Bhushan Guragain Medical Director Centre for Victims of Torture Nepal Is reconsolidation impairment a viable treatment option in LMICs for trauma-related memories ? Bhushan Guragain Medical Director Centre for Victims of Torture Nepal

Authors Hanna Kienzler (PI) Duncan Pedersen Alain Brunet RP Sapkota Bhogendra Sharma Bhushan Guragain Jacques Tremblay Melanie Descamps

Introduction Most trauma occur in low- and middle-income countries (LMICs) where mental health resources are scarce. Although pharmacotherapy is recommended for posttraumatic stress disorder (PTSD), side effects lead patients to abandon their treatment1. Psychotherapy can be effective for PTSD but requires highly qualified personnel, is slow, costly and culture-bound2. The β-adrenergic blocker propranolol interferes with the reconsolidation of a recalled traumatic memory, so as to reduce its strength over time3-4-5. We and others have published encouraging results suggesting that reconsolidation impairment can lead to a decrease in PTSD symptoms, including against a placebo6

Hypotheses This study explores the feasibility, cross-cultural social acceptability and efficacy of a new treatment for PTSD in a non-western LMIC country using local mental health resources. With minimal side-effects, we hypothesized that six weekly session of reconsolidation impairment would be well-accepted, and its effectiveness would be non-inferior to the anti-depressant typically recommended to treat PTSD: paroxetine.

Methods Double-blind randomized controlled trial involving three measurement times (pre-, mid- and post-treatment). Men and women Nepalese adults (18-65 y.o.), reporting torture and civil-war related traumatic events were recruited with the help of the CVICT in a rural health-post in Nepal. - Reconsolidation impairment group (n = 23), - Paroxetine-treated group (n = 20).

Week 0 Week 1 Weeks 2-7 Week 8 Weeks 9-12 Week 13 Ss selection Pre-treatment Randomization Treatment visits Mid-study assessment Post-treatment assessment Enrollment Eligibility Formal consent PTSD Diagnosis Medical exam Interviewer-based questionnaires Script of trauma preparation Reconsolidation impairment gp Placebo daily + trauma reactivation procedure weekly under propranolol Visit every 2 weeks for placebo delivery Interviewer-based questionnaires and diagnostic interview Paroxetine gp (classic treatment) Paroxetine daily + trauma reactivation procedure weekly under a placebo Visit every 2 weeks for treatment delivery

Reconsolidation impairment, as a form of therapy, was well accepted by the patients. Moreover, we were able to train local health counsellor in administering the treatment, which attests to its simplicity and social acceptability. Both groups improved equally on all outcome measures. Only a few minor and transient side-effects were reported. Psychological distress and disability decreased significantly whereas quality of life was significantly improved. At the end of the treatment, only one treatment completer was still meeting criteria for PTSD. If replicated, such results suggest that reconsolidation impairment represent a new hope for PTSD care in LMICs

Limitations The follow-up results have yet to be analyzed to ensure that treatment benefits are sustained. An intent-to-treat analysis would be required in addition to analyzing the data from the study completers.

References 1-Marks, D. M. et al. (2008). Paroxetine: safety and tolerability issues. Expert opinion on drug safety, 7(6), 783-794. 2-Tol, W. A., Jordans, J. D., Regmi, S., & Sharma, B. (2005). Cultural challenges to psychosocial counselling in Nepal. Transcultural Psychiatry, 42(2), 317-333. 3-Nader, K., Schafe, G. E., & Le Doux, J. E. (2000). Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature, 406(6797), 722-726. 4-Brunet, A., Orr, S. P., Tremblay, J., Robertson, K., Nader, K., & Pitman, R. K. (2008). Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. J Psychiatr Res, 42(6), 503-506. 5-Przybyslawski, J., & Sara, S. J. (1997). Reconsolidation of memory after its reactivation. Behav Brain Res, 84(1-2), 241-246. 6-Brunet, A., et al. (2011). Trauma reactivation under the influence of propranolol decreases posttraumatic stress symptoms and disorder: 3 open-label trials. J Clin Psychopharmacol, 31(4), 547-550.