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Controversial drug proves highly effective in treating depression

Medications used to treat depression may have powerful side effects, take weeks or longer to work, or have limited effectiveness in some individuals.

But there is growing excitement - and even surprise - about a new treatment that relieves symptoms of depression in some patients in a matter of minutes, a discovery that could chart a new path in research of the disease.

The medication that is gaining more attention, and respect, in the mental health field is ketamine.

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A small study of 18 patients with bipolar disorder resistant to treatment published this week in the Archives of General Psychiatry found depressive symptoms improved significantly in 71 per cent of those treated with ketamine, compared with a six-per-cent improvement in the group that was given a placebo. Among those given ketamine, depressive symptoms began to improve in as little as 40 minutes.

"The findings are very significant," said Carlos Zarate, chief of experimental therapeutics in the Division of Intramural Research Programs at the U.S. National Institute of Mental Health and lead author of the new study.

The positive effects of one ketamine treatment lasted for about three days, suggesting future clinical treatments be given a few times a week. Although it's a relatively new area of research, previous studies suggest ketamine may be effective on people with other types of depression, not just bipolar disorder.

Ketamine is an anesthetic drug used on animals and sometimes humans. But the preliminary success noted in the study is complicated by the fact ketamine is also used as an illicit street drug known as "special K." People who take it often experience dissociation, or an out of body experience and may also feel numbness, dizziness or have intense hallucinations. It's become an increasingly popular drug of choice in the past decade in Canada. Ketamine has also been used as a date rape drug.

Illicit use of the drug has become so widespread that Health Canada removed it from a list of regulated prescription medications in 2005 and declared it a narcotic in order to restrict how the drug is dispensed.

Despite its notorious record, a growing number of researchers believe ketamine could hold promise for treatment of depression.

"It's really a major breakthrough," said Pierre Blier, professor in the department of psychiatry at the University of Ottawa, Canada Research Chair in psychopharmacology and practising psychiatrist at the Royal Ottawa Hospital.

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Dr. Blier said he has begun treating some treatment-resistant patients with small doses of ketamine to help them snap out of their depression when other medications fail.

Scientists say the drug works by blocking the NMDA receptor, which is responsible for receiving glutamate, a brain chemical. Some studies show glutamate impairment could trigger the development of depression, which explains why blocking the NMDA receptor from receiving the impaired glutamate could improve depressive symptoms. Scientists say ketamine also helps trigger an increased response from the AMPA receptor, which helps control the electrical flow of brain cells.

Dr. Zarate said future research will likely focus on developing ketamine for safe clinical use, and developing a new drug that can create a similar response to ketamine.

While promising, the role of ketamine in depression therapy needs to be approached with great caution, researchers say. The drug is powerful and some long-term side effects may not have been discovered yet. It could also trigger in patients the strong response that has made it such a popular street drug. Dr. Zarate said some patients reported feeling woozy or out of touch with their senses when receiving ketamine intravenously, which took about 40 minutes. The side effects diminished after the drug was administered.

Much is unknown about ketamine and depression, including why it helps some patients but leaves others unaffected. Dr. Zarate said he hopes to uncover some of the mysteries but that in the meantime, he doesn't endorse the clinical use of ketamine.

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