Academic journal article Current Psychiatry

Is the Evidence Compelling for Using Ketamine to Treat Resistant Depression?

Academic journal article Current Psychiatry

Is the Evidence Compelling for Using Ketamine to Treat Resistant Depression?

Article excerpt

Ms. B, age 31, experienced her first depressive episode at age 24 during her second year of law school. These episodes are characterized by insomnia, sadness, guilt, suicidal ideation, and impaired concentration that affect her ability to function at work and interfere with her ability to maintain relationships. She has no history of mania, hypomania, or psychosis.

Ms. B has approximately 2 severe episodes a year, lasting 8 to 10 weeks. She has failed adequate ([greater than or equal to] 6 week) trials of sertraline, 200 mg/d; venlafaxine XR, 300 mg/d; bupropion XL, 450 mg/d; and vortioxetine, 20 mg/d. Adjunctive treatments were not well tolerated; lithium caused severe nausea and aripiprazole lead to intolerable akathisia. Psychotherapy was ineffective. A trial of electroconvulsive therapy relieved her depression but resulted in significant memory impairment.

Is ketamine a treatment option for Ms. B?

Ketamine, an N-methyl-D-aspartate antagonist, was approved by the FDA in 1970 as a dissociative anesthetic. It proved useful in military battlefield situations. The drug then became popular as a "club drug" and is used recreationally as a dissociative agent. It recently has been used clinically for treating post-operative pain and treatment-resistant depression (TRD).

It has shown efficacy for several specific symptom clusters in depression, including anhedonia and suicidality.

Several small randomized, double-blind, placebo-controlled trials of ketamine--some of which studied TRD--have reported antidepressant effects after a single IV dose of 0.5 mg/kg in depressed patients. (1,2) The response rate, defined as a 50% reduction in symptoms, is reported to be as high as 50% to 71% twenty-four hours after infusion, with significant improvements noted in some patients after just 40 minutes. (1) These effects, peaking at 24 hours, last [greater than or equal to] 72 hours in approximately 50% of patients, but gradually return to baseline over 1 to 2 weeks (Figure (1)). The most common post-infusion adverse effects include:

* dissociation

* dizziness

* blurred vision

* poor concentration

* nausea.

Transient sedation and psychotomimetic symptoms, such as hallucinations, abnormal sensations, and confusion, also have been noted, as well as a small but significant increase in blood pressure shortly after infusion. (1)

Use of repeated doses of ketamine also has been studied, although larger and extended-duration studies are lacking. Two groups (3,4) examined thrice weekly infusions (N = 24) and 1 group (5) studied twice weekly infusions of 0.5 mg/kg for 2 weeks (6 and 4 doses, respectively) (N = 10). With thrice weekly dosing, 79% to 90% of patients showed symptomatic response overall and 25% to 100% of patients saw improvement after the first dose. (3,4) Of the 20 patients who responded, 65% were still reporting improved symptoms 2 weeks after the last infusion and 40% showed response for >28 days. (3,4) With twice weekly dosing, (5) the response rate was 80% in 10 patients, while 5 patients (50%) achieved remission, lasting at least 28 days in 2 patients.

The authors of a recent Cochrane review (6) evaluated ketamine for treating depression and concluded that, although there is evidence for ketamine's efficacy early in treatment, effects are less certain after 2 weeks post-treatment. The Canadian Agency for Drugs and Technologies in Health also conducted an appraisal (7) of ketamine for treating a variety of mental illnesses and similarly noted that, despite evidence in acute studies, (1) the role of the drug in clinical practice is unclear and (2) further comparative studies, as well as longer-term studies, are needed.

Last, the American Psychiatric Association Council of Research Task Force on Novel Biomarkers and Treatments (1) conducted a systematic review and meta-analysis, whose authors concluded that ketamine produces a rapid and robust antidepressant effect that appears to be transient. …

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