A study of people with treatment-resistant depression found that four infusions of the antidepressant ketamine led to an improvement in cognitive functioning that persisted for five weeks. These improvements appeared to be independent of the 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 lack of interest or pleasure in activities. It negatively affects several aspects of daily life, including sleep, appetite, and concentration. According to the World Health Organization, approximately 322 million people worldwide suffer from depression.
Typical treatments involve a combination of therapy, medication, and lifestyle changes. However, for about 30% of people, symptoms of depression persist even after two or three rounds of treatment. These people are considered to have treatment-resistant depression. Statistics indicate that your risk of disability and suicide is significantly higher than that of people with treatable forms of depression. Therefore, finding ways to address treatment-resistant depression is a topic of fundamental 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 administering ketamine in specific doses lower than the dose necessary for its anesthetic effect reduces symptoms of depression in 60%-70% of people with ketamine syndrome. Down resistant to treatment. depression. Other studies have indicated that it could also have an effect on cognitive decline, which is one of the core symptoms of depression.
Study author Artemis Zavaliangos-Petropulu and his colleagues wanted to examine whether ketamine infusions at doses lower than those needed to produce anesthetic effects could positively affect the cognitive functions of people with treatment-resistant depression. 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 experienced a depressive episode and had failed to respond to at least two antidepressant treatments. Eligible participants were between 20 and 64 years old, diagnosed with unipolar or bipolar depression, and had moderate or severe depressive symptoms at the start of the study.
Participants received ketamine infusions of 0.5 mg/kg, diluted in 60 cm³ of saline, administered intravenously over 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 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 improvement in general neurocognitive performance and in specific functions persisted five weeks after treatment.
The severity of depression symptoms also decreased after all 4 ketamine treatments, but began to increase again 5 weeks after treatment.
“We demonstrated the cognitive safety and procognitive effects of serial ketamine treatment that were maintained 5 weeks after the end of four serial infusion treatments,” the study authors concluded. “Furthermore, we found that the brain processes that lead to improvements in inhibition are related to those that lead to a successful antidepressant response after ketamine treatment. “In contrast, improvements in other neurocognitive functions, including processing speed, episodic memory, working memory, and attention, over the course of treatment occurred independently of 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 taken into account. It should be noted that the study did not include a control group and the participants knew the characteristics of the treatment they were receiving. The researchers note that participants were not told to expect changes in cognitive functioning, but despite this, the study design does not allow definitive cause-and-effect conclusions to be drawn from the results.
Furthermore, participants completed the same test battery at 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 article, “Neurocognitive effects of serial subanesthetic 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.
