Extrapyramidal Symptoms Are Serious Side-effects of Antipsychotic and Other Drugs

Blair, Donald; Dauner, A

doi:10.1097/00006205-199211000-00018

Cited by 38 publications

(25 citation statements)

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“…Even among the designated "responders", complete remission rates remain low (Bisgaard et al, 2007;Buckley et al, 2001;Mouaffak et al, 2006;Schlaepfer et al, 2013) and patient compliance is compromised by the frequent experience of adverse side effects associated with psychopharmacotherapy (Blair & Dauner, 1992;Zimbroff et al, 1997;Bilder et al, 2002;Siegel et al, 2002;Kroeze et al, 2003;Jaaro-Peled et al, 2009;Abbasi et al, 2010). In the search for novel therapeutic strategies, the Poly(I:C) MIA rodent model has become very attractive in recent years due to its welldocumented validity, thus far assessed mainly in the context of schizophrenia-like phenotypes in rats and mice (Zuckerman et al, 2003;Ozawa et al, 2006;Romero et al, 2007;Meyer, Knuesel, Nyffeler, & Feldon, 2010;Piontkewitz et al, 2012) and recently beginning to be explored in the context of MDD (Khan et al, 2014).…”

Section: The Polyinosinic:polycytidylic Acid Maternal Immune Activatimentioning

confidence: 99%

The Poly(I:C)-induced maternal immune activation model in preclinical neuropsychiatric drug discovery

Reisinger

Khan

Kong

et al. 2015

Pharmacology & Therapeutics

205

199

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Increasing epidemiological and experimental evidence implicates gestational infections as one important factor involved in the pathogenesis of several neuropsychiatric disorders. Corresponding preclinical model systems based upon maternal immune activation (MIA) by treatment of the pregnant female have been developed. These MIA animal model systems have been successfully used in basic and translational research approaches, contributing to the investigation of the underlying pathophysiological mechanisms at the molecular, cellular and behavioral levels. The present article focuses on the application of a specific MIA rodent paradigm, based upon treatment of the gestating dam with the viral mimic polyinosinic-polycytidilic acid (Poly(I:C)), a synthetic analog of double-stranded RNA (dsRNA) which activates the Toll-like receptor 3 (TLR3) pathway. Important advantages and constraints of this animal model will be discussed, specifically in light of gestational infection as one vulnerability factor contributing to the complex etiology of mood and psychotic disorders, which are likely the result of intricate multi-level gene×environment interactions. Improving our currently incomplete understanding of the molecular pathomechanistic principles underlying these disorders is a prerequisite for the development of alternative therapeutic approaches which are critically needed in light of the important drawbacks and limitations of currently available pharmacological treatment options regarding efficacy and side effects. The particular relevance of the Poly(I:C) MIA model for the discovery of novel drug targets for symptomatic and preventive therapeutic strategies in mood and psychotic disorders is highlighted in this review article.

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Section: The Polyinosinic:polycytidylic Acid Maternal Immune Activatimentioning

confidence: 99%

The Poly(I:C)-induced maternal immune activation model in preclinical neuropsychiatric drug discovery

Reisinger

Khan

Kong

et al. 2015

Pharmacology & Therapeutics

205

199

View full text Add to dashboard Cite

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“…The majority of antipsychotics induce CNS side-effects, such as sedation, headaches, dizziness and diarrhea in up to 50% of patients (105). More seriously, the extrapyramidal side-effects of typical antipsychotic drugs, including akathisia, dystonia and drug-induced secondary Parkinsonism, may prevent their chronic use (71). Second-generation atypical antipsychotics can also cause metabolic problems, such as obesity and type II diabetes (106).…”

Section: Resultsmentioning

confidence: 99%

“…Although they are clinically effective, side-effects such as extrapyramidal symptom (EPS) and hyperprolactinemia have limited their chronic application. The more recently developed 'atypical' antipsychotics, such as clozapine, show comparable efficacy to the typical drugs, but without EPS (70,71).…”

Section: Gpcr Blockers In Cancermentioning

confidence: 99%

Repurposing antipsychotics as glioblastoma therapeutics: Potentials and challenges

2016

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Abstract. Glioblastoma multiforme (GBM) is the most common and most lethal primary brain tumor, with tragically little therapeutic progress over the last 30 years. Surgery provides a modest benefit, and GBM cells are resistant to radiation and chemotherapy. Despite significant development of the molecularly targeting strategies, the clinical outcome of GBM patients remains dismal. The challenges inherent in developing effective GBM treatments have become increasingly clear, and include resistance to standard treatments, the blood-brain barrier, resistance of GBM stem-like cells, and the genetic complexity and molecular adaptability of GBM. Recent studies have collectively suggested that certain antipsychotics harbor antitumor effects and have potential utilities as anti-GBM therapeutics. In the present review, the anti-tumorigenic effects and putative mechanisms of antipsychotics, and the challenges for the potential use of antipsychotic drugs as anti-GBM therapeutics are reviewed.

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“…Another tolerability issue commonly associated with antipsychotic medications is the occurrence of EPS [46]. In the first ASPIRE trial, the rates of treatment-emergent EPSrelated adverse events were 14.9 % for the aripiprazole LAI group and 9.7 % for the placebo group [39]; in the second trial, the rates were 21.9 % for the aripiprazole LAI 400 mg group, 11.7 % for the oral aripiprazole group and 12.2 % for the aripiprazole LAI 50 mg group [40].…”

Section: Extrapyramidal Symptomsmentioning

confidence: 99%

Aripiprazole (ABILIFY MAINTENA®): A Review of Its Use as Maintenance Treatment for Adult Patients with Schizophrenia

Shirley¹,

Perry²

2014

Drugs

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Aripiprazole (ABILIFY(®)) is an atypical antipsychotic drug that is proposed to act via partial agonism of dopamine D2 receptors. Trials with oral aripiprazole have shown that, compared with some other atypical antipsychotics, aripiprazole is associated with fewer metabolic disturbances and has a favourable cardiovascular tolerability profile. Recently, an intramuscular long-acting injectable (LAI) depot formulation of aripiprazole (ABILIFY MAINTENA(®)) (aripiprazole LAI) has been approved for use as a treatment for schizophrenia in adults. The efficacy of aripiprazole LAI as a maintenance treatment for schizophrenia has been demonstrated in randomized clinical trials. In the trials, aripiprazole LAI was more effective than placebo, and noninferior to oral aripiprazole, in delaying relapse and in reducing relapse rates in schizophrenia. Aripiprazole LAI was generally well tolerated, with a tolerability profile consistent with that of oral aripiprazole. Thus, aripiprazole LAI is a valuable new treatment option for adult patients with schizophrenia. It may be of particular use for patients stable on oral aripiprazole who would prefer, or are likely to benefit from, a long-acting formulation.

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Extrapyramidal Symptoms Are Serious Side-effects of Antipsychotic and Other Drugs

Cited by 38 publications

References 0 publications

The Poly(I:C)-induced maternal immune activation model in preclinical neuropsychiatric drug discovery

The Poly(I:C)-induced maternal immune activation model in preclinical neuropsychiatric drug discovery

Repurposing antipsychotics as glioblastoma therapeutics: Potentials and challenges

Aripiprazole (ABILIFY MAINTENA®): A Review of Its Use as Maintenance Treatment for Adult Patients with Schizophrenia

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