What's the story here?

Growing evidence points to significant anti-depressant effects of several anesthetic agents, including ketamine, nitrous oxide, propofol and isoflurane. These may provide avenues for use as novel antidepressants or lead to development of new agents, supplanting other therapies such as ECT.

Why is this important?

Major depression and its consequences contributes to significant disease burden worldwide. Depression prevalence is increasing globally, with one third suffering treatment-resistant depression, unresponsive to modern antidepressant drugs.

Ketamine appears to produce both a fast antidepressant and antisuicidal effect, persisting for up to 1 week. The effect appears dose-responsive in the 0.1 to 0.75 mg/kg range.

Isoflurane when administered to achieve burst suppression (1.5-2 MAC) may have antidepressant effects in 75% of those treated, and achieved full remission in 50% in one 2013 study, comparable to ECT but with fewer cognitive side effects.

N₂O use in one small pilot study resulted in depression improvement, likely through similar mechanisms as ketamine. Similarly, propofol-induced burst suppression has also shown an antidepressant effect similar in magnitude to isoflurane.

Bottom line: Several anesthetic agents appear to offer significant antidepressant benefits, which may lead to more mainstream use and supplant ECT. Anesthesiologists will be need to be aware of these effects as they become involved in their provision.

summary

• Scott C Tadler and Brian J Mickey.
• Departments of Anesthesiology and Psychiatry.
• Curr Opin Anaesthesiol. 2018 Aug 1; 31 (4): 439-445.

Purpose Of ReviewAfter decades without substantial advances, multiple novel antidepressants show promise against treatment-resistant depression. Interestingly, many of these are anesthetics. The purpose of this review is to discuss the evidence for the antidepressant effects of ketamine, nitrous oxide, isoflurane and propofol and to consider potential clinical, administrative and research implications for anesthesiologists.Recent FindingsKetamine has acute, transient antidepressant and antisuicidal effects. Nitrous oxide has also shown antidepressant efficacy. There are converging preclinical and clinical data that isoflurane (and perhaps propofol), dosed to burst suppression, has relatively rapid, robust and durable antidepressant effects and lacks the adverse effects associated with electroconvulsive therapy (ECT).SummarySeveral anesthetics show promise as novel antidepressants. Ketamine is the most well studied. Anesthetic-induced burst-suppression may provide an alternative to ECT that lacks adverse cognitive effects. Further study is necessary to better understand how these drugs work and how they might be used as effective antidepressant therapy.

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