Physician burnout is a universal dilemma that is seen in healthcare professionals, particularly physicians, and is characterized by emotional exhaustion, depersonalization, and a feeling of low personal accomplishment. In this review, we discuss the contributing factors leading to physician burnout and its consequences for the physician’s health, patient outcomes, and the healthcare system. Physicians face daily challenges in providing care to their patients, and burnout may be from increased stress levels in overworked physicians. Additionally, the healthcare system mandates physicians to keep a meticulous record of their physician-patient encounters along with clerical responsibilities. Physicians are not well-trained in managing clerical duties, and this might shift their focus from solely caring for their patients. This can be addressed by the systematic application of evidence-based interventions, including but not limited to group interventions, mindfulness training, assertiveness training, facilitated discussion groups, and promoting a healthy work environment.

New approaches to the neurobiology of posttraumatic stress disorder (PTSD) are needed to address the reported crisis in PTSD drug development. These new approaches may require the field to move beyond a narrow fear-based perspective, as fear-based medications have not yet demonstrated compelling efficacy. Antidepressants, particularly recent rapid-acting antidepressants, exert complex effects on brain function and structure that build on novel aspects of the biology of PTSD, including a role for stressrelated synaptic dysconnectivity in the neurobiology and treatment ofPTSD. Here, we integrate this perspective within a broader framework-in other words, a dual pathology model of (a) stress-related synaptic loss arising from amino acid-based pathology and (b) stress-related synaptic gain related to monoamine-based pathology. Then, we summarize the standard and experimental (e.g., ketamine) pharmacotherapeutic options for PTSD and discuss their putative mechanism of action and clinical efficacy. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 59 is January 6, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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