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Psychotropic Use during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Mesoridazine, a piperidyl phenothiazine, is the major active metabolite of thioridazine and is an effective antipsychotic agent. No published epidemiological studies or case reports are available of mesoridazine use in the first trimester. Phenothiazines that have been studied appear to be safe to use during gestation. It was given to pregnant rats and rabbits at doses 12 times in the usual human dose, of mesoridazine during organogenesis, and the frequency of congenital anomalies was not increased among the offspring of rats and rabbits (Van Ryzin et al., 1971).
Clinical Pharmacogenomics Of Human Cyp2d6
Published in Shufeng Zhou, Cytochrome P450 2D6, 2018
Thioridazine is used to treat schizophrenia but has been associated with torsades de pointes and sudden death. Because of the potentially fatal side effects, it is typically reserved for patients who do not respond well to other antipsychot-ics. CYP2D6 and 3A4 convert thioridazine to mesoridazine (Wojcikowski et al. 2006), which correlates weakly with the debrisoquine MR (Berecz et al. 2003; Llerena et al. 2000). There is a weak correlation between corrected QT interval and thioridazine plasma concentrations, debrisoquine MR, and thioridazine/mesoridazine concentrations (Llerena et al. 2002). The metabolites seem to have activity equal to (sul-foridazine) or greater (mesoridazine) than that of the parent, whereas a further ring sulfoxide (thioridazine 5-sulfoxide) produced from thioridazine may be less active as an anti-psychotic, but more arrhythmogenic. After a single dose, the sum of active moieties (thioridazine, mesoridazine plus sulforidazine) is ~1.4-fold higher in PMs, largely attributed to a 4.5-fold increase in thioridazine itself (von Bahr et al. 1991). Consistent with this, the dose-corrected median steady-state plasma thioridazine concentrations are 3.8- and 1.8-fold higher in the presence of no or one active CYP2D6 allele, respectively, compared with two active alleles. Median concentrations of mesoridazine and sulforidazine are not different (Berecz et al. 2003).
The Psychiatric Interview
Published in Mohamed Ahmed Abd El-Hay, Essentials of Psychiatric Assessment, 2018
Thioridazine, and mesoridazine, are no longer available in most countries, and pimozide should be avoided in patients with known heart disease. Ziprasidone should be used cautiously in patients with heart disease, with baseline and follow-up ECG recommended. However, it does not require special monitoring in non-cardiac patients.
Impact of treatment-related discussions on healthcare resource use and costs among patients with severe mental illness
Published in Current Medical Research and Opinion, 2021
Felicia Forma, Eleena Koep, John White, Angela Belland, Heidi Waters, Carolyn Martin
In addition, patients were required to have at least 1 claim for an antipsychotic medication (aripiprazole, asenapine maleate, brexpiprazole, cariprazine, chlorpromazine, clozapine, droperidol, fluphenazine, haloperidol, iIoperidone, loxapine, lurasidone, mesoridazine besylate, molindone, olanzapine, paliperidone, perphenazine, pimavanserin tartrate, pimozide, prochlorperazine, promazine, quetiapine fumarate, risperidone, thioridazine, thiothixene, trifluoperazine, and ziprasidone) during the baseline period and within 60 d after the index date (minimum of 2 claims). Multiple claims were not required to be for the same medication. These inclusion criteria were selected specifically to identify patients with severe symptoms (with diagnosed MDD, bipolar disorder, or schizophrenia) for whom treatment compliance was critical to avoid future acute events. Patients were not excluded if claims for alternative classes of psychotropic therapies, such as antidepressants were also observed.
Phenylalanine 4-monooxygenase: the “sulfoxidation polymorphism”
Published in Xenobiotica, 2020
Stephen C. Mitchell, Glyn B. Steventon
Although the numbers in these early studies were small, they served to provide an indication that individuals may vary in their ability to undertake xenobiotic sulfoxidation and that this could be associated with clinical consequences. Such phenothiazine sulfoxidation is now known to be undertaken by microsomal enzymes, notably the cytochromes P450 (Steventon, 1996; Ziegler, 1982). Indeed, a study of 24 patients receiving thioridazine highlighted one individual who had relatively low plasma levels of the oxidised metabolites, mesoridazine (thioridazine side-chain sulfoxide) and sulforidazine (thioridazine side-chain sulfone), and consequently suffered over-sedation on a conventional dosing regimen. This individual, unlike the majority, was shown to be a poor metaboliser of dextromethorphan and hence have a relative inefficiency in cytochrome P450 2D6 activity (Meyer et al., 1990). The cytochrome P450 superfamily is pursued in other articles in this special edition.
STOPP/START criteria for potentially inappropriate medications/potential prescribing omissions in older people: origin and progress
Published in Expert Review of Clinical Pharmacology, 2020
When I first read the third version of Beers criteria, a number of deficiencies were apparent to me [5]. Firstly, the criteria included several drugs and drug classes that were no longer available in most European drug formularies such as guanethidine, metaxalone, mesoridazine, reserpine, meprobamate, ethacrynic acid and several more. Conversely, some drugs that remain justifiably in use giving significant benefit in selected older people such as amitriptyline, amiodarone, nitrofurantoin, doxazosin, and propranolol were deemed inappropriate which seemed paradoxical. There was no mention of important drug–drug interactions or therapeutic duplication. Of major significance in my mind was the complete absence of common and of important instances inappropriate under-prescribing, what I subsequently referred to as “potential prescribing omissions“ or PPOs. There were several important and commonplace instances of potentially inappropriate medications (or “PIMs“) that were absent from Beers criteria version 3, representing in my view a serious limitation of the criteria. Beers criteria were not organized according to physiological systems, as one finds in most drug formularies. Finally, the criteria appeared to be entirely focused on the US prescriber community and pharmaceutical care milieu, rather than attempting to have wider international relevance.