This study presents a continuous hydrothermal process based on the supercritical water (ScW) technology for the treatment of pharmaceutical contaminants in wastewater. Using a simulated wastewater as feedstock, which was prepared with 5 psychoactive drugs (sertraline, paroxetine, zolpidem, escitalopram, and clonazepam), the impact of temperature, feed flow rate, and concentration of H2O2 in the degradation of organic matter was investigated. Thermodynamic aspects of the process were also assessed. The optimal conditions of treatment were at a temperature of 692.8 °C, feed flow rate of 6.6 mL/min, and H2O2 concentration in terms of oxidant coefficient (Ox. C.) of 1.03. Under these conditions, the experimental test achieved a total organic carbon removal efficiency (%RTOC) of 85.9 ± 0.5 %. Biochemical oxygen demand (BOD) and chemical oxygen demand (COD) concentrations decreased from 559.0 and 1118.4 mg/L to 66.0 and 152.5 mg/L, respectively. The liquid phase was also assessed by toxicity assays against Artemia salina microcrustaceans. For the gaseous phase, hydrogen was identified as the main component (57.7 %). Additionally, an assessment of the energy efficiency of the process scale-up was investigated. The ScW process showed a promising potential for large-scale continuous operations as an energy-efficient solution for wastewater treatment and valorization due to the concomitant production of H2-rich gas.