Ketamine shows promise for treatment-resistant depression in new study

  • Major depression is a severe mental illness that may cause emotional and physical symptoms and diminished quality of life.
  • Researchers are still seeking to understand the best methods for treating depression that is resistant to medication interventions.
  • A​ new study found that ketamine infusion is comparable to electroconvulsive therapy in treating major depressive disorder.

Depression is a common mental illness. People often respond to treatments that combine medication and therapy, but some depression is resistant to typical techniques.

Experts still seek to understand how to help people with treatment-resistant major depression.

A​ recent study published in The New England Journal of Medicine compared the use of ketamine infusions with electroconvulsive therapy (ECT) — two interventions for treatment-resistant major depression.

The researchers found that using ketamine may be as effective as electroconvulsive therapy in helping people with treatment-resistant depression, with little to no side effects.

Study author Dr. Amit Anand, director of psychiatry translational clinical trials at Mass General Brigham, told Medical News Today:

“​The goal of the study was to investigate whether subanesthetic intravenous ketamine was nearly as good as ECT for treatment-resistant depression. The results were a bit surprising as ketamine did even better than that. Ketamine is good alternative for patients who have been recommended for ECT for treatment of their resistant depression.”

Ketamine vs. electroconvulsive therapy

T​his study was an open-label, randomized, non-inferiority trial. Researchers recruited participants who had treatment-resistant major depression. All participants had been referred for electroconvulsive therapy.

Researchers divided participants into two groups. One group had 195 participants and received ketamine intravenous infusions twice weekly for three weeks. The other group had 170 participants and received electroconvulsive therapy three times weekly for three weeks.

T​hey evaluated the responses to treatment in both groups based on self-reports using a specific scoring method.

A higher score indicated worse depression. They defined a treatment response as a score that decreased by at least 50%. Researchers then followed up over six months among participants who experienced a response.

Both groups experienced an improvement in depressive symptoms. About 55% of the participants in the ketamine group saw improvement, and about 41% of participants in the ECT group saw improvement.

Overall, the ketamine intervention group had fewer problems with memory recall after the three weeks of treatment. The results indicate that ketamine is not inferior to electroconvulsive therapy.

Dr. David Feifel, PhD, neuropsychiatrist and director of the Kadima Neuropsychiatry Institute, not involved in the study, noted to MNT:

“The finding that six sessions of ketamine was no less effective than nine sessions of ECT and produced milder side effects than ECT, has enormous implications for guiding which treatment should be recommended when patients fail to improve with first-line treatments.”

Treatments for major depression

Major depressive disorder (MDD) is a mental illness affecting people’s moods and everyday lives. People with major depression can experience many symptoms, including:

  • emptiness
  • loss of enjoyment in activities
  • suicidal thoughts

People with depression may feel less motivated to complete work tasks or other responsibilities. They may also have difficulty maintaining their relationships, which could be discouraging for everyone involved.

Treatment for depression may involve several approaches, including:

  • antidepressant medication such as selective serotonin reuptake inhibitors (SSRIs)
  • therapy such as cognitive behavioral therapy (CBT)
  • coping techniques
  • developing new, healthier habits

Treating severe depression with ECT

If someone has been unresponsive to two or more medications to treat depression, doctors may diagnose them with treatment-resistant major depression.

Electroconvulsive therapy (ECT) is a type of brain stimulation that is an option for treatment in cases of severe depression. Typically, ECT is not an initial therapy choice. Doctors may recommend it if therapy and medications have been ineffective.

Dr. Feifel explained to MNT:

“ECT is usually used as a treatment of last resort to treat MDD [major depressive disorder] because, it is considered the most effective treatment for this condition, but it is also associated with the highest rate of side effects, such as memory problems, which in some people can persist far beyond the end of the ECT treatments.”

Ketamine for treatment-resistant depression

Ketamine therapy is another more recent approach that may help with treatment-resistant depression.

Dr. Feifel added that psychiatrists and medical professionals had been skeptical about the effectiveness and safety of ketamine. Some, he said, have pushed back against treating major depressive disorder with ketamine.

As more research validates the use and safety of ketamine for therapeutic purposes, the stigma surrounding the drug may eventually fade.

“This study will undoubtedly play a big role in furthering ketamine’s acceptance among those skeptics. Lots more research is still needed, for example, to identify which patients are more likely to benefit from ECT and which from ketamine.”

– Dr. David Feifel, neurobiologist and psychiatrist

Further ketamine research is needed

The study did have key limitations. First, collecting data on depression relies on self-reporting of depressive symptoms, making it harder to generalize results. Second, it only included a small sample size with a short follow-up timeframe.

Researchers acknowledge that electroconvulsive therapy may have more profound effects in certain situations, such as in the inpatient setting. It’s also possible that ECT could have been more effective in this study if participants had received more sessions or used a bilateral placement method as the starting point.

But these interventions may have also increased the risk of adverse events. There was a certain level of flexibility in the treatment methods in this study, and this flexibility could have limited results.

Researchers were also limited by the type of study method they used. Factors like that it was an open-label study, that it didn’t have a placebo, and that they didn’t study maintenance therapy could have all influenced the findings.

Regardless, the study lends further credibility to the use of ketamine in situations of severe depression.

“Further research on more specific populations such as the elderly and bipolar depression as well as in urgent situations such as treatment of depression associated with acute suicidality need to be done (we are now starting such a study). Also, new drugs which can work like ketamine but do not have its associated side effects or possible addictive potential need to be developed.”

– D​r. Amit Anand, psychiatrist and study author

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