Ketamine emerged as a novel treatment for certain mental health disorders in 2000 when Berman et al. published a seven patient RCT of intravenous (IV) ketamine compared to a saline placebo showing a reduction in the Hamilton Depression Rating Scale (Ham-D). This was the first suggestion thatketamine could be a benefit for treating mental health disorder and since previous investigations on treatment of mental health disorders have focused on the monoamines (dopamine, norepinephrine and serotonin) this approach may have great potential. Current psychiatric guidelines for treatment of major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and suicidal ideation do not include statements regarding the use of ketamine however research continues to be published. Ketamine is a rapid acting, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that is used as a general anesthetic with analgesic properties used in human and veterinary medicine. The NMDA receptor mediates glutamate excitatory neurotransmission in the brain, and it is hypothesized that a dysfunction in this regulation may play a role in the etiology of depressive symptoms. Ketamine is proposed to help balance the dysfunction, however, by blocking the NMDA receptor; side effects such as vivid dreams and a dissociative effect (where the patient experiences a separation of body and mind) occur frequently. While these side effects are undesirable for the therapeutics, it has created an illicit market for ketamine in certain populations where it is better known as "Special K". Ketaminecan be given through several routes including intravenous push or infusions, intramuscular, intranasal, and orally. Investigations have mainly utilized IV infusions due to the precise dosing and ability to adjust if known side effects occur. Patients who receive ketamine require close monitoring of blood pressure, heart rate, respiratory rate, transcutaneous O2 saturation as well as for emergence reactions (recovery reaction including agitation, hallucinations, dreams and depersonalization) when ketamine wears off. For this reason, current practice is for patients to receive the infusions in clinics with monitoring capabilities, which may be a significant shift in practice from current oral pharmacotherapy where patients can be monitored as outpatients. Given the lack of direction from major psychiatric associations, the utility of ketamine for certain mental health disorders is uncertain. The purpose of this report is to review the clinical effectiveness of intravenous ketamine for the treatment of depression, PTSD, and suicidal ideation, as well as the evidence-based guidelines for its use in these conditions.
Biol Psychiatry. 2013 Jun 15;73(12):1142-55. doi: 10.1016/j.biopsych.2012.11.031. Epub 2013 Jan 29.
Mood disorders such as major depressive disorder and bipolar disorder--and their consequent effects on the individual and society--are among the most disabling and costly of all medical illnesses. Although a number of antidepressant treatments are available in clinical practice, many patients still undergo multiple and lengthy medication trials before experiencing relief of symptoms. Therefore a tremendous need exists to improve currenttreatment options and to facilitate more rapid, successful treatment in patients suffering from the deleterious neurobiological effects of ongoing depression. Toward that end, ongoing research is exploring the identification of biomarkers that might be involved in prevention, diagnosis, treatmentresponse, severity, or prognosis of depression. Biomarkers evaluating treatment response will be the focus of this review, given the importance of providing relief to patients in a more expedient and systematic manner. A novel approach to developing such biomarkers of response would incorporate interventions with a rapid onset of action--such as sleep deprivation or intravenous drugs (e.g., ketamine or scopolamine). This alternative translational model for new treatments in psychiatry would facilitate shorter studies, improve feasibility, and increase higher compound throughput testing for these devastating disorders.