Propranolol Shows Potential as Pharmacokinetic Treatment for Adjustment Disorder

Adjustment disorder symptoms significantly decreased with propranolol treatment and symptom improvement maintained at 4-months’ follow-up on all outcomes.

Propranolol therapy is associated with reduced symptoms of adjustment disorder (AD) and likely should be evaluated for safety and efficacy in larger clinical trials, according to findings published in Journal of Affective Disorders.

Researchers conducted a single-blind study at the Research Center of the Douglas Mental Health University Institute in Canada of adults (N=61) who met the criteria for AD. Patients underwent a baseline assessment, a 4-week waitlist period, 5 weekly treatment sessions, a postintervention assessment at week 9, and a 4-month follow-up assessment.

During the first treatment session, patients received propranolol 1 mg/kg under supervision. At following sessions, patients were reminded to take the study drug 1 hour prior to the 25-minute appointment in which patients recalled an event where they were romantically betrayed. The effect of propranolol on memory reactivation was assessed using the Impact of Event Scale-Revised (IES-R) instrument.

The study population comprised 72.13% women with a mean age of 42.77 (SD, 12.76) years. Betrayal events occurred a mean of 3.87 (SD, 5.83) years prior to the study. The event was infidelity or deception for 70.49% of patients; 44.26% of patients had a lifetime history of depression; and 29.51% of patients had a lifetime history of anxiety, respectively.

[T]his study provides the required theoretical and methodological blueprint for the planning and execution of randomized trials that include additional control conditions.

Compared with the baseline assessment, 90.91% of patients had moderate to no improvement in IES-R scores during the waitlist period. During the treatment phase, a clinically meaningful change from baseline occurred among 85.42% of patients.

In the segmented regression analysis, significant effects from treatment phase time (β, -5.17; P <.001), the time-by-phase interaction (β, -5.32; P <.001), level effect at week 5 (β, -11.93; P <.001), and level effect at week 9 (β, -33.20; P <.001) were observed on total IES-R scores.

Time had a significant effect on IES-R subscales of intrusion (F[1.71,80.54], 114.13; P <.001), avoidance (F[1.47,68.99], 75.23; P <.001), and hypervigilance (F[2,94], 66.99; P <.001). It also significantly affected Hopkins Symptom Checklist-25 (HSCL-25) total scores (F[2,92], 66.99; P <.001), and depression (F[2,92], 73.02; P <.001) and anxiety (F[2,94], 31.64; P <.001) subscales.

At the 4-month follow-up, no significant change in IES-R (P =.649) or HSCL-25 (P =.534) total scores were observed, suggesting an enduring effect on AD symptoms.

A limitation of the study is the use of the waitlist period as the comparator group instead of an independent cohort.

Study authors concluded, “This paper is the first to address the unmet need for an empirically validated treatment for AD, namely with memory reactivation under propranolol. As such, this study provides the required theoretical and methodological blueprint for the planning and execution of randomized trials that include additional control conditions. Such studies are needed, as AD is a psychological disorder that remains a highly prevalent, yet largely understudied.”

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Lonergan M, Saumier D, Pigeon S, Etienne PE, Brunet A. Treatment of adjustment disorder stemming from romantic betrayal using memory reactivation under propranolol: a open-label interrupted time series trial. J Affect Disord. 2022;317:98-106. doi:10.1016/j.jad.2022.08.082