Aripiprazole in Children and Adolescents with Conduct Disorder: A Single-Center, Open-Label Study

Ercan, Emre; Uysal, Taciser; Ardıç, Ülkü Akyol

doi:10.1055/s-0031-1286348

Cited by 18 publications

(10 citation statements)

References 16 publications

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“…In a further open-label study, another atypical antipsychotic, aripiprazole, was well-tolerated and associated with significant improvements in symptoms of inattention, hyperactivity/impulsivity, as well as of ODD and conduct disorder (165). In addition, aripiprazole was also associated with significant improvements in delinquent and aggressive behavior.…”

Section: Treatment Of Adhd and Criminal Behaviorsmentioning

confidence: 92%

Attention-deficit hyperactivity disorder (ADHD), substance use disorders, and criminality: a difficult problem with complex solutions

Knecht¹,

Alvaro

Martínez-Raga³

et al. 2015

International Journal of Adolescent Medicine and Health

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The association between attention-deficit hyperactivity disorder (ADHD) and criminality has been increasingly recognized as an important societal concern. Studies conducted in different settings have revealed high rates of ADHD among adolescent offenders. The risk for criminal behavior among individuals with ADHD is increased when there is psychiatric comorbidity, particularly conduct disorder and substance use disorder. In the present report, it is aimed to systematically review the literature on the epidemiological, neurobiological, and other risk factors contributing to this association, as well as the key aspects of the assessment, diagnosis, and treatment of ADHD among offenders. A systematic literature search of electronic databases (PubMed, EMBASE, and PsycINFO) was conducted to identify potentially relevant studies published in English, in peer-reviewed journals. Studies conducted in various settings within the judicial system and in many different countries suggest that the rate of adolescent and adult inmates with ADHD far exceeds that reported in the general population; however, underdiagnosis is common. Similarly, follow-up studies of children with ADHD have revealed high rates of criminal behaviors, arrests, convictions, and imprisonment in adolescence and adulthood. Assessment of ADHD and comorbid condition requires an ongoing and careful process. When treating offenders or inmates with ADHD, who commonly present other comorbid psychiatric disorder complex, comprehensive and tailored interventions, combining pharmacological and psychosocial strategies are likely to be needed.

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Section: Treatment Of Adhd and Criminal Behaviorsmentioning

confidence: 92%

Attention-deficit hyperactivity disorder (ADHD), substance use disorders, and criminality: a difficult problem with complex solutions

Knecht¹,

Alvaro

Martínez-Raga³

et al. 2015

International Journal of Adolescent Medicine and Health

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“…The overall methodological quality of the included non-randomized studies (retrospective chart reviews [34, 36, 48, 50, 52, 63, 67]; other non-randomized studies [33, 35, 37, 43, 45, 46, 49, 51, 53–62, 64–66, 68, 73, 75, 76]) was low to moderate (see Table S3 in the ESM).…”

Section: Resultsmentioning

confidence: 99%

“…For the analysis of the mean EPS incidence, data were provided by 24 studies ( N ), with a total of 1446 pediatric patients ( n ) [25, 27–30, 33, 36, 37, 43, 45, 49–51, 53–56, 58, 60, 61, 63, 65, 68, 74]. Meta-analysis revealed a mean EPS incidence of 17.1 % (95 % CI 0.128–0.223) (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Aripiprazole and Acute Extrapyramidal Symptoms in Children and Adolescents: A Meta-Analysis

et al. 2016

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BackgroundBoth the US FDA and the European Medicines Agency (EMA) have approved aripiprazole for use in adolescents for specific indications. Given the assumed favorable side-effect profile of aripiprazole, its use in children and adolescents has increased for both official and off-label indications (anxiety disorders, eating disorders, personality disorders). However, several cases of children and adolescents with new-onset extrapyramidal symptoms (EPS) after commencing treatment with aripiprazole have been reported, and a more systematic appraisal of this possible risk is lacking.ObjectiveWe conducted a systematic review and a meta-analysis to assess the evidence for acute EPS (acute dystonia, akathisia, Parkinsonism) associated with the use of aripiprazole in children and adolescents.MethodWe searched the MEDLINE and Embase databases (2003–10 April 2016) for clinical trials in pediatric patients (aged 0–18 years) using the keywords ‘aripiprazole’ (regardless of the formulation) and ‘extrapyramidal symptoms’. We evaluated the abstracts of papers using the following exclusion criteria: (1) study design: case report, letter to the editor, editorial, or poster presentation data; (2) unrelated PICOS (population, intervention, comparators, outcomes, study) structure. We performed a meta-analysis, in which we used effect sizes with 95 % confidence intervals (CIs). To examine the homogeneity of the effect size distribution, we used a Q-statistic. When we observed heterogeneity in effect sizes, we assessed the possible influence of moderator variables (age and sex, mean dose, study duration, and method of measuring EPS incidence) and evaluated the suitability of either a fixed or a random model. Finally, we assessed the incidence of EPS in children and adolescents treated with aripiprazole compared with placebo.ResultsAn initial search via PubMed and Embase yielded 328 hits. A manual search of the reference lists of review papers revealed seven additional relevant articles. We included 41 studies, with 2114 pediatric patients, in the meta-analysis. For the analysis of the mean incidence of EPS, data were provided by 24 studies, with a total of 1446 pediatric patients. Meta-analysis revealed a mean EPS incidence of 17.1 % (95 % CI 0.128–0.223). In terms of the incidence of various extrapyramidal side effects, overall, no significant effects of age, sex, mean dose, study duration, or measuring method could be demonstrated. The side effects ‘EPS’, ‘parkinsonism’, and ‘tremor’ were significantly more common in children and adolescents treated with aripiprazole than in those treated with placebo.ConclusionOur meta-analysis provides evidence for a non-negligible incidence of acute EPS in children and adolescents treated with aripiprazole. Although the study has several limitations and further investigation is needed, these findings may help clinicians make more balanced treatment choices and more closely monitor the use of this drug in youth.Electronic supplementary materialThe online version of this article (doi:10.1007/s40...

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“…A more complex case emerges through the investigation of methylphenidate and the atypical antipsychotics, risperidone/paliperidone 47 and aripiprazole, drugs prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) [48][49][50] . FAERS analysis indicates that treatment with risperidone/paliperidone, the latter of which is the main active metabolite of risperidone, increases the frequency of gynecomastia and galactorrhea, while methylphenidate has a low incidence of these ADRs, as do other atypical antipsychotics, such as aripiprazole (Figure 6 Figure 6B).…”

Section: Cc-by-nd 40 International License Peer-reviewed) Is the Autmentioning

confidence: 99%

The Importance of Reverse Translation for Preclinical Off-Target Mitigation: Quantification and Mitigation of Biases in the FDA Adverse Event Reporting System

Maciejewski

Lounkine

Whitebread

et al. 2016

Preprint

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Abstract-The Food and Drug Administration Adverse EventReporting System (FAERS) is the primary source for postmarketing pharmacovigilance. Though potentially highly useful, the database reflects reporting biases, stimulated reporting, and suffers from lack of standardization and the use of multiple drug synonyms. These biases can suggest adverse drug reactions (ADRs) where none exist, and can obscure others that do exist. To decrease the noise in FAERS, and to reinforce important associations, we mapped over 750,000 drug identifiers in FAERS to the normalized chemical structures of their ingredients. This illuminated associations that would not otherwise be apparent, and also allowed a time-resolved analysis of ADR reporting. It also revealed similarities between drugs and adverse events across therapeutic classes, enabling unbiased classification of adverse events, indications, and drugs with similar clinical profiles. For instance, comparison of two selective cyclooxygenase-2 inhibitors, celecoxib and rofecoxib finds distinctive FAERS profiles after time-resolved analysis. We also investigated key idiosyncrasies, such as confusion between drug indications and drug ADRs, which can tar a drug treating a life-threatening disease, like thalidomide's use against myeloma, with a deadly ADR that is likely the result of the disease itself, multiplications of the same report, which unjustifiably increases its apparent importance, and the correlation of reported ADRs with public events, regulatory announcements, and with publications. Comparing the pharmacological, pharmacokinetic, and clinical ADR profiles of methylphenidate, aripiprazole and risperidone, and of kinase drugs targeting the VEGF receptor (VEGF-R2), demonstrates how underlying molecular mechanisms can emerge from ADR co-analysis. The precautions and methods we describe may enable investigators to avoid confounding chemistry-based associations and reporting biases in FAERS, and illustrate how comparative analysis of ADRs can reveal underlaying mechanisms.

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Aripiprazole in Children and Adolescents with Conduct Disorder: A Single-Center, Open-Label Study

Abstract: Aripiprazole is an eff ective and well-tolerated treatment for ADHD and CD symptoms; however, additional studies (specifically, placebo-controlled and double-blind studies) are needed to better defi ne the clinical use of aripiprazole in children and adolescents with ADHD-CD.

Cited by 18 publications

References 16 publications

Attention-deficit hyperactivity disorder (ADHD), substance use disorders, and criminality: a difficult problem with complex solutions

Attention-deficit hyperactivity disorder (ADHD), substance use disorders, and criminality: a difficult problem with complex solutions

Aripiprazole and Acute Extrapyramidal Symptoms in Children and Adolescents: A Meta-Analysis

The Importance of Reverse Translation for Preclinical Off-Target Mitigation: Quantification and Mitigation of Biases in the FDA Adverse Event Reporting System

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