Background and Objectives: Patients with schizophrenia are often exposed to polypharmacotherapy, which may lead to drug—drug interactions. The aim of the study was to investigate the prevalence of potential drug—drug interactions (pDDIs) in hospitalized patients with schizophrenia spectrum disorders and to identify factors associated with pDDIs and manifested symptoms and signs. Materials and Methods: This cross-sectional observational study included 311 inpatients admitted to a psychiatric hospital. The LexiComp drug interaction program was used to identify pDDIs in 2014. Factors associated with the prevalence of pDDIs and factors related to clinically observed symptoms and signs were assessed using multivariable regression. In addition, replicate analysis of pDDI was performed using 2021 program updates. Results: The prevalence of pDDIs was 88.7%. Our study showed that more than half of the patients received at least one drug combination that should be avoided. The most common pDDIs involved combinations of two antipsychotics or combinations of antipsychotics and benzodiazepines, which can lead to cardio-respiratory depression, sedation, arrhythmias, anticholinergic effects, and neuroleptic malignant syndrome. The number of prescribed drugs was a risk factor for pDDIs (OR 2.85; 95% CI 1.84–5.73). All groups of clinically observed symptoms and signs were associated with the number of drugs. In addition, symptoms and signs characteristic of the nervous system and psychiatric disorders were associated with antipsychotic dosage (IRR 1.33; 95% CI 1.12–1.58), which could contribute to the development of extrapyramidal syndrome, insomnia, anxiety, agitation, and bipolar mania. The 2021 version of the drug interaction program showed a shift in drug interactions toward a lower risk rating, implying less severe patient management and possibly less alert fatigue. Conclusions: Patients with schizophrenia spectrum disorders are at high risk of developing drug—drug interactions. Optimization of drug therapy, patient monitoring, and use of drug interaction programs could help to prevent pDDIs and subsequent adverse drug events.

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The study aims to identify prescribing and switching patterns of antipsychotics in clinical practice. A 16-month, prospective study was conducted at the Psychiatric Hospital Idrija, Slovenia. Inpatients (N = 311) with schizophrenia spectrum disorders were observed. The causes for switching antipsychotics and switching strategies were analyzed. Analyzing a total of 3954 prescriptions, the collected data confirmed that treatment strategies in this psychiatric hospital are very complex. It was found that 37 percent of inpatients had at least one switch. Moreover, switches that included three or more antipsychotics were detected. The most common causes for switching antipsychotics were adverse reactions and inefficacy or lack of efficacy. Among switching options, abrupt switch was recorded several times. As some patients are receiving several antipsychotics at the same time, it is possible that unusual switching occurs in clinical practice. It seems that the choice of switching strategy is also affected by the cause and urgency for switching an antipsychotic.