Propranolol May Fill 'Dire' Treatment Need for PTSD

Megan Brooks

January 19, 2018

New research adds to the growing body of evidence that the β-blocker propranolol (multiple brands) may help treat posttraumatic stress disorder (PTSD).

Investigators at McGill University in Montreal, Canada, found that the drug can interrupt reconsolidation of traumatic memories, making them less emotionally disturbing.

PTSD patients who actively recalled their traumatic event under the influence of propranolol showed a substantial decrease in symptom ratings compared with patients who received placebo, the investigators, led by Alain Brunet, PhD, found.

"Pre-reactivation propranolol, a treatment protocol suggested by reconsolidation theory, appears to be a novel and efficacious treatment for PTSD," they write.

The study was published online January 12 in the American Journal of Psychiatry.

A New Therapy?

The double-blind, placebo-controlled, randomized controlled trial included 60 adults with long-standing PTSD. Half were given propranolol, and half were given matching placebo 90 min before a memory reactivation session once a week for six consecutive sessions. During the initial session, 0.67 mg/kg of short-acting propranolol was given followed by 1.0 mg/kg of long-acting propranolol 2 hours later. In the five subsequent sessions, the short- and long-acting doses were given concurrently.

The decrease in PTSD symptom ratings with prereactivation propranolol was evident from both the clinician's and the participant's perspective, as indicated by significant improvement in both Clinician-Administered PTSD Scale (CAPS) and the patient-rated PTSD Checklist–Specific (PCL-S) measures.

Pretreatment CAPS scores were similar in the two groups. At the posttreatment assessment, these scores had decreased in both groups, but the decreases were significantly greater in the propranolol group, the investigators report. The intention-to-treat and per protocol pre- to posttreatment CAPS improvements, respectively, were 38% and 36% in the propranolol group vs 24% and 13% in the placebo group. The intention-to-treat and per protocol pre- to posttreatment effect sizes (Cohen's d), respectively, were 1.76 and 1.64 in the propranolol arm vs 1.25 and 0.72 in the placebo arm.

Pretreatment PCL-S scores were also similar in the two groups, and both groups experienced a decrease in PCL-S scores, but the decreases were significantly greater in the propranolol group.

The intention-to-treat and per protocol pre- to posttreatment PCL-S improvements, respectively, were 56% and 53% in the propranolol group and 15% and 10% in the placebo group. The intention-to-treat and per protocol pre- to posttreatment effect sizes, respectively, were 2.74 and 2.63 in the propranolol group and 0.55 and 0.51 in the placebo group.

The researchers note that the effect sizes and percent improvements observed with propranolol are "substantially larger" than those obtained in an earlier study in which propranolol was given once after recall of a past traumatic memory. "The use of five additional sessions appears to enhance the treatment effect of a single session," the authors note.

The effect sizes obtained with prereactivation propranolol in this study also compare well with those obtained with cognitive-behavioral therapy, the "best evidence-based treatment for PTSD," as well as those obtained with selective serotonin reuptake inhibitor therapy, "the most recommended pharmacological treatment for PTSD."

"Should these results be replicated in further studies, propranolol blockade of reconsolidation may become a new therapy for some patients with PTSD," the researchers conclude.

"Dire Need" for Effective Treatment

Commenting on the findings for Medscape Medical News, Victor Fornari, MD, director of child and adolescent psychiatry, Zucker Hillside Hospital, Glen Oaks, New York, and Cohen Children's Medical Center, New Hyde Park, New York, noted that PTSD is a "serious and prevalent behavioral health problem associated with significant morbidity and mortality, with limited evidenced-based treatments. There is an urgent and dire need for improvement in the treatment of PTSD. Currently, the best available evidence-based treatments, exposure therapy and cognitive processing therapy, produce only limited benefits.

"Further studies are needed to determine whether the addition of propranolol to this psychosocial treatment can be truly effective for the treatment of PTSD. This may become a promising treatment for PTSD," said Dr Fornari.

The study was supported by a US Army Congressionally Directed Medical Research Program grant. The authors and Dr Fornari have disclosed no relevant financial relationships.

Am J Psychiatry. Published online January 12, 2018. Abstract

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