Open-label trial results
In the second study, Dr. Oughli and colleagues evaluated additional key outcomes in geriatric patients treated with IV ketamine as part of a larger open-label late-life trial on TRD.
The secondary analysis of the trial focused on 23 patients (mean age, 71.5 years) who had been initially treated with twice-a-week IV ketamine for 4 weeks.
After the first 4 weeks, patients who had experienced a partial response received an additional 4 weeks of once-weekly IV ketamine.
Overall, 48% of participants achieved a response, and 24% achieved remission of depressive symptoms following the first 4 weeks of twice-weekly treatment. This effect was maintained during the continuation phase of the study.
These findings are consistent with research in younger adults and demonstrate that twice-weekly infusions yield a more sustained antidepressant response than once-weekly infusions, the authors note.
The analysis also showed important increases in psychological well-being scores on the Scale for Suicidal Ideation, improved sleep quality as measured by the Pittsburgh Sleep Quality Index, and overall psychological well-being as shown on the NIH Toolbox Positive Affect on happiness/contentment and the NIH Toolbox General Life Satisfaction scales.
In a previous analysis, published in The American Journal of Geriatric Psychiatry, the researchers also evaluated cognitive function using the NIH Cognitive Battery, which showed that geriatric patients with TRD had significant improvements in a composite of executive functioning and fluid cognition during the 4-week acute treatment period of twice-weekly IV ketamine infusions (Cohen’s d = 0.61) and that those improvements were sustained in the continuation phase of once-weekly infusions for 4 more weeks.
Those results are consistent with ketamine’s known potential procognitive effects in TRD, due to a putative antidepressant mechanism that rescues prefrontal circuit dysfunction through synaptogenesis, the researchers note.
Dr. Oughli said that in both analyses, patients tolerated ketamine well, and there were no serious adverse events.
“Adverse events, including hypertension, dissociated effects, and cravings, were rare and did not prevent the continued use of IV ketamine by older adults. We were able to use clonidine to help manage blood pressure changes seen during the infusions,” she noted.
“These findings are very promising and will need to be confirmed and extended in a larger randomized controlled trial.”
Unsettling for some older patients
George T. Grossberg, MD, director, geriatric psychiatry, Saint Louis University, noted that in his experience, IV ketamine treatment can be unsettling for some older geriatric patients, such as those in their 80s.
“Particularly with some of my older patients, the kind of psychotomimetic properties of ketamine and the out-of-body experiences [with the initial treatment] can be frightening,” he said. “They may be willing to try, but I’ve had more than one patient quit after one treatment because they became so frightened.”
However, the dire nature of TRD and failure to respond to multiple medications and combinations and other strategies may prompt patients to try ketamine as a measure with at least some potential, he noted.
“But there is a high bar for acceptance, especially on the part of older adults and their families, more than for younger people,” he said.
The investigators have disclosed no relevant financial relationships. Dr. Grossberg has received consulting fees from Acadia, Avanir, Biogen, BioXcel, Genentech, Karuna, Lundbeck, Otsuka, Roche, and Takeda.
A version of this article first appeared on Medscape.com.