Pharmacokinetic-Pharmacodynamic Modeling of S(+)-Ketamine in Fibromyalgia: A Randomized, Double-Blind, Active Placebo-Controlled Trial

Randomized double-blind active placebo-controlled trial (LUMC Department of Anesthesiology, Leiden, Netherlands) of a single 30-minute IV infusion of S(+)-ketamine 0.5 mg/kg vs midazolam 5 mg (active placebo) in adult fibromyalgia patients (ACR 1990 criteria, baseline spontaneous pain VAS ≥5). Target enrollment: 24 (12 per arm). Primary outcomes: spontaneous fibromyalgia pain (VAS, acute phase at 45–180 min) and plasma S-ketamine/S-norketamine concentrations for PKPD modeling. Secondary outcomes: Fibromyalgia Impact Questionnaire (FIQ) and experimental heat pain (thermode VAS), both assessed weekly over 8 weeks of follow-up. Additional registry IDs: NL1296 (new NTR), NL23851.058.08 (CCMO), NL-OMON 22499. Supported by TREND Delft.