Attention-deficit/hyperactivity disorder treatment: what are the long-term cardiovascular risks?

Hammerness, Paul; Karampahtsis, Chris; Babalola, Ronke; Alexander, Mark E.

doi:10.1517/14740338.2015.1011620

Cited by 28 publications

(12 citation statements)

References 66 publications

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“…Similar elevations in heart rate and/or blood pressure have been detected with stimulants [20,21,74,107,116]. These studies include the Multimodal Treatment Study of Children with ADHD (MTA), in which heart rate was higher with stimulant medication than with behavioral therapy at 14 months (mean [SD] 84.2 [12.4] vs. 79.1 bpm [12.0]), and at 3 and 8 years, but without changes in blood pressure [116].…”

Section: Discussionmentioning

confidence: 94%

“…These increases are generally minor in healthy individuals, e.g., B7 mmHg and B10 bpm with stimulants in children and adults in the long term, although they may be higher in a sizable minority of patients [107]. When determining the clinical relevance of these cardiovascular changes, it is important to determine whether they differ from age-related norms, and whether they have the potential to lead to serious cardiovascular events.…”

Section: Introductionmentioning

confidence: 99%

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The Safety of Atomoxetine for the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Comprehensive Review of Over a Decade of Research

et al. 2016

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Atomoxetine is a noradrenergic reuptake inhibitor prescribed for attention-deficit/hyperactivity disorder (ADHD) that first gained approval in the USA in 2002 and has been authorized in 97 countries worldwide. The aim of this paper is to comprehensively review publications that addressed one or more of seven major safety topics relevant to atomoxetine treatment of children and adolescents (aged ≥6 years) diagnosed with ADHD. While the review focuses on children and adolescents, publications in which data from patients aged >18 years and from 6 to 18 years were analyzed in the same dataset were included. Using a predefined search strategy, including agreement of two reviewers when selecting papers, reduced the potential for bias. Using this process, we identified 70 eligible papers (clinical trials, epidemiological studies, and case reports) across the seven topics. We also referred to the European Summary of Product Characteristics (SPC) and US label. We found 15 papers about suicidality, three about aggression/hostility, seven about psychosis/mania, six about seizures, seven about hepatic effects, 29 about cardiovascular effects, and 28 about growth and development. The main findings (i.e., those from the largest and most well-conducted studies/analyses) are as follows. A large register-based study of pediatric and adult patients (6818 received atomoxetine) calculated a hazard ratio of 0.96 for suicide-related events during treatment with atomoxetine, and a meta-analysis of 23 placebo-controlled studies (N = 3883), published in 2014, found no completed suicides and no statistically significant association between atomoxetine and suicidality. The frequency of aggression/hostility was not statistically significantly higher with atomoxetine, e.g., experienced by 1.6 % (N = 21/1308) of atomoxetine-treated patients versus 1.1 % (N = 9/806) of placebo-treated patients in one meta-analysis. Symptoms of psychosis and mania were mainly observed in patients with comorbid bipolar disorder/depression. Based on spontaneous reports, during a 2-year period when 2.233 million adult and pediatric patients were exposed to atomoxetine, the reporting rate for seizures was 8 per 100,000 patients. In the manufacturer's database, atomoxetine was a "probable cause" of three hepatic adverse events (AEs) (all reversible hepatitis), and 133 hepatic AEs had possible confounding factors and were "possibly related" to atomoxetine, during 4 years when atomoxetine exposure had reached about 4.3 million patients. Rare cases of severe liver injury are described in the US label and European SPC; a case requiring liver transplantation is described in the US label. In a comprehensive review of a clinical trials database (N = 8417 received atomoxetine), most pediatric patients experienced modest increases in heart rate and blood pressure, and 8-12 % experienced more pronounced changes (≥20 bpm, ≥15 to 20 mmHg). However, in three long-term analyses (≥2 years), blood pressure was within age norms, and few patients discontinued due to cardiovascular AE...

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

The Safety of Atomoxetine for the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Comprehensive Review of Over a Decade of Research

et al. 2016

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“…While physicians have previously had little guidance for diagnosing and treating adult ADHD, adults have been included in recent guidelines [8, 16–19], reflecting the increasing awareness of ADHD symptoms beyond childhood. However, until recently, atomoxetine was the only drug approved for use in adults [8, 9], which reflects that long-term efficacy and safety of these drugs are insufficiently studied in adults [20–22]. Despite these considerations, use of ADHD drugs among adults has increased rapidly throughout the world [14, 23–26].…”

Section: Introductionmentioning

confidence: 99%

Use of drugs for ADHD among adults—a multinational study among 15.8 million adults in the Nordic countries

Karlstad

Zoëga

Furu

et al. 2016

Eur J Clin Pharmacol

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PurposeThe use of ADHD drugs among adults is controversial and has until recently not been approved for use in adults in most countries. The aim was to investigate use of ADHD drugs (stimulants and atomoxetine) among the entire adult population in the Nordic countries.MethodsWe conducted a multinational population-based prescription register study based on the entire adult population in the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden). All users of ADHD drugs aged 18–64 years during 2008–2012 were included, which for 2012 comprised 76,896 drug users among 15.8 million adult inhabitants.ResultsAnnual prevalence of drug use increased during the study period for both genders and all age groups. The overall prevalence increased from 2.4 to 5.3 per 1000 men and 1.8 to 4.4 per 1000 women. Incidence also increased, but to a lesser extent in the last part of the study period. Methylphenidate was used by 88 % of drug users. Treatment was discontinued within the first year by 21 % of new drug users. Among all users of ADHD drugs, 53 % of men and 64 % of women concurrently used other psychotropic drugs, most frequently antidepressants and hypnotics. Psychotropic co-medication increased with age and was more pronounced among women than men.ConclusionsUse of ADHD drug among adults more than doubled over a 5-year period, and a majority were concurrently treated with other psychotropics. Adults constitute a substantial proportion of persons treated with ADHD drugs. Thus, evidence for long-term efficacy and safety in adults is urgently needed.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-016-2125-y) contains supplementary material, which is available to authorized users.

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“…Such adverse effects, however, are typically dose-dependent. 20 Additionally, antipsychotics and mood stabilizers can often treat impulsive violence 21 and avoid the risks of stimulant-induced psychosis. 22 A further limitation of the case of Ms. B. is that there was not adequate separation of time between the initiation of clozapine and methylphenidate, specifically, methylphenidate was started 2 weeks after initiation of clozapine.…”

Section: Discussionmentioning

confidence: 99%

Stimulants for impulsive violence in schizophrenia spectrum disordered women: a case series and brief review

Skoretz

Tang

2016

CNS Spectr.

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High violence prevalence is a common concern for forensic psychiatric settings. Categorizing underlying drivers of violence has helped to direct treatment and management efforts toward psychotic, predatory, and impulsively violent psychopathology. This article describes a series of cases in which clozapine provided adequate control of psychosis in women suffering schizophrenia-spectrum disorders. Nevertheless, impulsive violence remained problematic. Add-on methylphenidate was found to be safe and effective in curbing impulsive violent behavior in this select group of patients.

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Attention-deficit/hyperactivity disorder treatment: what are the long-term cardiovascular risks?

Cited by 28 publications

References 66 publications

The Safety of Atomoxetine for the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Comprehensive Review of Over a Decade of Research

The Safety of Atomoxetine for the Treatment of Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Comprehensive Review of Over a Decade of Research

Use of drugs for ADHD among adults—a multinational study among 15.8 million adults in the Nordic countries

Stimulants for impulsive violence in schizophrenia spectrum disordered women: a case series and brief review

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