Ketamine and the potential role for rapid-acting antidepressant medications.

Abstract

Ketamine appears to be the first medication to produce a rapid, although short-lasting, antidepressant response. This finding emerges from two studies: the first was a pilot study published in 2000 by a group of investigators at Yale University [1], and the second was a larger study published last year by an investigative team based at the U.S. National Institute of Mental Health Intramural Research Program [2]. Both studies make the same essential points: 1) depressed patients who had not responded to other antidepressant treatments began to show an antidepressant response within hours of ketamine administration that was significantly better than placebo, 2) for a subgroup of patients (it is difficult to estimate the true size of this group given the small sample sizes for the two studies) this response constituted a remission of their depressive symptoms, 3) that the antidepressant response to a single dose of ketamine persisted for a week or more in some patients, 4) that ketamine administration in these patients was associated with transient cognitive impairments and perceptual changes consistent with psychotigenic effects of ketamine reported in healthy individuals, and 5) overall, ketamine was safe and well-tolerated by the depressed patients studied to date. It is important to note that ketamine is not the first rapid-acting antidepressant treatment identified. That distinction probably belongs to sleep deprivation, whose transient antidepressant effects have been known for over 35 years [3], but whose underlying mechanisms still remain unclear. One can imagine many uses for a rapid-acting antidepressant medication. For example, it might be used to prevent suicide, to reduce the need for hospitalisation for psychiatric patients, to minimise depression-related disability or social disruption, and to simply reduce the distress associated with an episode of depression. However, a medication that induces a transient remission of depression is not, by itself, a treatment for depression. A critical question is whether a rapid-acting antidepressant can play a role within “real world” treatment planning. To this end, we need to know the answers to many questions including: 1) can ketamine be administered repeatedly or combined with another treatment to sustain improvement in depression; 2) does ketamine produce any adverse effects with regard to subsequent antidepressant response; 3) is there any risk of long-lasting psychoses after ketamine administration; 4) may ketamine be administered safely to bipolar depressed patients as well as unipolar depressed patients; 5) are there ways to predict who will respond favourably to ketamine?