Typical and atypical neuroleptics

Gershanik, Oscar S.; Arevalo, Gonzalo J. Gomez

doi:10.1016/b978-0-444-52014-2.00042-2

Cited by 19 publications

(16 citation statements)

References 148 publications

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“…TD is a movement disorder which typically develops after months or years of AP treatment which often persists even after discontinuation of APs (101). Given the prominent role of APs on dopaminergic receptors and the role of the dopaminergic system in movement control, dopamine receptor genes have been extensively investigated (102).…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Changasi

Shams

Pouget

et al. 2014

Translational Developmental Psychiatry

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Background and purpose: Antipsychotics (APs) are the primary method of treatment for schizophrenia and other psychotic disorders. Unfortunately, lengthy trial-and-error approaches are typically required to find the optimal medication and dosage due to a large interindividual variability with outcome to AP treatment. The literature has shown abundant evidence for a genetic component in individuals' responses to APs. Pharmacogenetic studies analyze specific genetic markers and their association with symptom improvement and occurrence of side effects with APs. This research aims to optimize AP drug treatment by usage of predictive testing and to personalize medicine. Recent findings: This review will highlight the most consistent findings in pharmacogenetics of APs and will update the reader on the clinical implications. This will include how genetic variants modulate AP drug levels, side effects, and therapeutic symptom improvement (i.e. response) to AP treatment. Summary: Several promising findings were obtained implicating gene variants of the dopamine receptor genes in addition to gene variants of serotonin receptors for response and common side effects. Notably, effect sizes appear to be particularly high in the genetics of side effects compared to response. One example is antipsychotic-induced weight gain where the leptin, HTR2C and in particular the melanocortin-4-receptor (MC4R) genes have been implicated in weight gain in children and adolescents. Consistent findings were also obtained for genes implicated in tardive dyskinesia and agranulocytosis. However, the most clinically relevant findings pertain to genes involved in drug metabolism such as the CYP2D6 and CYP2C19 genes which have been included in the first genetic test kits such as the Amplichip †

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Section: Pharmacodynamicsmentioning

confidence: 99%

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Changasi

Shams

Pouget

et al. 2014

Translational Developmental Psychiatry

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“…Rats treated long-term with antipsychotics develop VCMs that share many characteristics typical of tardive dyskinesia, including similarities in appearance, developmental time course, and response to DA drugs (Waddington, 1990). Although rats are considered one of the best animal models, there are limitations as VCMs have been reported to normalize after haloperidol removal in some studies (Marchese et al, 2002;Zhang et al, 2007), whereas antipsychotic-induced tardive dyskinesia in humans may be irreversible (Gershanik and Gómez Arévalo, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…However, their long-term use also leads to the development of abnormal involuntary movements or tardive dyskinesia, which can be very disruptive and eventually debilitating. Dyskinesia is quite common, with an incidence of up to 24% with continued treatment (Correll et al, 2004;Aia et al, 2011;Gershanik and Gómez Arévalo, 2011;Tarsy et al, 2011). Because schizophrenia has a prevalence rate of 0.5%, tardive dyskinesia afflicts a considerable proportion of the population (Saha et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Antipsychotic administration resembles L-DOPA treatment in that both lead to abnormal involuntary movements, possibly due to an enhanced dopaminergic tone (BarrosoChinea and Bezard, 2010;Cenci and Konradi, 2010;Gershanik and Gómez Arévalo, 2011). L-DOPA-induced dyskinesias arise because of the increased conversion of L-DOPA to DA.…”

Section: Introductionmentioning

confidence: 99%

“…Antipsychotics are drugs with dopamine (DA) antagonist properties that form the mainstay of treatment for schizophrenia. They exert their beneficial effect by dampening excess dopaminergic activity, which is currently of unknown pathophysiologic origin (Turrone et al, 2003;Seeman, 2010;Aia et al, 2011;Gershanik and Gómez Arévalo, 2011;Tarsy et al, 2011). Antipsychotics are effective in alleviating psychosis.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats

Bordia

McIntosh²,

Quik

2011

J Pharmacol Exp Ther

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Antipsychotics are an important class of drugs for the management of schizophrenia and other psychotic disorders. They act by blocking dopamine receptors; however, because these receptors are present throughout the brain, prolonged antipsychotic use also leads to serious side effects. These include tardive dyskinesia, repetitive abnormal involuntary movements of the face and limbs for which there is little treatment. In this study, we investigated whether nicotine administration could reduce tardive dyskinesia because nicotine attenuates other drug-induced abnormal movements. We used a well established model of tardive dyskinesia in which rats injected with the commonly used antipsychotic haloperidol develop vacuous chewing movements (VCMs) that resemble human orofacial dyskinesias. Rats were first administered nicotine (minipump; 2 mg/kg per day). Two weeks later, they were given haloperidol (1 mg/kg s.c.) once daily. Nicotine treatment reduced haloperidolinduced VCMs by ϳ20% after 5 weeks, with a significant ϳ60% decline after 13 weeks. There was no worsening of haloperidol-induced catalepsy. To understand the molecular basis for this improvement, we measured the striatal dopamine transporter and nicotinic acetylcholine receptors (nAChRs). Both haloperidol and nicotine treatment decreased the transporter and ␣6␤2* nAChRs (the asterisk indicates the possible presence of other nicotinic subunits in the receptor complex) when given alone, with no further decline with combined drug treatment. By contrast, nicotine alone increased, while haloperidol reduced ␣4␤2* nAChRs in both vehicle and haloperidoltreated rats. These data suggest that molecular mechanisms other than those directly linked to the transporter and nAChRs underlie the nicotine-mediated improvement in haloperidol-induced VCMs in rats. The present results are the first to suggest that nicotine may be useful for improving the tardive dyskinesia associated with antipsychotic use.

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Differential Diagnosis of Movement Disorders in Clinical Practice

Rana

Hedera²

2014

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Typical and atypical neuroleptics

Cited by 19 publications

References 148 publications

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Genetics of antipsychotic drug outcome and implications for the clinician: into the limelight

Nicotine Reduces Antipsychotic-Induced Orofacial Dyskinesia in Rats

Differential Diagnosis of Movement Disorders in Clinical Practice

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