Ketamine infusions may improve cognitive function in depressed individuals

A study of individuals with treatment-resistant depression found that four infusions of the antidepressant ketamine led to enhanced cognitive functioning that persisted for five weeks. These improvements appeared to be independent of antidepressant response. The study was published in the Journal of Affective Disorders.

Depression is a mental health disorder characterized by persistent feelings of sadness, hopelessness, and a lack of interest or pleasure in activities. It negatively affects various aspects of daily life, including sleep, appetite and concentration. According to the World Health Organization, about 322 million people in the world suffer from depression.

Typical treatments involve a combination of therapy, medication, and lifestyle changes. However, for about 30% of individuals, the symptoms of depression persist even after two or three times of treatment. These individuals are considered to have treatment-resistant depression. Statistics indicate that their risk of disability and suicide is significantly higher than that of individuals with treatable forms of depression. Therefore, finding ways to address treatment-resistant depression is a topic of critical scientific interest.

A promising new treatment for treatment-resistant depression is ketamine. Ketamine is widely used in medicine as an anesthetic and analgesic, but recent studies indicate that the administration of ketamine in specific doses that are below the dose required for its anesthetic effect reduces the symptoms of depression by 60%-70% of individuals resistant to treatment. depression Other studies have indicated that it could also have an effect on cognitive dysfunctions, which are one of the main symptoms of depression.

The author of the study Artemis Zavaliangos-Petropulo and his colleagues wanted to examine whether infusions of ketamine in doses lower than those necessary to produce the anesthetic effects could positively impact the cognitive functions of individuals with depression resistant to the treatment They were particularly interested in executive function, inhibitory control and attention, language processing and episodic and working memory.

The study included 66 adult participants who had experienced a depressive episode that had not responded to at least two antidepressant treatments. Eligible participants were aged between 20 and 64 years, diagnosed with unipolar or bipolar depression, and had moderate or severe depressive symptoms at the start of the study.

The participants received infusions of 0.5 mg/kg of ketamine, diluted in 60 cm³ of saline, administered intravenously for 40 minutes. Each participant underwent four infusions over a 14-day period. They completed the NIHToolbox Cognition Battery neurocognitive assessment 24 hours after the first and fourth infusions, and again five weeks after the final infusion.

The results indicated that the participants’ working memory, processing speed, episodic memory and overall neurocognitive test performance improved after the four ketamine infusions. There were also modest improvements in language, attention and inhibition. In particular, the increase in general neurocognitive performance and specific functions persisted five weeks after treatment.

The severity of depression symptoms was also reduced after the 4 ketamine treatments, but started to increase again by 5 weeks after the treatment.

“We demonstrated the cognitive safety and procognitive effects of serial ketamine treatment that were sustained 5 weeks after the end of four serial infusion treatments,” concluded the authors of the study. “In addition, we found that brain processes lead to improvements in inhibition related to those that lead to a successful antidepressant response after ketamine treatment. In contrast, improvements in other neurocognitive functions including processing speed, memory episodic, working memory and attention in the course of treatment occurred independently of the change in depressive symptoms.

The study makes a valuable contribution to the scientific understanding of the antidepressant effects of ketamine. However, it also has limitations that must be considered. In particular, the study did not include a control group and the participants were aware of the characteristics of the treatment they were undergoing. The researchers note that the participants were not told to expect changes in cognitive functioning, but despite this, the design of the study does not allow definite conclusions of cause and effect from the results.

Furthermore, participants completed the same battery of tests in multiple assessments and it is possible that (at least some of) the observed effects are consequences of practice rather than treatment. The lack of a control group makes it impossible to differentiate between these two possibilities.

The paper, “Neurocognitive effects of subanesthetic serial ketamine infusions in treatment-resistant depression,” was written by Artemis Zavaliangos-Petropulu, Shawn M. McClintock, Jacqueline Khalil, Shantanu H. Joshi, Brandon Taraku, Noor B. Al -Sharif, Randall T. Espinoza, and Katherine L. Narr.

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