full-CPG-Edited-111624-V5-81825.pdf
[2] National Institute for Health and Care Excellence (NICE). Post-traumatic stress disorder. Published December 2018. Accessed January 15, 2026.
[3] Berger W, Mendlowicz MV, Marques-Portella C, et al. Pharmacologic alternatives to antidepressants in posttraumatic stress disord...