Risk of Irritability With Psychostimulant Treatment in Children With ADHD

Stuckelman, Zachary D.; Mulqueen, Jilian M.; Ferracioli-Oda, Eduardo; Cohen, Stephanie C.; Coughlin, Catherine G.; Leckman, James F.; Bloch, Michael H.

doi:10.4088/jcp.15r10601

Cited by 34 publications

(18 citation statements)

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“…Interestingly, several drugs used to treat aggression have been reported to induce AB. Among those are benzodiazepines, antidepressants, central stimulants [150–152], and AEDs, among them TPM [153].…”

Section: Other Potential Mechanismsmentioning

confidence: 99%

“…These monoamines are involved in AB [4]. Among central stimulants, particularly amphetamine and its derivatives are associated with irritability [152]. Amphetamines both increase the release and inhibit the reuptake of NE and DA in the synapse.…”

Section: Other Potential Mechanismsmentioning

confidence: 99%

“…In higher doses, they also inhibit 5-HT. High levels of NA and DA and low levels of 5-HT have been suggested to promote aggression and irritability [4, 152].…”

Section: Other Potential Mechanismsmentioning

confidence: 99%

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Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel

Hansen

Ljung

Brodtkorb

et al. 2018

Behavioural Neurology

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Antiepileptic drugs (AEDs) are effective against seizures, but their use is often limited by adverse effects, among them psychiatric and behavioral ones including aggressive behavior (AB). Knowledge of the incidence, risk factors, and the underlying mechanisms of AB induced by AEDs may help to facilitate management and reduce the risk of such side effects. The exact incidence of AB as an adverse effect of AEDs is difficult to estimate, but frequencies up to 16% have been reported. Primarily, levetiracetam (LEV), perampanel (PER), and topiramate (TPM), which have diverse mechanisms of action, have been associated with AB. Currently, there is no evidence for a specific pharmacological mechanism solely explaining the increased incidence of AB with LEV, PER, and TPM. Serotonin (5-HT) and GABA, and particularly glutamate (via the AMPA receptor), seem to play key roles. Other mechanisms involve hormones, epigenetics, and “alternative psychosis” and related phenomena. Increased individual susceptibility due to an underlying neurological and/or a mental health disorder may further explain why people with epilepsy are at an increased risk of AB when using AEDs. Remarkably, AB may occur with a delay of weeks or months after start of treatment. Information to patients, relatives, and caregivers, as well as sufficient clinical follow-up, is crucial, and there is a need for further research to understand the complex relationship between AED mechanisms of action and the induction/worsening of AB.

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Section: Other Potential Mechanismsmentioning

confidence: 99%

Section: Other Potential Mechanismsmentioning

confidence: 99%

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Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel

Hansen

Ljung

Brodtkorb

et al. 2018

Behavioural Neurology

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“…For example, a recent Cochrane Systematic Review of nonrandomized studies found that rates of anxiety, sadness, and irritability with MPH treatment were 18.4%, 16.8%, and 17.2%, respectively (Storebo et al 2018), whereas a Cochrane Systematic Review of randomized controlled trials (RCTs) found no significant effect of MPH on the AEs of ''worried or anxious'' (risk ratio, (Storebo et al 2016). Additional recent meta-analyses and individual studies found that MPH reduced risk of both anxiety (Gurkan et al 2010;Golubchik et al 2014aGolubchik et al , 2014bCoughlin et al 2015;Snircova et al 2016;Pozzi et al 2018) and irritability (Efron et al 1997;Sonuga-Barke et al 2009;Stuckelman et al 2017;Pozzi et al 2018;Winters et al 2018). Our findings illustrate that both scenarios can in fact be at play-MPH may worsen or improve these emotional symptoms, with the key to predicting direction of effect hinging upon baseline anxiety/depression and oppositionality levels.…”

Section: Discussionmentioning

confidence: 99%

Pre-Existing Comorbid Emotional Symptoms Moderate Short-Term Methylphenidate Adverse Effects in a Randomized Trial of Children with Attention-Deficit/Hyperactivity Disorder

Froehlich

Brinkman

Peugh

et al. 2020

Journal of Child and Adolescent Psychopharmacology

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Objective: We sought to ascertain whether baseline anxiety/depression and oppositional defiant disorder (ODD) symptoms impacted the experience of short-term methylphenidate (MPH) adverse effects (AEs) in 7-to 11-year-old children with attention-deficit/hyperactivity disorder (ADHD) (n = 171) undergoing a double-blind MPH crossover trial. Method: The Vanderbilt ADHD Diagnostic Parent Rating Scale measured baseline child anxiety/depression and ODD symptomology. The parent-completed Pittsburgh Side Effect Rating Scale assessed the AEs of anxiety, sadness, and irritability at baseline, on placebo, and on three MPH dosages. For each AE, we evaluated comorbidity main effects, dose main effects, and comorbidity • dose interactions. Results: Baseline anxiety/depression • dose and ODD • dose interactions were significant for the AEs of anxiety, sadness, and irritability. Compared with premedication baseline, these AEs attenuated on MPH for children with initially higher comorbidity symptoms, whereas those with initially lower comorbidity symptoms tended toward no change or increasing AE levels. Conclusion: Premedication anxiety/depressive and ODD symptoms may be important predictors of short-term MPH emotional AEs.

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“…It is reported up to 25–45% 6. While amphetamine-derived psychostimulants increase irritability, methylphenidate (MPH) derivatives significantly decrease the risk of irritability in comparison to placebo 7. However, head-to-head comparison trials between methylphenidate and amphetamine derivatives to examine their effects on irritability is recommended.…”

Section: Introductionmentioning

confidence: 99%

<p>The effect of stimulants on irritability in autism comorbid with ADHD: a systematic review</p>

Ghanizadeh¹,

Molla²,

Olango³

2019

NDT

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Introduction: While there is a very high rate of comorbidity of autism and ADHD, there are controversies about prescribing stimulants in children with autism. This is a systematic review about the effect of stimulants on irritability in children with both autism and ADHD. Methods: A systematic review was conducted to study the possible effect of stimulants on irritability in autism and ADHD using the databases of PubMed, Scopus, EMBASE, and ScienceDirect in September 2018. Eligible clinical trials of stimulants in the treatment of Autism and ADHD without restriction of language were included. The primary outcome was irritability score. The full texts of relevant articles were studied, and their references were scanned for any possible related article. Results: Out of 1,315 citations, there were 26 relevant articles. Of the relevant articles, 16 were not interventional studies and were excluded. There were 10 interventional studies. None of them considered irritability as a main outcome. Also, none of them studied the effect of stimulants on irritability in autism plus ADHD. Current uncontrolled evidence about the association of stimulants with irritability is controversial. Conclusion: The current evidence is not enough to support or discourage the effect of stimulants on irritability in children and adolescents with both autism and ADHD. Well-designed controlled clinical trials need to be conducted for this ignored research area.

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Risk of Irritability With Psychostimulant Treatment in Children With ADHD

Cited by 34 publications

References 0 publications

Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel

Mechanisms Underlying Aggressive Behavior Induced by Antiepileptic Drugs: Focus on Topiramate, Levetiracetam, and Perampanel

Pre-Existing Comorbid Emotional Symptoms Moderate Short-Term Methylphenidate Adverse Effects in a Randomized Trial of Children with Attention-Deficit/Hyperactivity Disorder

<p>The effect of stimulants on irritability in autism comorbid with ADHD: a systematic review</p>

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