Pharmacological treatments for PTSD: where are we in 2020?

Background: Forty years after the introduction of post-traumatic stress disorder (PTSD) in the third edition of the Diagnostic and Statistical Manual of Mental Disorders, only two selective serotonin reuptake inhibitor antidepressants – sertraline and paroxetine – have received approval for its treatment (Bisson & Olff, 2020). While evidence-based manualized psychotherapy approaches are now the first-line treatment for PTSD, they do not benefit all patients and are limited by the lack of availability of trained therapists in the community. Novel pharmacological treatments for PTSD are still critically needed. Objective: To present a narrative review of: (i) potential causes explaining the limited advances in the pharmacological management of PTSD; (ii) novel pharmacological pathways under investigation; and (iii) innovative approaches using pharmacological compounds that build on our current understanding of the fear system. Results: First, therapeutic innovations in the field of pharmacological treatment of PTSD have been limited by: (i) the almost exclusive focus on the monoamine system; (ii) a gap in translating knowledge gained from basic research to clinical research; and (iii) the use of a medical framework in which we sought to administer a drug to compensate for a chronic deficit. Secondly, outside the monoamine system, novel pharmacological pathways of interest have been identified and are under investigation, including the oxytocin (Flanagan et al., 2019), N-methyl-D-aspartate (NMDA), and endocannabinoid systems. Finally, recent efforts have leveraged knowledge gained about fear acquisition and extinction processes, and efforts to manipulate them for therapeutic purposes, using oestradiol, renin–angiotensin blockers, beta-blockers, D-cycloserine, and psychedelic agents (Kelmendi et al. 2016; Thierrée et al., 2020). Conclusions: Future research on the pharmacological treatment of PTSD should not only focus on novel neurotransmitter pathways, but also build on a better understanding of the pathophysiology of cognitive and emotional processes involved in PTSD, to fully and definitively restore functions, rather than compensate for a posited deficit.