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International Journal of Neuropsychopharmacology logoLink to International Journal of Neuropsychopharmacology
. 2025 Aug 18;28(Suppl 2):ii11–ii12. doi: 10.1093/ijnp/pyaf052.021

208. TRIHEXYPHENIDYL REDUCES FLASHBACKS IN PATIENTS WITH POSTTRAUMATIC STRESS DISORDER (PTSD)

S Katsumasa 1
PMCID: PMC12359652

Abstract

Background

Post-Traumatic Stress Disorder (PTSD) is a complex mental health condition triggered by experiencing or witnessing traumatic events. Despite extensive research, the precise mechanisms underlying PTSD remain unclear. Recent data from patients have shown that central cholinergic agents targeting the basal forebrain nucleus AcH4 and the amygdala, which are involved in memory-related circuits, have demonstrated dramatic effects in alleviating PTSD symptoms.

Aims & Objectives

This study aims to develop a new therapy for reducing flashbacks in the posttraumatic stress disorder (PTSD).

Method

Previous studies have proved the potentiality of anticholinergic in reducing flashbacks in PTSD. This report describes the effects of the central anticholinergic drug trihexyphenidyl, which penetrates the blood–brain barrier (BBB) among 7 patients suffering from PTSD flashbacks.

Results

Drug effects were assessed using psychological tests, including a self-evaluation score, the IES-R (Impact of Events Scale-Revised), and CAPS (Clinician-administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders-IV [DSMIV]).The mean of the self-evaluation score improved from 100 to 17.14 after the treatment, and the mean IES-R score improved to 25.57 from 70.42. The CAPS mean frequency (F) and intensity (I) of B-1(unwanted memories) improved from 3.42 to0.71and 3.42 to 0.57, respectively, after treatment. The mean F and I of B-2 (unpleasant dreams) improved from 1.85 to 0.42and 2.00 to 0.28, respectively. The mean of F and I of B-3 (flashbacks, etc.) improved from 3.71 to 0.85 and 3.28 to 0.85, respectively. Complete remission was achieved in 3 of 7 cases (48%), and partial remission was achieved for the remaining 4 (52%). Therefore, at least some remission was achieved in all patients in this study.

Discussion & Conclusions

The central anticholinergic drug trihexyphenidyl is a novel and successful medical therapy in reducing flashbacks in subjects suffering from PTSD. This result suggests that the origin of flashbacks in PTSD is closely related to abnormal excitement of memory-related circuits comprised of the acetylcholine-based basal forebrain, amygdala, and hippocampus.


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