Change in neurocognitive functioning in patients with treatment-resistant depression with serial intravenous ketamine infusions: The Bio-K multicenter trial.

This nonrandomized, multicenter, open-label clinical trial explored the impact of intravenous (IV) ketamine on cognitive function in adults (n = 74) with treatment-resistant depression (TRD). Patients received three IV ketamine infusions during the acute phase and, if remitted, four additional infusions in the continuation phase (Mayo site). Cognitive assessments using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were conducted at baseline, end of the acute phase, and end of the continuation phase (Mayo site). Results showed a significant 53 % (39/74) remission rate in depression symptoms after the acute phase. In adjusted models, baseline language domain score was associated with a higher odd of remission (Odds Ratio, 1.09, 95 % CI = 1.03-1.17, p = 0.004) and greater improvement in MADRS at the end of the acute phase (β =-0.97; 95 % CI, -1.74 to -0.20; P = 0.02). The likelihood of remission was not significantly associated with baseline immediate or delayed memory, visuospatial/constructional, or attention scores. In the continuation phase, improvements in immediate and delayed memory and attention persisted, with additional gains in visuospatial and language domains. Limitations included an open-label design, potential practice effects, and ongoing psychotropic medication use. Overall, the study suggests cognitive improvement, not deterioration, associated with serial IV ketamine administrations for TRD. These findings encourage future studies with larger sample sizes and longer follow-up periods to examine any potential for deleterious effect with recurrent ketamine use for TRD. Trial Registration: ClinicalTrials.gov: NCT03156504.
Competing Interests: Declaration of competing interest BS received research grant support from Mayo Clinic, National Network of Depression Centers (NNDC), and BD2 (Breakthrough Discoveries for thriving with Bipolar Disorder). SVP has received honoraria for consulting or research funds from the Canadian Institutes for Health Research, Ontario Brain Institute, and Aifred, Janssen, Merck, Mensante, Neonmind, Otsuka, Sage, and Takeda. JLVV has received a grant-in-kind for supplies and genotyping from Assurex Health. EDA has received research support from the following entities in the preceding 12 months: Alkermes, Boehringer-Ingelheim, Janssen, Karuna, Neurocrine Biosciences, Takeda, Teva, and the Vanguard Research Group. EDA also has served on advisory boards or consulted with Alkermes, Clinical Care Options, CMEology, CME Outfitters, Indivior, Karuna, and Teva. FSG has received research grant support from Janssen Therapeutics. WVB has received grant funding or research support from the NIH, AHRQ, National Science Foundation, the Watzinger Foundation, the Myocarditis Foundation, the Blue Gator Foundation, and the Mayo Foundation for Medical Education and Research. MAF has received Grant Support from Assurex Health, Breakthrough Discoveries for Thriving with Bipolar Disorder (BD2), and Mayo Foundation. CME/Travel/Honoraria or Consultant Carnot Laboratories, American Physician Institute. He also has financial interests in Chymia LLC. KEB has received grants from Janssen Pharmaceuticals and has received honorarium as an advisory board member for The Bipolar Roadmap Initiative (Milken Institute for Strategic Philanthropy) and Breakthrough Discoveries for thriving with Bipolar Disorder (BD2). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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