Psychiatric patients are high-risk patients for the development of pharmacokinetic drug-drug interactions (DDIs), leading to highly variable (victim) drug serum concentrations. Avoiding and targeting high-risk drug combinations could reduce preventable adverse drug reactions (ADRs). Pharmacokinetic cytochrome P450 (CYP)-mediated DDIs are often predictable and, therefore, preventable. The retrospective, longitudinal analysis used informations from a large pharmacovigilance study (Optimization of pharmacological treatment in hospitalized psychiatric patients study, study number 01VSF16009, 01/2017), conducted in 10 psychiatric hospitals in Germany. Medication data were examined for the co-prescription of clinically relevant CYP inhibitors or inducers and substrates of these enzymes (victim drugs). In total, data from 27,396 patient cases (45.6% female) with a mean (mean ± standard deviation (SD)) age of 47.3 ± 18.3 years were available for analysis. CYP inhibitors or inducers were at least once prescribed in 14.4% (n = 3946) of the cases. The most frequently prescribed CYP inhibitors were melperone (n = 2504, 28.1%) and duloxetine (n = 1324, 14.9%). Overall, 51.0% of the cases taking melperone were combined with a victim drug (n = 1288). Carbamazepine was the most frequently prescribed CYP inducer (n = 733, 88.8%). Combinations with victim drugs were detected for 58% (n = 427) of cases on medication with carbamazepine. Finally, a DDI was detected in 43.6% of the cases in which a CYP inhibitor or inducer was prescribed. The frequency of CYP-mediated DDI is considerably high in the psychiatric setting. Physicians should be aware of the CYP inhibitory and inducing potential of psychotropic and internistic drugs (especially, melperone).
Keywords: Antidepressants; Antipsychotics; Cytochrome P450; Interactions; Pharmacokinetics; Psychiatry.