Abstract

BackgroundNumerous drugs used in the treatment of psychiatric disorders are substrates of cytochrome P450 enzymes and are potential candidates for drug-drug interactions (DDIs).MethodsClaims data of a German statutory health insurance company from severely mentally ill patients who registered in an integrated care contract from August 2004 to December 2009 were analysed. We measured time periods of concomitant prescription of drugs that have been reported to interact via cytochrome P450, with a focus on drugs acting as strong inhibitors. Such drug-drug exposure (DDE) is an incontrovertible precursor of DDIs. We assessed whether potential DDIs were considered clinically relevant based on the prescribing information of the respective drugs.ResultsAmong all 1221 patients, 186 patients (15.2 %; Clopper-Pearson 95 % confidence interval (CI): 13.3–17.4 %) had at least one DDE prescription, and 58 patients (4.8 %; 95 % CI 3.6–6.1) had at least one DDE prescription involving a strong cytochrome P450 inhibitor. In 59 patients, (4.8 %; 95 % CI: 3.7–6.2 %) five or more DDEs were identified, and five or more DDEs with a strong inhibitor were identified in 18 patients (1.5 %; 95 % CI: 0.9–2.3). The rates of DDEs were 0.27 (Garwood 95%CI: 0.25–0.28) per person-year and 0.07 (95 % CI: 0.07–0.08) for strong-inhibitor DDEs. Four of the ten most frequent DDEs were identified as clinically relevant, and seven of the eight most frequent DDEs involving a strong inhibitor were clinically relevant.ConclusionsThe number of patients with DDEs was not alarmingly high in our sample. Nevertheless, prescription information showed that some prescribed drug combinations could result in serious adverse consequences that are known to weaken or strengthen the effect of the drugs and should therefore be avoided.

Highlights

  • Numerous drugs used in the treatment of psychiatric disorders are substrates of cytochrome P450 enzymes and are potential candidates for drug-drug interactions (DDIs)

  • In this study we focussed on potential DDIs involving cytochrome P450 (CYP450) enzymes, as CYP450 enzymes metabolise many drugs

  • Six CYP450 enzymes are involved in the metabolism of approximately half of all drugs, which emphasises the importance of CYP450s in the analysis of DDIs [13]

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Summary

Introduction

Numerous drugs used in the treatment of psychiatric disorders are substrates of cytochrome P450 enzymes and are potential candidates for drug-drug interactions (DDIs). The risk of DDIs is increased in psychiatric patients [4], as they are often prescribed several concurrent long-term medications [5,6,7,8]. It can be assumed that patients with a psychiatric illness are prone to DDEs and, DDIs because they are often prescribed multi-drug regimens [6]. Millions of patients taking antidepressants experience DDEs, the prevalence of clinically significant DDIs is not clear [20]. In this context, health insurance data can be utilised to investigate the prevalence of DDEs because all medications prescribed in the outpatient sector are documented for reimbursement purposes. As DDEs are an incontrovertible precursor of DDIs, we calculated the frequency of concurrent drug prescriptions and assessed the clinical relevance of the potential DDIs in association with prescription information for the drugs

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