How much alcohol is in ketamine's antidepressant action?

Abstract

Ketamine is approved to start and maintain anaesthesia or analgesia. Ketamine is also known to be neurotoxic and an old drug of abuse. Numerous studies have proven a rapid and strong antidepressant response (AR) following parenteral sub-anaesthetic ketamine doses when applied the first time to patients with treatment resistant unipolar or bipolar major depression. This rapid and robust AR is encouraging, though short-lived (usually up to seven days). There is growing evidence that repeated und escalating ketamine administrations exert longer-lasting AR than single infusions. Yet, the clinical studies and follow-ups are still too short-lasting to get useful information about ketamine's liability to be addictive and neurotoxic after repeated or even prolonged administrations to severely depressed patients. In this vein, it could be worth to have a look at a couple of pharmacological features that ketamine shares with alcohol being presented here. In essence, there are striking similarities between ketamine and alcohol particularly in terms of modulating glutamatergic and dopaminergic signaling in cortico-limbic brain areas involved in learning, reward and mood regulation, thereby, probably mediating both, AR as well as the development of addiction. Moreover, moderate amounts of both drugs have comparable immunoinhibitory effects hypothesized to be involved in AR, too.