Atypical Antipsychotics: Pharmacokinetics, Therapeutic Drug Monitoring and Pharmacological Interactions

Abstract

The development of new "atypical" antipsychotic agents, which are safer than classical neuroleptics and also active against the negative symptoms and neurocognitive deficits caused by the illness, has produced a significant advancement in the treatment of schizophrenia. The atypical (or "second generation") antipsychotics have several therapeutical properties in common, however they can significantly differ with regard to clinical potency and side effects. The main features regarding pharmacodynamics, pharmacokinetics and pharmacological interactions of the most important atypical antipsychotics, namely clozapine, olanzapine, quetiapine and risperidone, are treated herein. Several analytical methods available for the therapeutic drug monitoring of these drugs are also presented, as well as the novel formulations, which can notably improve the therapy of schizophrenia. Other very recent atypical agents, such as ziprasidone, aripiprazole, iloperidone, sertindole and zotepine will also be briefly described.

Application of On-line Electrochemistry/Electrospray/Tandem Mass Spectrometry to a Quantification Method for the Antipsychotic Drug Zotepine in Human Serum

“…1), was developed as a neuroleptic agent, and has been clinically used with relatively few extra-pyramidal side effects. 1,2 Despite the clinical usefulness of zotepine, very few studies have focused on a method for quantifying zotepine, except for an early study by Noda et al 3 The only methods for zotepine determination reported to date involve a complicated and time-consuming extraction procedure, e.g. a gas-liquid chromatographic (GC) method consisting of three liquid-liquid extractions using 1 mL biological samples and the GC-MS method, requiring solid-phase extraction and an evaporation process.…”

The Impact of Cannabis Use on the Dosage of Antipsychotic Drugs for Patients Admitted on the Psychiatric Ward at the University Hospital of the West Indies

“…The subjects prescribed CPZE2 had significantly better outcomes on days three and seven follow-up than subjects prescribed CPZE1. Even though, from the findings, CPZE doses ≤ 300 mg may be the minimal effective doses in patients (21), it appears that this dose is suboptimal and caution should be taken when prescribing doses < 300 mg to male cannabis users with a diagnosis of schizophrenia or schizophreniform disorder. Clinical assessment of the subjects further underscored this finding as most of the subjects who received > 300 mg CPZE attained clinical improvement by day seven compared to only two of eight subjects showing clinical improvement with the lower CPZE dose.…”

Timing and Frequency of Physostigmine Redosing for Antimuscarinic Toxicity

“…Diphenhydramine and quetiapine have relatively short durations of effect [12]. However, in overdose the relatively predictable pharmacokinetics and pharmacodynamics change, making estimates of duration of action difficult [13]. This is particularly applicable when one considers the frequent implication of quetiapine in our patients, which in standard doses has modest muscarinic receptor binding [14].…”