Review of: Sanacora G et al, JAMA Psychiatry 2017;74(4):399–405. doi:10.1001/jamapsychiatry.2017.0080

Ketamine has become increasingly popular as an off-label medication for rapid onset treatment of refractory depression. Recently, the American Psychiatric Association convened a task force to review the data and come up with some recommendations. The task force reviewed seven double-blind, randomized placebo-controlled trials involving a total of 147 depressed patients.

In terms of patient selection, there are no clearly defined parameters regarding which patients are most appropriate for ketamine. Most evidence is in patients with depressive episodes without psychotic features, and the dose most often shown to be effective is 0.5 mg/kg given intravenously (IV) over 40 minutes. For perspective, the anesthesia dose ranges from 1 to 4.5 mg/kg IV. Anecdotally, the authors note that many ketamine clinics administer doses 2–3 times a week for 2–3 weeks and then taper, depending on patient response. One study showed that doses given 3 times weekly were not more effective than doses given twice weekly. Common side effects after infusion include confusion, blurred vision, and poor coordination. Because approximately 30% of patients in three clinical trials experienced a spike in blood pressure over 180/100 mmHg and heart rates over 110 beats per minute, it’s recommended to do basic monitoring (ECG, BP, O2 sat). Patients at a higher risk of complications (those with cardiovascular disease, those on other depressants, and elderly patients) should be treated at a facility equipped to manage cardiorespiratory events.

Some are reporting the use of lower or higher doses of ketamine, intranasal administration instead of IV, or take-home ketamine, but the authors could not find enough evidence in the literature to endorse these practices. For example, the authors describe trials using lower doses (0.1–0.4 mg/kg IV) or intranasal ketamine (50 mg/ml nasal spray), both of which seemed to show less robust efficacy (see TCPR February 2017 for one prescriber’s anecdotal experience using intranasal ketamine).

Another unknown is how long to use ketamine. Response may be fast, but the studies reviewed by these experts showed relapse rates up to nearly 90% just 4 weeks following the ketamine treatment. We have no long-term safety data either, and the authors share concerns of some of the known risks, such as cognitive impairment or abuse.

TCPR’s Take
Overall, the consensus statement makes one thing clear: We need more data. We recommend considering ketamine in severe, refractory, or suicidal depression without psychotic features, at a dose of 0.5 mg/kg IV over 40 minutes. Ketamine may also be useful in patients who are not good candidates for ECT. Though the rapid response is promising, the effects may be transient, and maintenance infusions may be required for some patients, similar to ECT.