Effects of risperidone on amino acid metabolism, glucose, and kidney function in healthy adults: A pilot randomized controlled trial

D-serine administration prevents kidney damage in murine models of acute kidney injury, and risperidone inhibits the activity of D-amino acid oxidase, which regulate plasma D-amino acid levels. This pilot randomized controlled trial investigated the effects of risperidone on glucose, amino acid metabolism, and kidney function in healthy adults. Healthy adults with a homeostasis model assessment of insulin resistance (HOMA-IR) of ≥ 1.6 and estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73m ² were randomly assigned to the risperidone and control groups. The risperidone group received 0.5 mg/day risperidone for 4 days. The primary outcome was mean change in HOMA-IR on day 5, and the secondary outcomes were changes in D-amino acid levels, eGFR, and urinary albumin. Seven participants were randomized to the risperidone and control groups. The changes in HOMA-IR, eGFR, and urinary albumin on day 5 were not significantly different between the two groups (all p>0.05). Mean changes in plasma D-serine level and urinary D-serine/creatinine ratio were significantly higher in the risperidone group than in the control group (0.2 vs. −0.3 nmol/mL, p=0.03 and 38.2 vs. −25.8 nmol/mL, p=0.01, respectively). Short-term risperidone affects D-serine metabolism without instigating acute adverse effects on kidney or glucose homeostasis in healthy individuals.