Background: The chronic use of antipsychotics among mentally ill patients requires a careful balance between effectiveness and the consequential adverse effects or drug-drug interactions. Studies characterizing the prescribing patterns of antipsychotics and the potential drug-drug interactions in resource-constrained settings remain scarce. Study Objectives: To characterize the drug use patterns and potential drug-drug interactions (pDDIs) among the mentally ill adult patients at Mathari National Teaching and Referral Hospital in Kenya (MNTRH). Methodology: This was a hospital-based cross-sectional study of 167 patients at MNTRH. A pre-designed semi-structured questionnaire was used to collect the relevant socio-demographic and clinical data, which was coded and entered into Microsoft Excel 2016 for descriptive analysis and then exported to STATA 13. Fischer’s exact and Pearson’s Chi-square tests were used to identify the association between the predictor and outcome variables. A student t-test and one-way analysis of variance were done to compare the effect of various predictor variables on the outcome investigated. A binomial logistic analysis was done by regressing the patients’ profile against the outcome variable to identify the independent predictors. The statistical tests were computed at P≤ 0.05 and a 95% confidence level. Results: The majority of the participants were males (64.7%) and aged below 45 years (76.6%) with a mean age of 36.7 (SD 13.4) years. Most prescriptions contained first-generation antipsychotics (FGAs) (79.2%), and almost half (45.2%) had second-generation antipsychotics (SGAs). Approximately half of the patients (53%) and 38% were on dual and monotherapy antipsychotic, respectively. Only 35.9% of the patients used a standard dose of antipsychotics (≤1000mg of chlorpromazine equivalents), while 53.3% used supramaximal doses. The two most common pDDIs were between olanzapine/carbamazepine and haloperidol/amitriptyline. Patients using supramaximal doses were twice as likely to have pDDIs (OR = 2.23, 95% CI, P=0.023). Having a higher number of FGAs prescribed significantly increased the odds of a patient receiving a supramaximal dose by up to 18 times (P <0.001). The addition of an SGA to a regimen significantly increased the chances of a pDDI (OR=4.01, 95% CI, P<0.001). Conclusion: Psychiatric disorders were mainly managed using FGAs at a much higher frequency than in developed countries. Polypharmacy contributed to patients receiving supramaximal chlorpromazine dose equivalents and adjunct therapy with anticholinergics. Drug-drug interactions can be minimized by avoiding polypharmacy with SGAs and using lower doses of antipsychotics. Close on-treatment monitoring is essential to reduce adverse drug events. Recommendations: Psychiatric disorders should be treated with SGAs as opposed to two or more FGA concurrently to ensure that patients benefit from lower doses of CPZeq, which are associated with a lower risk of extrapyramidal side effects. Future studies should come up with a scaled guideline that informs the clinical efficacy of various doses of CPZeq, particularly involving the FGAs to inform practice and policy.

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