Augmentation with prazosin for patients with depression and a history of trauma: A randomised, double‐blind, placebo‐controlled study.

Guo, Ping; Xu, Yong; Lv, Liang; Feng, Min; Fang, Yu; Cheng, Shanfei; Xiao, Xiaoqing; Huang, Juanjuan; Sheng, Wei; Wang, Shikai; Chen, Huanxin

Introduction: Depression with a history of trauma often responds poorly to conventional antidepressants and has a poor prognosis. Prazosin, an α1‐adrenoceptor blocker, has shown promise in treating post‐traumatic stress disorder symptoms, particularly nightmares. Its potential in treating depression with trauma history warrants investigation. Aims of the Study: This randomised, double‐blind, placebo‐controlled study aimed to investigate the efficacy and tolerability of low‐dose prazosin (0.5–1 mg/day) as an augmentation strategy in patients with depression and a history of trauma. We sought to determine if prazosin could provide rapid symptom improvement and enhance overall treatment response compared to placebo in this difficult‐to‐treat patient population. Methods: This randomised, double‐blind, placebo‐controlled clinical study included 59 patients with first‐episode or recurrent unipolar or bipolar depression. After basic antidepressant treatment, they were randomly assigned to a prazosin (0.5–1 mg/day) or placebo group for a 6‐week double‐blind controlled study. The Montgomery–Åsberg Depression Rating Scale, 17‐item Hamilton Depression Scale (HAMD‐17), and Hamilton Anxiety Scale (HAMA) were used to evaluate efficacy. Results: There were no significant differences in the results of the demographic and clinical symptom assessment between the two groups (p > 0.05). The difference between the HAMD‐17 and HAMA scores was statistically significant after 3 days of treatment (p < 0.05). The difference in response rate between the two groups was statistically significant after week 4 of treatment (end of week 4, 56.7% vs. 24.1%, p = 0.011; end of week 6, 80.0% vs. 48.3%, p = 0.011). The incidence of adverse reactions in the prazosin and placebo groups was 20.0% and 24.1%, respectively, with no statistically significant differences (p > 0.05); however, the prazosin group had a lower incidence of sleeplessness or nightmares (3.3% vs. 20.7%, p = 0.039) but a higher incidence of orthostatic hypotension (16.7% vs. 0%, p = 0.007). The severity of orthostatic hypotension was mild to moderate. Conclusion: Low‐dose prazosin can effectively improve the emotional symptoms of patients with depression and a history of trauma, and the common adverse reaction is mild‐to‐moderate orthostatic hypotension. Clinical Trial Registration: ChiCTR2200063642.

ORTHOSTATIC hypotension; BIPOLAR disorder; EMOTIONAL trauma; MENTAL depression; PSYCHOTHERAPY

Acta Psychiatrica Scandinavica, 2025, Vol 151, Issue 2, p142

0001-690X

Academic Journal

10.1111/acps.13763