Family History Of Alcoholism Predicts Positive Response To Ketamine

May 13, 2013 · Posted in Potential Treatments 

IVThe drug ketamine can bring about antidepressant effects rapidly when given intravenously, but these effects last only a few days. In a recent study, bipolar depressed patients with alcoholism or a family history of alcoholism in first-degree relatives had a more extended positive antidepressant response to IV ketamine than those without this history, and fewer adverse effects from the treatment. The study, published by David Luckenbaugh et al. from the National Institute of Mental Health in the journal Bipolar Disorders in December 2012, replicates similar findings in patients with unipolar depression, where positive family history of alcoholism also predicted better response and fewer adverse effects from IV ketamine.

Alcohol and ketamine have a common mechanism of action. They are both antagonists of the glutamate NMDA receptor, meaning they limit the effects of glutamate, the major excitatory neurotransmitter in the brain. This suggests a theoretical explanation for why a history of alcoholism might relate to ketamine response.

Editor’s Note: Family history appears to be linked to how patients respond to different mood stabilizers. Lithium works best in those patients with a positive family history of mood disorders (especially bipolar disorder). Carbamazepine works best in those without a family history of bipolar disorder among first-degree relatives. Lamotrigine works best in those with a positive family history of anxiety disorders or alcoholism.

Drugs that are effective in patients with a family history of alcoholism all target glutamate in the brain. Lamotrigine decreases glutamate release, while ketamine reduces glutamate’s effects at the receptor. Both decrease glutamate function or activity. Like lamotrigine, carbamazepine also decreases glutamate release and has good effects in those with a history of alcoholism.

Memantine is another mood-stabilizing drug that is an antagonist of the NMDA receptor, like ketamine and alcohol. It will be interesting to see whether memantine will also be successful in those with a personal or family history of alcoholism.


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