Summary: Trihexyphenidyl, a centrally acting anticholinergic medication commonly used in parkinsonism, may reduce distressing memory flashbacks and nightmares in people with post-traumatic stress disorder (PTSD).
Source: Cactus Communications
Correction: A previous version stated that trihexyphenidyl had no adverse effects. That statement was removed because some adverse effects have been reported in the scientific literature.
Post-traumatic stress disorder (PTSD) affects many people after exposure to traumatic or life-threatening events. Nightmares and intrusive flashbacks are among the most debilitating symptoms, and current treatments do not reliably relieve these symptoms for everyone.
Researchers continue to explore the brain mechanisms that underlie PTSD and to test medications that might improve symptoms. The exact neurological pathways of PTSD remain incompletely understood, which has made the search for effective treatments challenging.
A team of Japanese clinicians from the Sogo PTSD Institute, Medical Corporation Sogokai, led by Dr. Masanobu Sogo, report promising clinical observations pointing to a possible treatment: the centrally acting anticholinergic drug trihexyphenidyl. Their findings were published in the journal Brain and Behavior and describe a rapid reduction in PTSD-related nightmares and flashbacks in many patients treated with this medication.
Trihexyphenidyl is an anticholinergic agent that blocks acetylcholine activity in the central nervous system and is commonly prescribed to manage parkinsonism and to counteract certain central side effects of other medications. The drug has been in clinical use for decades.
The investigators’ interest in anticholinergics for PTSD began with an unexpected clinical observation in 2009. A patient with severe, long-standing PTSD—experiencing persistent flashbacks and nightmares for nine years—was hospitalized elsewhere for bacterial diarrhea and received an intravenous infusion that included scopolamine butyl bromide (SB), a peripheral anticholinergic that normally does not cross the blood‑brain barrier. Within twenty minutes of the infusion the patient’s flashbacks disappeared.
Because scopolamine butyl bromide is generally considered unable to penetrate the brain, the team hypothesized that in severe PTSD the blood‑brain barrier or local brain activity might be altered, allowing peripheral anticholinergic agents to access central cholinergic circuits. They focused on the basal forebrain cholinergic system—particularly the nucleus basalis of Meynert—which is a major source of acetylcholine and is implicated in memory and attention processes. The researchers proposed that excessive acetylcholine activity within memory‑related circuits centered on the Meynert nucleus could contribute to intrusive memories, and that centrally acting anticholinergic drugs could suppress that abnormal activity and reduce flashbacks and nightmares.
To explore this idea, Dr. Sogo and colleagues conducted an exploratory clinical study of trihexyphenidyl in patients with refractory PTSD symptoms. They treated 34 patients who had experienced PTSD-related nightmares and flashbacks despite several years of psychiatric care. The trial included an open-label arm (n = 22) and a single‑blind arm (n = 12). Outcomes were assessed using standard measures, including the Clinician-Administered PTSD Scale (CAPS) and the Impact of Event Scale–Revised (IES‑R).
The results were notable: 88% of participants showed improvement to mild or no nightmares on CAPS, and 79% showed similar improvement for flashbacks. The authors also reported a rapid onset of effect in many patients, with some noting benefits within one to two days after starting trihexyphenidyl. These findings suggest that centrally acting anticholinergic treatment may reduce two of the most intrusive symptoms of PTSD—nightmares and flashbacks—in patients who do not respond to conventional psychiatric therapies.
Dr. Sogo commented that, to their knowledge, this study is the first pharmacological report describing trihexyphenidyl’s use for PTSD-related nightmares that have been refractory to standard treatment. While the clinical signals are encouraging, the authors emphasize that larger, double‑blind randomized controlled trials are necessary to confirm efficacy, clarify optimal dosing, evaluate safety, and understand possible side effects in this population.
Repurposing an established, inexpensive medication such as trihexyphenidyl could be a valuable avenue if further research confirms these early results. At the same time, clinicians and patients should weigh potential benefits against known anticholinergic risks and reported adverse events. Continued investigation into the role of central cholinergic circuits in PTSD may also advance our understanding of the disorder and lead to new therapeutic strategies.
About this PTSD research news
Source: Cactus Communications
Contact: Indrani Das – Cactus Communications
Image: The image is in the public domain
Original Research: Open access. “Centrally acting anticholinergic drug trihexyphenidyl is highly effective in reducing nightmares associated with post‑traumatic stress disorder” by Masanobu Sogo et al., published in Brain and Behavior.
Abstract
Centrally acting anticholinergic drug trihexyphenidyl is highly effective in reducing nightmares associated with post-traumatic stress disorder
Introduction
Following the clinical observation with scopolamine butyl bromide, the investigators examined whether a centrally acting anticholinergic medication could reduce PTSD‑related flashbacks and nightmares.
Methods
Trihexyphenidyl (TP) was administered to 34 patients with treatment‑resistant PTSD-related nightmares and flashbacks (open‑label, n = 22; single‑blind, n = 12). These patients had previously undergone psychiatric treatment for approximately two to fifteen years without satisfactory improvement. Effects were measured using the Clinician‑Administered PTSD Scale (CAPS) and the Impact of Event Scale–Revised (IES‑R).
Results
Most patients experienced marked improvement: 88% improved to none or mild nightmares on CAPS, and 79% improved for flashbacks.
Conclusion
This exploratory study is the first to report potential efficacy of trihexyphenidyl for refractory PTSD‑related nightmares and flashbacks. The authors call for further double‑blind, randomized controlled trials to verify these findings, determine safety and dosing considerations, and better understand the underlying mechanism.