Psychiatric pharmaceuticals are widely distributed in the aquatic environment and have attracted recent attention due to their potential for environmental effects. A robust and reliable in situ passive sampling approach, the diffusive gradients in thin-films (DGT) technique, is developed here to measure 14 psychiatric pharmaceuticals. A new binding material, mixed-mode cation exchange resin (Poly-Sery MCX, 40 μm, CNW, Germany), was used for the first time in DGT and compared to XAD and HLB. Reliable elution efficiencies of the pharmaceuticals from the binding gels were obtained in methanol/ammonia, and diffusion coefficients for all the compounds were determined. The influence of diffusive layer thickness (0.515–2.015 mm), deployment time (3–168 h), and important environmental conditions—pH (3.02–9.45), ionic strength (0.0001–0.5 M), and dissolved organic matter (0–20 mg L–1)—were evaluated. The capacity of XAD, HLB, and MCX gels for binding all the test pharmaceuticals was ∼335 μg per disc, meaning that DGT could theoretically be deployed for over 30 months if there are no competitive effects or confounding factors. The uptake kinetics of psychiatric pharmaceuticals onto MCX gel were much faster than those onto XAD and HLB gels in the first hour. DGT measured concentrations of test pharmaceuticals at two sample points in a river (over 6 days) were comparable to those obtained by grab sampling. This study demonstrates the accuracy and reliability of DGT for measuring psychiatric pharmaceuticals across a wide range of freshwater conditions found in the natural environment.