Ketamine for Depression, 2: Diagnostic and Contextual Indications

Abstract

There is a substantial body of literature comprising anecdotal material and descriptions of uncontrolled and randomized controlled trials addressing the use of subanesthetic doses of ketamine for the off-label treatment of major depressive episodes. This article examines diagnostic indications for the off-label use of ketamine as an antidepressant and possible contexts in which ketamine may be trialled. Ketamine is indicated in patients who are in a major depressive episode. Most of the research data have been collected from patients with major depressive disorder, but patients with bipolar depression have also been studied. Ketamine is effective in both diagnostic groups, but its benefits are impermanent, perhaps more so in bipolar depression. There are several contexts within this diagnostic framework when a ketamine trial may be considered. These include severe depression and depression that is refractory to conventional antidepressant medication; this is because there is little purpose in trialling an experimental treatment in patients who are less severely ill and those who are antidepressant responsive. More importantly, ketamine has demonstrated efficacy in the rapid reduction of suicidal symptoms and can therefore be trialled when rapid reduction in suicidality is necessary. Likewise, because of its swift and dramatic antidepressant action, it can be trialled in patients in whom improvement is urgently desired in order to allow the patient to attend to pressing life circumstances. Some data suggest that the use of ketamine early during the course of an antidepressant trial, or as anesthesia during electroconvulsive therapy, can improve early antidepressant outcomes. It is not clear whether the presence of psychotic symptoms is a contraindication for ketamine use. Issues related to these indications and contexts are briefly discussed.

Ketamine for Depression, 6: Effects on Suicidal Ideation and Possible Use as Crisis Intervention in Patients at Suicide Risk

“…Therefore, if unanswered questions (Table 2) can be resolved in favor of ketamine, subanesthetic dosing with ketamine may become an important crisis intervention strategy to buy time while other treatments are instituted and take effect. 23 As discussed in earlier articles in this series, 1,2,4 respiratory risks with ketamine are low, even in anesthetic doses, and the drug is relatively safe, even in untrained hands, such as when used in military medical emergencies. An important possibility, then, is that ketamine may be a potential pharmacologic crisis intervention for the suicidal patient even in low-resource, primary care settings in developing countries, where facilities for psychiatric admission, psychotherapy, and ECT are unavailable.…”

“…P revious articles in this column discussed the efficacy, adverse effects, and possible mechanism(s) of action of subanesthetic doses of ketamine in the treatment of depression 1 ; the indications and contexts for the use of ketamine as an off-label antidepressant 2 ; the antidepressant benefits and adverse effects of ketamine and its enantiomers 3 ; issues related to dosing, rate of administration, route of administration, duration of treatment, and frequency of sessions when ketamine is used to treat depression 4 ; and potential pharmacokinetic and pharmacodynamic interactions when ketamine is used as an offlabel treatment for depression. 5 The present article examines the effects of ketamine on suicidal ideation and its possible use as a pharmacologic crisis intervention in patients at suicide risk.…”

A possible role for ketamine in suicide prevention in emergency and mainstream psychiatry

“…Yes, if the recent research on the antidepressant and antisuicidal action of ketamine is considered. There is a growing body of evidence that indicates that, in subanesthetic doses, ketamine has rapid antidepressant[ 14 15 16 17 18 ] and antisuicidal action. In fact, suicide risk is one context within a major depressive episode in which the use of ketamine has been specifically suggested.…”

“…In fact, suicide risk is one context within a major depressive episode in which the use of ketamine has been specifically suggested. [ 15 ] Small studies conducted in emergency department settings have demonstrated that the antisuicidal effect of ketamine may even be apparent within 40 min of treatment. [ 19 20 ]…”

Ketamine for Depression, 5: Potential Pharmacokinetic and Pharmacodynamic Drug Interactions

“…Previous articles in this column considered issues related to the efficacy, adverse effects, and possible mechanism(s) of action of ketamine in the treatment of depression 1 ; discussed indications and contexts for the use of ketamine as an off-label antidepressant 2 ; evaluated the antidepressant benefits and risks of R-ketamine, S-ketamine, and racemic ketamine 3 ; and reviewed issues related to dosing, rate of administration, route of administration, duration of treatment, and frequency of sessions when ketamine is used in subanesthetic doses to treat depression. 4 The present article examines potential pharmacokinetic and pharmacodynamic interactions when ketamine is used as an off-label treatment for depression.…”