Ketamine as treatment for post-traumatic stress disorder: a review

Introduction

Post-traumatic stress disorder (PTSD) is characterised by recurrent intrusive memories, dissociative reactions such as flashbacks, avoidance of trauma-related cues, alterations in cognition and mood, and heightened arousal. The extracted text notes a lifetime prevalence of 8.7% in the United States and a 12-month prevalence of 3.5%. PTSD is more common in certain occupational groups (for example, military veterans, firefighters, police, and emergency medical personnel) and in survivors of rape, combat, captivity, and mass violence. High rates of comorbidity are emphasised: individuals with PTSD are much more likely to meet criteria for other psychiatric disorders, including major depressive disorder (MDD), substance use disorders, and anxiety disorders, and PTSD is associated with substantial functional impairment across social, occupational, and educational domains. Current first-line pharmacotherapy consists of selective serotonin reuptake inhibitors (SSRIs), notably sertraline and paroxetine, with serotonin–norepinephrine reuptake inhibitors (SNRIs) and older antidepressants used in some cases. The authors highlight that many patients do not achieve full remission with available treatments and that augmentation strategies have limited evidence. Ketamine is introduced as a candidate novel therapy: preclinical and clinical observations suggest that stress-related reductions in synaptic connectivity—mediated by glutamatergic systems—might be reversed by NMDA receptor antagonism, and ketamine has been proposed both as a rapid-acting antidepressant and as a possible treatment or prophylactic agent for stress-related disorders including PTSD. The review sets out to summarise the existing preclinical and clinical evidence regarding ketamine’s therapeutic potential and safety in PTSD, noting a relative paucity of literature compared with research in treatment-resistant MDD.