A study of individuals with treatment-resistant depression found that four injections of the antidepressant ketamine led to enhanced cognitive performance that persisted for five weeks. These improvements appear to be independent of antidepressant response. The study has been published Journal of Affective Disorders.
Depression is a mental health disorder characterized by 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 worldwide suffer from depression.
Typical treatment includes a combination of therapy, medication, and lifestyle changes. However, about 30% of individuals have persistent symptoms of depression even after two or three rounds of treatment. These individuals are considered to have treatment-resistant depression. Statistics show 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 show that taking ketamine at specific doses below the dose required for its anesthetic effect reduces depressive symptoms in 60% to 70% of treatment-resistant people. : depression. Other studies have shown that it can also affect cognitive impairment, which is one of the main symptoms of depression.
Study author Artemis Zavaliangos-Petropoulou and colleagues wanted to investigate whether ketamine injections at lower doses than needed to produce an anesthetic effect could positively affect cognitive function in 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 had experienced a depressive episode who had failed to respond to at least two antidepressant treatments. Eligible participants were between the ages of 20 and 64, diagnosed with unipolar or bipolar depression, and exhibiting moderate or severe depressive symptoms at baseline.
Participants received infusions of 0.5 mg/kg of ketamine diluted in 60 cc of saline intravenously over 40 minutes. Each participant underwent four infusions over 14 days. 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 showed that the participants’ working memory, processing speed, episodic memory and general neurocognitive test performance improved after four injections of ketamine. There were also modest improvements in language, attention, and inhibition. Notably, improvements in general neurocognitive functioning and specific functions were maintained five weeks after treatment.
The severity of depressive symptoms also decreased after 4 ketamine treatments, but it began to increase again after 5 weeks of treatment.
“We demonstrated cognitive safety and cognitive effects of serial ketamine treatment that persisted 5 weeks after completion of four serial infusion treatments,” the study authors concluded. “In addition, we found that the brain processes that lead to improved inhibition are related to the processes that lead to a successful antidepressant response after ketamine treatment. In contrast, improvements in other neurocognitive functions during treatment, including processing speed, episodic memory, working memory, and attention, occurred independent of changes in depressive symptoms.”
The study makes a valuable contribution to the scientific understanding of ketamine’s antidepressant effects. However, it also has limitations that must be considered. Notably, the study did not include a control group, and participants were aware of the specifics of the treatment they were receiving. The researchers note that the participants were not told to expect changes in cognitive functioning, but even so, the study design does not allow for any clear causal inferences to be drawn from the results.
Additionally, participants completed the same test battery with multiple assessments, and it is possible that (at least some) of the observed effects were due to practice rather than treatment. The lack of a control group makes it impossible to distinguish between these two possibilities.
“Neurocognitive Effects of Subanesthetic Serial Ketamine Injections in Treatment-Resistant Depression” by Artemis Zavaliangos-Petropoulou, Sean M. Espinoza and Catherine L. Nar.
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