Research Shows Ketamine Could Be an Answer for Treatment-Resistant Depression

Generally speaking, most people today either know someone dealing with depression, or have struggled with depression themselves. 

While many individuals can be successfully treated by a combination of medication or talk therapy, there are some who continue to experience symptoms after trying several treatments.

Recent research has highlighted ketamine as a potential treatment for treatment-resistant depression (TRD), so a research team at Mass General, led by Maurizio Fava, MD, decided to explore the effectiveness of various dosages.

Some History on Ketamine and Depression

If you have heard of ketamine, chances are it has been in a negative context due to its reputation for being used illegally as a recreational “club drug.”

However, according to the World Health Organization, it was the most widely-used battlefield anesthetic in the Vietnam war, and has practical uses in anesthesia, sedation and pain management.

Treatment-resistant depression (TRD) is a complicated condition because there are only four FDA-approved drugs used to treat it, and only three approved non-pharmacological treatments.

There has been a steady flow of research showing ketamine provides rapid symptom relief. Most of these studies have used a standard, subanesthetic, intravenous dosage of .5mg/kg, thus leaving researchers with a question about the effectiveness of other dosage levels.

The Research

To test a few treatment options, Mass General researchers created a study that evaluated the effects of four dosages of ketamine and an “active” placebo. The placebo dosage induced side effects similar to ketamine so participants would not know what treatment they were receiving.

Participants were evaluated using a standard depression scale on the day they received the treatment, and again 2, 3, 5, 7, 14 and 30 days later.

Once evaluations were complete, researchers found statistically significant improvement only in participants that received 0.5 mg/kg and 1.0 mg/kg of ketamine, not in those who received the lower doses.

For most participants in the higher-dose groups, the benefits of ketamine treatment began to decrease on the third day after treatment and were no longer detectable after five days.

“These results support the clinical observation that one size – in this case the most studied dose of 0.5 mg/kg – does not fit all, as some patients may require a lower-than-average dose; and each patient needs a tailored treatment plan that may include ketamine, together with other medications and talk therapy. We still do not understand which factors play a role in determining lack of response to treatments or which is the best possible strategy for patients suffering from severe depression.”

– Cristina Cusin, MD, Department of Psychiatry

In the future, researchers hope to explore the efficacy of even lower doses for certain patients; the efficacy of repeat doses; and whether fewer, higher doses of ketamine would be beneficial in reducing the need for frequent treatments.

About the Mass General Research Institute
Massachusetts General Hospital is home to the largest hospital-based research program in the United States. Our researchers work side-by-side with physicians to develop innovative new ways to diagnose, treat and prevent disease.
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