Allopurinol for the Treatment of Refractory Aggression: A Case Series

Carr, Chelsea N.; Straley, Craig M.; Baugh, Terrence Bradley

doi:10.1002/phar.1943

Cited by 6 publications

(5 citation statements)

References 16 publications

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“…MoCo forms the active site of all eukaryotic molybdenum-dependent molybdoenzymes such as sulphite oxidase, xanthine oxidase/dehydrogenase and aldehyde oxidase [23]. Interestingly, it is reported that allopurinol, an inhibitor of xanthine oxidase, displays anti-aggressive effects, and could effectively treat dementia and schizophrenia patients associated with escalated aggression [24–27]. Thus, Pfs/Mocs1-dependent MoCo pathways may control aggression across phylogeny.…”

Section: Discussionmentioning

confidence: 99%

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The peacefulness gene promotes aggression in Drosophila

Ramin¹,

Li²,

Chang³

et al. 2019

Mol Brain

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Natural aggressiveness is commonly observed in all animal species, and is displayed frequently when animals compete for food, territory and mating. Aggression is an innate behaviour, and is influenced by both environmental and genetic factors. However, the genetics of aggression remains largely unclear. In this study, we identify the peacefulness (pfs) gene as a novel player in the control of male-male aggression in Drosophila. Mutations in pfs decreased intermale aggressiveness, but did not affect locomotor activity, olfactory avoidance response and sexual behaviours. pfs encodes for the evolutionarily conserved molybdenum cofactor (MoCo) synthesis 1 protein (Mocs1), which catalyzes the first step in the MoCo biosynthesis pathway. Neuronal-specific knockdown of pfs decreased aggressiveness. By contrast, overexpression of pfs greatly increased aggressiveness. Knocking down Cinnamon (Cin) catalyzing the final step in the MoCo synthesis pathway, caused a pfs-like aggression phenotype. In humans, inhibition of MoCo-dependent enzymes displays anti-aggressive effects. Thus, the control of aggression by Pfs-dependent MoCo pathways may be conserved throughout evolution.Electronic supplementary materialThe online version of this article (10.1186/s13041-018-0417-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…MoCo is absolutely required for the activity of molybdoenzymes such as sulphite oxidase, xanthine oxidase and aldehyde oxidase [23]. Interestingly, inhibition of MoCo-dependent xanthine oxidase has been shown to display anti-aggressive effects in humans [24–27].…”

Section: Introductionmentioning

confidence: 99%

The peacefulness gene promotes aggression in Drosophila

Ramin¹,

Li²,

Chang³

et al. 2019

Mol Brain

View full text Add to dashboard Cite

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“…Interestingly, in individuals without any psychiatric diagnosis, increased UA levels are associated with temperamental characteristics such as high impulsivity, hyperthymic, and irritable temperament, which are observed in prodromal stages of BD. Allopurinol, besides its antimanic effect as an add‐on treatment, has been reported to reduce aggressive behavior in patients with dementia and refractory aggression in psychiatric inpatients . Additionally, in conditions such as Lesch‐Nyhan syndrome, where excess UA production is present, disinhibition states characterized by impulsivity and irritability are observed .…”

Section: Discussionmentioning

confidence: 99%

Serum uric acid as a predictor of bipolarity in individuals with a major depressive episode

et al. 2018

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| INTRODUC TI ONBipolar Disorder (BD) is one of the top 20 leading causes of disability worldwide. 1 It affects more than 1% of the population, with an estimated lifetime prevalence of 0.6% for type I BD, 0.4% for type II BD, and 1.4% for subthreshold manifestations of BD. 2 Despite the availability of effective treatments, the delay between the onset of BD and its diagnosis and management is often very long, with a pooled interval of almost 6 years. 3 Early diagnosis is difficult in clinical practice because the onset of BD is often characterized by a Objectives: There are no well-established biomarkers to predict the risk of conversion to bipolar disorder (BD) in patients with depression. Given the putative role of purinergic neurotransmission dysfunction in BD, the purpose of our study was to evaluate if higher serum uric acid (UA) levels could predict BD conversion in depressed inpatients. Methods:We reviewed retrospectively the records of subjects hospitalized between June 2007 and June 2010 with a diagnosis of major depressive disorder (MDD) who had undergone routine UA levels testing at admission. At an approximate 10-year follow-up we identified subjects with a subsequent diagnosis of BD. We compared UA levels between the BD-converter and non-BD converter groups, performed Receiver operating characteristic curve analysis to evaluate the prognostic accuracy of serum UA levels and calculated the clinical utility index (CUI) as a risk biomarker for conversion to BD. Results:The study included 250 subjects (55 "BD-converters" and 195 "No BD-converters"). "BD-converters" had significantly higher plasma UA levels compared to "No BD-converters" in their index hospitalization irrespective of gender (males:403.84 ± 91.76 vs 270.81 ± 53.58 µmol/L; U = 94.5, P < 0.001 and females 302.19 ± 52.64 vs 202.69 ± 48.93 µmol/L; t = 10.75, P < 0.001). Serum UA levels showed a very good to excellent accuracy for predicting conversion to BD in inpatients with MDD (area under the curve [AUC]: 0.90; 95% CI: 0.86, 0.94) and had a good to excellent CUI− and a moderate to good CUI+ grading for discriminating BDconverter cases from non-BD converters. Conclusions:Our study suggests that depressed patients with higher levels of serum UA are at greater risk of a subsequent manic or hypomanic episode. The purinergic system could prove a promising path for the search of biomarkers in BD. K E Y W O R D Sbipolar disorder, major depressive disorder, uric acid

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“…Several additional novel treatment strategies and therapies, albeit with less supporting evidence, have been proposed or are under current investigation. A summary of these options is provided in Table …”

Section: Other Therapiesmentioning

confidence: 99%

Management of Self‐injurious Behaviors in Children with Neurodevelopmental Disorders: A Pharmacotherapy Overview

et al. 2019

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Neurodevelopmental disorders (NDDs), a group of disorders affecting ~1–2% of the general population, are caused by changes in brain development that result in behavioral and cognitive alterations, sensory and motor changes, and speech and language deficits. Neurodevelopmental disorders encompass a heterogeneous group of disorders including, but not limited to, Smith‐Magenis syndrome, Lesch‐Nyhan disease, cri du chat syndrome, Prader‐Willi syndrome, pervasive developmental disorders, fragile X syndrome, Rett syndrome, Cornelia de Lange syndrome, and Down syndrome. Self‐injurious behaviors (SIBs) are common in children with NDDs; depending on the specific NDD, the incidence of SIBs is nearly 100%. The management of SIBs in this population is complex, and little high‐quality data exist to guide a consistent approach to therapy. However, managing SIBs is of the utmost importance for the child as well as the family and caregivers. Behavior therapies must be implemented as first‐line therapy. If behavioral interventions alone fail, pharmacotherapy becomes an essential part of management plans. The limited available evidence for the use of common pharmacologic agents, such as second‐generation antipsychotics, and less common agents, such as clonidine, n‐acetylcysteine, riluzole, naltrexone, and topical anesthetics, is reviewed. Additional data from well‐designed studies in children with NDDs are needed to gain a better understanding of this common and troublesome problem including efficacy and safety implications associated with pharmacotherapy. Until then, clinicians must rely on the limited available data, clinical expertise, and ongoing systematic monitoring when managing SIBs in children with NDDs.

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Allopurinol for the Treatment of Refractory Aggression: A Case Series

Abstract: Allopurinol was observed to decrease the number and rate of aggressive events in patients refractory to other treatments.

Cited by 6 publications

References 16 publications

The peacefulness gene promotes aggression in Drosophila

The peacefulness gene promotes aggression in Drosophila

Serum uric acid as a predictor of bipolarity in individuals with a major depressive episode

Management of Self‐injurious Behaviors in Children with Neurodevelopmental Disorders: A Pharmacotherapy Overview

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