PubMed · 11077021
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S H Zinner. 2000. Tourette disorder.. https://pubmed.ncbi.nlm.nih.gov/11077021/
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Since the first entry of risperidone on to the market in the early 1990s, investigation of the pharmacokinetic behaviour of the compound for which the availability of a bioanalytical method was a condition sine qua non, has received considerable attention. Most of the published methods, however, did not reach the level of sensitivity and selectivity which can be obtained today since the evolution of liquid chromatography-tandem mass spectrometry (LC-MS-MS) towards a routine technique in the bioanalytical laboratory. Therefore, we developed and validated a new LC-MS-MS method for the determination of risperidone and its active metabolite 9-hydroxyrisperidone in human plasma. This paper describes in detail the bioanalytical procedure and summarizes the validation results obtained. In addition, it focuses on the pitfalls one might encounter when developing similar assays. Despite the particular physicochemical characteristics of risperidone and 9-hydroxyrisperidone, the LC-MS-MS method enabled the quantification of both compounds down to 0.1 ng/ml. The method uses a sample preparation step by solid-phase extraction at pH 6 using a mixed-mode phase. In a short chromatographic run, separation of 9-hydroxyrisperidone from the minor metabolite 7-hydroxyrisperidone is achieved. Detection takes place by (turbo)ionspray tandem mass spectrometry in the positive ion mode. The validated concentration range is from 0.100 to 250 ng/ml, using 500 microliter of sample, with accuracy (bias) and precision (coefficient of variation) being below 15%. Although new developments in equipment will allow us to further improve and speed up the method, the assay reported can be used as a routine method to support a wide range of pharmacokinetic studies.
The neuroendocrine aspects of schizophrenia generally receive little attention. This is in marked contrast to depressive disorders, where neuroendocrine issues are central to discussions of pathophysiology and treatment. Although the nature of neuroendocrine dysfunction is less well characterized in schizophrenia than in major depression, a number of neuroendocrine abnormalities have been described. Hypercortisolemia has been extensively documented in patients with schizophrenia, particularly during acute exacerbations, with persistent hypercortisolemia being associated with ventricular enlargement and poor outcome. Similarly, abnormalities in thyroid function, the hypothalamo-pituitary-gonadal axis, growth hormone, prolactin, neurotensin, and other neuroendocrine parameters have also been described in schizophrenia. While the precise neuroendocrine profile of schizophrenia is incompletely characterized, the impact of antipsychotic medications employed in its treatment on various endocrine parameters is better understood. Different conventional and atypical antipsychotics variably contribute to hyperprolactinemia, insulin resistance, and other abnormalities. A critical overview of neuroendocrine abnormalities in schizophrenia is provided and the differential impact of different antipsychotics in contributing to neuroendocrine dysfunction is discussed.
The advent of the newer 'atypical' antipsychotic medications has revolutionized the pharmacologic treatment of schizophrenia and other psychotic disorders. In contrast to the older conventional antipsychotic agents, atypical medications have a broader spectrum of efficacy (greater efficacy in negative, cognitive, and mood symptoms) and a lower risk of extrapyramidal symptoms (EPS) and tardive dyskinesia. Due to concerns surrounding hematological safety and other adverse effects, clozapine is used principally in patients refractory to treatment with other antipsychotic agents. The other three universally available atypical agents (risperidone, olanzapine, and quetiapine) collectively constitute about 70% of all antipsychotic prescriptions in the USA. Despite the broad popularity of these medications and their rapid adoption in general clinical practice, there are limited data on how they compare to each other with regards to their overall efficacy and also as to their efficacy in specific symptom domains. To address this question, two separate analyses were undertaken. First, all published, short-term, randomized, controlled clinical trials of these agents in schizophrenia and schizoaffective disorder were reviewed and the extent of improvement across these agents was compared. While the amount of improvement with a particular agent across its different studies varied, the average improvement was similar for the agents for all efficacy parameters considered. Secondly, all randomized, controlled clinical trials directly comparing two or more of these agents in patients with schizophrenia or schizoaffective disorder were analyzed. Only three such trials (all industry sponsored) were identified; while there were differences in methodology and small differences in efficacy on a minority of measures on which comparisons were undertaken, the preponderance of data suggested no differences in efficacy. While data thus far do not support assertions of differential efficacy between risperidone, olanzapine, and quetiapine, there are clear differences in their side-effect profiles and these are briefly summarized.