Subanesthetic Dose Ketamine in Posttraumatic Stress Disorder: A Role for Reconsolidation During Trauma-Focused Psychotherapy?

Despite efforts to develop more effective therapies, PTSD remains a difficult disorder to treat. Insight into the dynamic nature of memory formation and its required molecular machinery can provide an opportunity to target pathological memories for emotionally arousing events. As memories become labile upon retrieval, novel information can update the strength and course of these consolidated memories. Targeting the process of reconsolidation may offer a relevant approach to attenuate fearful and traumatic memories. Specific molecular mechanisms that are required for reconsolidation of arousing information include an intact functioning of the glutamatergic signaling pathways and, more specifically, the integrity of NMDA receptors. Ketamine, a noncompetitive NMDA-receptor antagonist, is receiving increasing interest for a variety of psychiatric indications. This compound can also be an interesting candidate for targeting emotional memories. We explore whether single intravenous infusion of a subanesthetic dose of ketamine can be considered as a viable augmentation strategy for trauma-focused psychotherapy in patients with PTSD. As a consequence, a systematic approach is needed to assess the pharmacodynamic effects of ketamine in relation to both psychotherapy and its pharmacokinetics prior to its application in patient populations. By using a "question-based drug development plan," we can explore such aspects for novel drugs, and we formulated five additional topics that need to be addressed concerning the psychotherapeutic approach and phase orientation of pharmacological assisted psychotherapy.