Key Takeaways

  • Nonanxious patients responded significantly better to the lowest ketamine dose that was tested than participants with anxiety did
  • Forty minutes after the start of ketamine infusion, people with anxious depression experienced a lower level of dissociative symptoms as compared to subjects without anxious depression
  • Mass General researchers have found ketamine to be an effective choice for some patients with treatment-resistant depression

About half of patients with major depression also suffer with anxiety, making their disorder particularly difficult to treat.

The anesthetic ketamine has become popular over the past decade as a remedy for depressed patients who have become resistant to standard treatments, but its effectiveness in treating anxious depression was unclear.

Researchers at Massachusetts General Hospital set out to determine the effectiveness of intravenous ketamine at four different doses in treatment-resistant depression, including anxious depression. They compared the drug to the sedative midazolam, and when all four treatment groups were combined, they found that ketamine was an equally effective choice.

Methodology of the Study

The study, which enrolled 99 patients, was led by Mass General research fellow Naji Salloum, MD, and George Papakostas, MD, director of Treatment-Resistant Depression Studies in the Depression Clinical and Research Program. The study was sponsored by the National Institute of Mental Health's Rapidly Acting Treatments for Treatment-Resistant Depression (RAPID), which is a research program that promotes the development of fast-acting therapies for treatment-resistant depression.

The patients in the trial ranged in age from 18 to 70, and 45 of them were defined as having anxious depression as measured by the Hamilton Depression Rating Scale (HAMD), which is widely used to assess the severity of symptoms. Participants either received ketamine at one of the four doses, or midazolam at a dose of 0.045 mg/kg.

From Party Drug to Antidepressant

Ketamine, which has built a reputation as the "party" drug for its popularity among nightclub aficionados, is fast-acting, often producing mood changes within hours, as compared to days for most popular antidepressants. Mass General researchers set out to determine how the patients in the trial were feeling during the first three days after their infusion.

Taken together, our results, as well as results of the two previous reports, highlight the potential role of ketamine in the treatment of anxious depression.

Excerpt from study

Dr. Salloum and colleagues found that this drug is equally effective in treatment-resistant depression with or without anxiety, when measured at both day one and day three after infusion. However, on day three, the nonanxious patients did respond significantly better to the lowest dose tested (0.1 mg/kg) than the anxious group did.

Interestingly, within 40 minutes of receiving the infusion, patients with anxiety experienced fewer "dissociative" symptoms, such as memory loss and a sense of detachment, than participants without anxious depression did. The study authors suggested one reason for that may be that people suffering from anxiety are often treated with the sedative benzodiazepine, which can blunt dissociative symptoms.

There were some other limitations to this study. For instance, the authors tracked changes in a subset of the HAMD measurement scale rather than focusing on the full HAMD-17 score. They did not take HAMD-17 measurements after the baseline testing, and that "prevented us from assessing whether anxiety symptoms improved as rapidly and thoroughly as core depressive symptoms did," they wrote.

Hope for Treatment-Resistant Patients

The Mass General researchers believe their findings are important because there are so few good options for helping patients with depression who have grown resistant to standard treatments. Patients with anxious depression "do not maintain response or remission, and may have a higher side-effect burden compared to subjects with nonanxious depression," the authors wrote.

This new evidence adds weight to two previous studies that explored how the drug affected anxiety levels, the authors noted. One of these trials, which compared the drug to a placebo in treatment-resistant patients, showed ketamine lowered symptoms of depression and lengthened the time to relapse. The second demonstrated significant benefits for the drug over midazolam in anxious and nonanxious depression.

"Taken together, our results, as well as results of the two previous reports, highlight the potential role of ketamine in the treatment of anxious depression," they concluded.

Contributors: George Papakostas, MD and Naji Salloum, MD.