In the United States, 42,773 people committed suicide in 2014. During a previous year, 490,000 hospital visits were related to suicide attempts or self-harming behavior. Worldwide, suicide ranks as one of the top three causes of death among people between 15 and 44. Lacking effective medications, many doctors are at a loss when treating people who contemplate suicide, yet a new study from Massachusetts General Hospital may provide answers.

Repeat intravenous treatment with low doses of ketamine quickly reduced thoughts of self-harm in a small group of patients expressing suicidal feelings for three months or longer, the researchers found.

Like a film noir heroine, ketamine leads a complex double life. Originally developed in 1962, the drug works as a fast-acting anesthetic for humans and gradually found a place in the veterinarian medicine chest as well. Known to lack as deep a sedative effect as other anesthetics, ketamine is used by doctors in special cases, including radiation and burn therapies. As an animal drug, ketamine primarily benefits cats and horses as well as some wildlife.

Meanwhile, the drug maintains a wild, alternate life as a club drug. Special K (as it is known) can be injected, snorted, or simply added to drinks, joints, and cigarettes. Users say it creates a floaty feeling similar in effect to nitrous oxide. At higher doses, the drug can provide hallucinatory or “out of body” experiences; some people find the dreamlike state frightening, others believe it to be spiritual. At a high enough dose, ketamine makes it difficult to move and causes amnesia. For these reasons, it has found its way into the hands of rapists and has been listed as a controlled substance since 1999.

Following half a century of cross-purposes, ketamine is now being studied for a new function: alleviating suicidal thoughts.

The Search For Effective Treatments

Lithium, clozapine, electroconvulsive therapy, and cognitive behavioral therapy all have antisuicidal properties, yet these approved treatments can take weeks or even months to take effect and have either unpleasant side effects or are limited in availability. In the search for a new rapid-acting antidepressant, ketamine has attracted attention in recent years as a likely suspect. However, last month Yale researchers published their review of studies examining the effects of ketamine on suicidal ideation and found the existing data “very preliminary.” The authors called for further controlled trials to permit meaningful assessment and recommendation.

The researchers designed the current study to examine whether low-dose repeat infusions of ketamine might effectively subvert suicidal thinking in patients taking antidepressants. At the same time, they investigated the safety of increased dosages. Led by Dr. Dawn Ionescu of the MGH Department of Psychiatry, the researchers enrolled 14 patients with treatment-resistant depression who had suicidal thoughts for three months or longer.

Over 21 days, each participant received two ketamine infusions a week, with the initial dosage increased after three sessions. Psychological assessments — administered at each visit before, during, and after treatment as well as over three months of follow-up — included measuring the frequency and intensity of suicidal thoughts. Only 12 of the total enrolled participants completed all treatment visits, with one person dropping out due to side effects.

Most of the patients experienced a decrease in suicidal thinking, and seven achieved complete remission by the end of the study period. Of those seven participants, two maintained remission from both suicidal thinking and depression symptoms throughout the follow-up period.

“Ketamine is generally eliminated from the body within 12 to 15 hours, however, we see sustained effects well beyond that. Whether this is due to ketamine, its metabolites, or a combination, is actively being studied,” Ionescu told Medical Daily. While she and her colleagues observed no serious side effects at either dose, they continue to investigate this along with whether or not the drug might exacerbate any side effects of antidepressants.

Ionescu and her colleagues say this study is limited in that it lacks a comparison group of patients taking placebo, however, they are currently performing such a study and remain hopeful for the results. If all goes well, a safe, effective, and easily available treatment for depressed patients at risk of taking their lives may soon become available, granting ketamine at least some reprieve from its bad reputation.

Source: Ionescu DF, Swee MB, Pavone KJ, et al. Rapid and Sustained Reductions in Current Suicidal Ideation Following Repeated Doses of Intravenous Ketamine: Secondary Analysis of an Open-Label Study. Journal of Clinical Psychiatry. 2016.