Stress commonly precedes the onset of psychiatric illness, especially in young or vulnerable populations. It is always surprising when some individuals experience extreme stress or adversity (e.g., disrupted attachment, maltreatment, sexual or physical abuse) and do not develop psychopathology, but the reasons for resilience are not well understood. There is a large literature on factors that increase susceptibility to psychiatric illness but less on promoting resilience. Recent research in animal models suggests stress resilience is an active process, similar to the physiologic mechanisms that lead to susceptibility, not merely a passive decline in risk factors.

Treatments to increase resilience in humans have primarily included behavioral interventions such as psychotherapy and exercise. Research in mice has found that modulation of the immune system, blockade of stress hormones and genetic manipulation in addition to exercise and an enriched environment have enhanced resilience, but most of these interventions are not yet possible in humans. In humans, antidepressants and other medications are commonly used to treat existing symptoms or to protect against subsequent episodes of illness (Davidson, Pearlstein, & Londborg 2001[D1] ), but it is not known whether these medications can protect against a first episode of illness or increase resilience.

Ketamine is a drug developed in 1962 that is used primarily as an anesthetic, for pain control, sedation and, more recently, as an antidepressant. It induces feelings of dissociation or hallucinations which has led to its recreational use.  Ketamine is typically administered as a single dose with its effects lasting for days or weeks. This made it an ideal drug for this study since its effect on stress resilience could be followed over 3-4 weeks. In psychiatry, there has been emerging research on the use of ketamine in treatment-resistant depression, bipolar disorder and for patients in suicidal crisis. Ketamine produces rapid antidepressant effects after administration, often within 2 hours, and its effects may last several weeks. The first evidence in humans that ketamine might work to prevent PTSD occurred during the Iraq war. In a study of 25,000 service members, approximately half were treated with ketamine for burns and had lower rates of PTSD (27%) as compared with those who had not received ketamine (46%) (McGhee, Maani, Garza, Gaylord, & Black, 2008), although these findings were not replicated in a subsequent study (McGhee, Maani, Garza, et al. 2014). A recent randomized controlled trial of chronic PTSD in adults shows rapid reduction of symptoms after a single dose of ketamine (Feder, Parides, & Murrough, 2014). Ketamine has not been studied in children for psychiatric purposes, but a recent case report documents its beneficial effect in a child with PTSD, severe aggression and emotional dysregulation who demonstrated sustained behavioral improvement for 8-13 days after receiving ketamine for two medical procedures (Donoghue, Roback, & Cullen, 2015).

Davidson, J., Pearlstein. T., Londborg, P et al. (2001). Efficacy of sertraline in preventing relapse of posttraumatic stress disorder: Results of a 28-week double-blind, placebo-controlled study. American Journal of Psychiatry; 158:1974-1981.

Feder, A., Parides, M.K., Murrough, J.W. et al. (2014). Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder: A randomized clinical trial. JAMA Psychiatry. 71(6):681-8. doi: 10.1001/jamapsychiatry.2014.62.