Recently, mortality linked to the intake of the antidepressant mirtazapine (MTZ) together with other drugs has been recently detected, and measuring the MTZ concentration in biological fluids has become crucial. The proposed electrode is thought to be the first potentiometric carbon paste electrode for quantifying MTZ in various biological matrices. It is based on the covalent polymerization of the aniline monomers onto the surface of the multi-walled carbon nanotubes (MWCNTs) /TiO 2 nanocomposite to be applied as an ion-to-electron transducer element with 18-crown-6-ether as a recognition element. The MWCNTs/TiO 2 /Polyaniline (PANI) composite was characterized by XRD and FT-IR. The electrode demonstrated a wide linearity range of 1 × 10 À 7 M to 1 × 10 À 2 M with a Nernstian slope of 59.76 � 1.55 mV/concentration decade and a LOD of 3.2 × 10 À 8 M. It was successfully applied for the determination of MTZ in spiked plasma, urine, and artificial cerebrospinal fluid without any significant interference from matrix components, with average recovery, ranged from 97.91 % to 99.31 %.