Therapeutic drug monitoring of atypical antipsychotic drugs

Grundmann, Milan; Kacířová, Ivana; Urinovska, R.

doi:10.2478/acph-2014-0036

Cited by 70 publications

(47 citation statements)

References 50 publications

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“…Minocycline, a non-psychotic medication with potent effects in inhibiting microglia, has been suggested as an adjuvant in the treatment of schizophrenia (86). However, atypical antipsychotics induce metabolic and cardiovascular dysfunctions (11, 12). Thus, there is an unmet clinical need for new therapeutic strategies to control inflammation and the progression of schizophrenia.…”

Section: The Inflammatory Hypotheses Of Schizophreniamentioning

confidence: 99%

“…Typical antipsychotics often induce significant psychomotor side effects. Atypical antipsychotics are the usual first-line treatment, although they are associated with metabolic syndrome and an increased cardiovascular risk of death (11, 12). An explanation for the inefficacious treatments is the insufficient knowledge about the etiology of schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

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Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor

et al. 2017

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Schizophrenia is one of the most debilitating mental disorders and is aggravated by the lack of efficacious treatment. Although its etiology is unclear, epidemiological studies indicate that infection and inflammation during development induces behavioral, morphological, neurochemical, and cognitive impairments, increasing the risk of developing schizophrenia. The inflammatory hypothesis of schizophrenia is also supported by clinical studies demonstrating systemic inflammation and microglia activation in schizophrenic patients. Although elucidating the mechanism that induces this inflammatory profile remains a challenge, mounting evidence suggests that neuroimmune interactions may provide therapeutic advantages to control inflammation and hence schizophrenia. Recent studies have indicated that vagus nerve stimulation controls both peripheral and central inflammation via alpha-7 nicotinic acetylcholine receptor (α7nAChR). Other findings have indicated that vagal stimulation and α7nAChR-agonists can provide therapeutic advantages for neuropsychiatric disorders, such as depression and epilepsy. This review analyzes the latest results regarding: (I) the immune-to-brain pathogenesis of schizophrenia; (II) the regulation of inflammation by the autonomic nervous system in psychiatric disorders; and (III) the role of the vagus nerve and α7nAChR in schizophrenia.

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Section: The Inflammatory Hypotheses Of Schizophreniamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor

et al. 2017

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“…They are prescribed much more frequently now and became a first-line agent for schizophrenia as they show less side-effect than the primarily used typical antipsychotic drugs [1]. These drugs are metabolized by the liver extensively and excreted into the urine in animals and humans.…”

Section: Introductionmentioning

confidence: 99%

Sensitive Liquid Chromatography/Tandem Mass Spectrometry Method for the Simultaneous Determination of Risperidone, Olanzapine, Quetiapine, Clozapine, Ziprasidone, Perospirone, Aripiprazole and Blonanserin in Human Serum

Tonooka¹,

Yoshida²,

Tomobe³

et al. 2018

AJAC

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The sensitive method for the simultaneous determination of eight atypical antipsychotic drugs (risperidone, olanzapine, quetiapine, clozapine, ziprasidone, perospirone, aripiprazole and blonanserin) in human serum has been developed based on a high-performance liquid chromatography-tandem mass spectrometry (LC/MS/MS) with electrospray ionization (ESI). The chromatographic separation was performed on a Mightysil-RP-18 MS column (2.0 mm × 150 mm, particle size 3 µm). The mobile phase consisted of 10 mM formic ammonium buffer (pH 6.0) and acetonitrile and was delivered at a flow rate of 0.20 mL/min. The triple quadrupole mass spectrometer was operated in positive ion mode, and multiple reaction monitoring was used for drug quantification. Solid-phase extraction of the eight antipsychotic drugs added to the human serum was performed with an Oasis ® HLB extraction cartridges column. The method was linear for the investigated drugs over the concentration range of 20 -100 ng/mL. The recoveries of these drugs were in the range of 81.3% -140%. The intraday and inter day standard deviation (SD) values for all analytes were <0.10. Therefore, the selectivity, accuracy and precision of this method are sufficient for clinical and forensic studies. This simultaneous screening method will be also applicable to analyze other atypical antipsychotic drugs.

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“…It is widely distributed throughout the body and extensively metabolized in the liver by sulfoxidation mediated mainly by the cytochrome P450 A validated gas chromatographymass spectrometry method for the investigation of quetiapine-related deaths in Greece isoenzyme (CYP3A4) and by oxidation. Quetiapine is binding to plasma proteins (83%) and is renally eliminated with a mean plasma elimination half-life of approximately 7 h [3,15]. It is biotransformated to more than 20 metabolites, where only one, 7-hydroxyquetiapine, possess significant pharmacological activity.…”

Section: Introductionmentioning

confidence: 99%

“…About 73% of a dose appears in the urine and about 20% in the feces, whereas <1% of a dose is excreted unchanged in the urine [16,17]. Peak quetiapine levels are usually observed in blood within 1-2 h and the levels are dose-dependent with a linear relationship within the range of the clinical daily doses (up to 700 mg) [3,15]. The reported in the literature therapeutic blood quetiapine concentrations range from 20 to 600 ng/mL while concentrations higher than 1800 and 4000 ng/mL have been characterized as toxic and lethal, respectively [18,19].…”

Section: Introductionmentioning

confidence: 99%

A validated GC/MS method for the investigation of quetiapine-related deaths in Greece

Papoutsis¹,

Katselou²,

Nikolaou³

et al. 2017

Eur J Forensic Sci

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Objective: Quetiapine is an atypical antipsychotic drug that is used to treat the symptoms of schizophrenia and other psychiatric disorders. During the last years, quetiapine has also been associated with cases of misuse and abuse, and there are strong indications that it possesses an addictive potential. A suitable method is necessary for the toxicological investigation of such cases. Materials and Methods: A simple gas chromatographymass spectrometric method was developed, validated, and applied for the determination of quetiapine in biological fluids during the investigation of quetiapine-related cases. The sample preparation procedure includes solid-phase extraction and silylation using N-methyl-N-tert-butyldimethylsilyl-trifluoroacetamide with 1% tert-butyldimethylsilylchloride. Results: The limits of detection and quantification were 1.50 and 5.00 ng/mL, respectively. The calibration curves were linear up to 2000 ng/mL (R 2 ≥ 0.991) and absolute recovery higher than 81%. Accuracy (intra-and inter-day) was found to be between −11.1 and 12.4%, whereas the precision was found to be <13.3%. The validated method was successfully applied to post-mortem blood samples during the toxicological investigation of 50 quetiapine-related sudden and violent deaths. Quetiapine was determined at toxic levels (>1800 ng/mL) in eight cases and at lower concentrations (5.21-1430 ng/mL) in the other 42 cases. It is remarkable to be mentioned that in all 50 cases one or more drugs were detected along with quetiapine. Conclusions: Quetiapine has been detected with increasing frequency in post-mortem cases in Greece during the last 3 years. This is in accordance with the growing concerns worldwide about the misuse or abuse of the drug and its contribution to the cause of death of quetiapine-related lethal cases. Physicians should be alert about the toxicity of quetiapine, its possible misuse or abuse, and its synergy with other drugs, medicinal or not, especially in patients under multiple drug therapy or drug addicts.

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Therapeutic drug monitoring of atypical antipsychotic drugs

Cited by 70 publications

References 50 publications

Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor

Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor

Sensitive Liquid Chromatography/Tandem Mass Spectrometry Method for the Simultaneous Determination of Risperidone, Olanzapine, Quetiapine, Clozapine, Ziprasidone, Perospirone, Aripiprazole and Blonanserin in Human Serum

A validated GC/MS method for the investigation of quetiapine-related deaths in Greece

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