Product monographs (also known by terms such as Summary of Product Characteristics and Highlights of Prescribing Information, depending on the jurisdiction) provide essential information to ensure the safe and effective use of a drug. Medical practitioners often rely on these monographs for guidance on matters related to pharmacokinetics as well as indications, contraindications, clinical pharmacology, and adverse reactions. The clinical and scientific information found within these documents, forming the basis for decision making, are presumed to be derived from well-designed studies. The objective of this review is to examine the source and validity of the pharmacokinetic data used in establishing the half-lives and times to steady-state reported in the product monographs of second-generation long-acting injectable antipsychotics. Thus, we have critically evaluated the clinical trials from which the pharmacokinetic parameters listed in the product monographs were determined. In many cases, the pharmacokinetic information presented in product monographs is of limited use to clinicians wishing to optimize the effectiveness and tolerability of second-generation long-acting injectable antipsychotics. Under such circumstances, off-label prescribing practices may actually produce better clinical outcomes than if decisions were made based on the product monographs alone.
Retrospective data were collected from 330 individuals who were treated at a tertiary care program for treatment-resistant psychosis between 1994 and 2010. The main objectives were to compare the use of antipsychotic monotherapy to polypharmacy and to characterize within-individual changes in treatment and symptomatology between admission and discharge. At admission, individuals who were prescribed only one antipsychotic were comparable to those who were prescribed at least two antipsychotics with regard to demographics and symptom severity. The use of psychotropic medications other than antipsychotics was also similar between the two groups. However, the magnitude of antipsychotic utilization was greater in individuals who were receiving antipsychotic polypharmacy. In addition, a greater proportion received excessive doses at admission. Similar findings were observed when the two antipsychotic prescribing practices were compared at discharge. Three important patterns were identified when investigating within-individual changes. First, fewer individuals were prescribed more than one antipsychotic at discharge. This was accompanied by a general decrease in the magnitude of antipsychotic utilization. Second, the number of individuals who were prescribed clozapine had increased by discharge. Most who were already prescribed clozapine at admission had their doses increased. Third, improvements in symptomatology were observed across all of the subscales included in the Positive and Negative Symptom Scale (PANSS); 57.9% of individuals experienced a relative reduction in total PANSS scores exceeding 20%. Based on these findings, it is possible to alleviate symptom severity while reducing antipsychotic utilization when patients are treated at a tertiary care program for treatment-resistant psychosis.
BackgroundAntipsychotic drugs can be used to help treat a wide variety of psychiatric disorders. However, specific antipsychotic drugs for any particular patient may need to be changed for a number of different reasons, including a lack of therapeutic efficacy and / or intolerance to medication side-effects. Drug switching may occur through a limited number of established patterns. The nature of these changes is not well characterized in youth, despite their frequent occurrence.MethodsA retrospective analysis of antipsychotic drug switches was conducted on patients who had been admitted as inpatients to a tertiary care child and adolescent psychiatric institute. PharmaNet (a large, central administrative database) records of all medications prescribed in the 52 weeks prior to admission, and then between admission and discharge, were analyzed for switching patterns. Additional data regarding diagnoses were obtained from medical chart review.ResultsPatients represented a diagnostically heterogeneous population, and almost all antipsychotic drugs were administered off-label. In the one year prior to and during admission to the hospital, a total of 31 out of 139 patients switched antipsychotic drugs. The frequency of switching increased closer to the time of admission, and the proportional rate of switching was even higher during hospital stay. The most common switch was from risperidone to quetiapine. Our analysis identified three main patterns of drug switching, all occurring with similar frequency: titrated drug switches, abrupt drug switches and concurrent drug administration.ConclusionsThe present study indicates that antipsychotic drug switching in youth may be relatively common, particularly in the year prior to hospitalization. No specific manner of drug switching predominates. This study also demonstrates the feasibility of using large administrative databases to characterise switching patterns in youth.
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