Comparative short term efficacy and tolerability of methylphenidate and atomoxetine in attention deficit hyperactivity disorder

Garg, Jasmin; Arun, Priti; Chavan, BS

doi:10.1007/s13312-014-0445-5

Cited by 23 publications

(19 citation statements)

References 17 publications

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“…Figure 3 shows the results of the four studies that compared the post- vs. pre-treatment HR between children and adolescents taking methylphenidate and atomoxetine [13,43,44,45]. Children and adolescents treated with atomoxetine had a more significant increase in post- vs. pre-treatment HR than those treated with methylphenidate (pooled SMD with random-effects model: 0.86, 95% CI: 0.11–1.62, z = 2.24, p = 0.025).…”

Section: Resultsmentioning

confidence: 99%

The Effect of Methylphenidate and Atomoxetine on Heart Rate and Systolic Blood Pressure in Young People and Adults with Attention-Deficit Hyperactivity Disorder (ADHD): Systematic Review, Meta-Analysis, and Meta-Regression

Liang

Lim

Tam

et al. 2018

IJERPH

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Objectives: This meta-analysis aims to study the effects of atomoxetine and methylphenidate on heart rate (HR), systolic blood pressure (SBP), and a number of adverse cardiac events on patients receiving treatment for attention-deficit hyperactive disorder (ADHD) in comparison to placebo and between atomoxetine and methylphenidate. Methods: We searched the following databases: PubMed, EMBASE, and ScienceDirect. Meta-analysis was performed on studies that examined the relationships between methylphenidate or atomoxetine and HR, SBP, as well as a number of adverse cardiac events. These studies were either placebo-controlled or comparison studies between methylphenidate and atomoxetine. Meta-regression identified patient- and treatment-related factors that may contribute to heterogeneity. Results: Twenty-two studies were included and the total number of participants was 46,107. Children/adolescents and adults treated with methylphenidate had more significant increases in post- vs. pre-treatment HR (p < 0.001) and SBP (p < 0.001) than those treated by placebo. Children and adolescents treated with atomoxetine had more significant increases post- vs. pre-treatment HR (p = 0.025) and SBP (p < 0.001) than those treated with methylphenidate. Meta-regression revealed mean age of participants, mean dose, and duration of atomoxetine and methylphenidate as significant moderators that explained heterogeneity. There were no differences in the number of adverse cardiac events between participants with methylphenidate treatment and placebo or atomoxetine. Conclusions: Children/adolescents and adults treated with methylphenidate resulted in significant increases in post- vs. pre-treatment HR and SBP as compared to placebo. Similarly, children and adolescents treated with atomoxetine had significant increases in post- vs. pre-treatment HR and SBP than those treated with methylphenidate. These findings have potential implications for continuous monitoring of HR and SBP throughout the course of treatment although the risk for adverse cardiac events were insignificant.

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Section: Resultsmentioning

confidence: 99%

The Effect of Methylphenidate and Atomoxetine on Heart Rate and Systolic Blood Pressure in Young People and Adults with Attention-Deficit Hyperactivity Disorder (ADHD): Systematic Review, Meta-Analysis, and Meta-Regression

Liang

Lim

Tam

et al. 2018

IJERPH

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“…Clonidine immediate release and guanfacine immediate release could not be included in the network due to lack of data. Trials: Biederman [ 28 ]; Biederman [ 29 ]; Block [ 32 ]; Coghill [ 33 ]; Dittmann [ 34 ]; Dittmann [ 35 ]; Findling [ 36 ]; Findling [ 37 ]; Garg [ 38 ]; Gau [ 39 ]; Hervas [ 41 ]; Kelsey [ 42 ]; Kollins [ 43 ]; López [ 44 ]; Martenyi [ 45 ]; Montoya [ 48 ]; Newcorn [ 49 ]; Newcorn [ 50 ]; Palumbo [ 51 ]; Sallee [ 30 ]; Shang [ 52 ]; Spencer [ 31 ]; Steele [ 53 ]; Su [ 54 ]; Takahashi [ 55 ]; Wang [ 56 ]; Wehmeier [ 57 ]; Weiss [ 58 ]; Wigal [ 59 ]; Wilens [ 60 ]; Wilens [ 61 ]; Wolraich [ 62 ]. ATX atomoxetine; GXR guanfacine extended release, LDX lisdexamfetamine dimesylate, MPH-ER/OROS methylphenidate extended release/osmotic-release oral system, MPH-IR methylphenidate immediate release …”

Section: Resultsmentioning

confidence: 99%

Comparative efficacy and safety of attention-deficit/hyperactivity disorder pharmacotherapies, including guanfacine extended release: a mixed treatment comparison

Joseph¹,

Ayyagari

Xie

et al. 2017

Eur Child Adolesc Psychiatry

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This study compared the clinical efficacy and safety of attention-deficit/hyperactivity disorder (ADHD) pharmacotherapy in children and adolescents 6–17 years of age. A systematic literature review was conducted to identify randomized controlled trials (RCTs) of pharmacologic monotherapies among children and adolescents with ADHD. A Bayesian network meta-analysis was conducted to compare change in symptoms using the ADHD Rating Scale Version IV (ADHD-RS-IV), Clinical Global Impression–Improvement (CGI-I) response, all-cause discontinuation, and adverse event-related discontinuation. Thirty-six RCTs were included in the analysis. The mean (95% credible interval [CrI]) ADHD-RS-IV total score change from baseline (active minus placebo) was −14.98 (−17.14, −12.80) for lisdexamfetamine dimesylate (LDX), −9.33 (−11.63, −7.04) for methylphenidate (MPH) extended release, −8.68 (−10.63, −6.72) for guanfacine extended release (GXR), and −6.88 (−8.22, −5.49) for atomoxetine (ATX); data were unavailable for MPH immediate release. The relative risk (95% CrI) for CGI-I response (active versus placebo) was 2.56 (2.21, 2.91) for LDX, 2.13 (1.70, 2.54) for MPH extended release, 1.94 (1.59, 2.29) for GXR, 1.77 (1.31, 2.26) for ATX, and 1.62 (1.05, 2.17) for MPH immediate release. Among non-stimulant pharmacotherapies, GXR was more effective than ATX when comparing ADHD-RS-IV total score change (with a posterior probability of 93.91%) and CGI-I response (posterior probability 76.13%). This study found that LDX had greater efficacy than GXR, ATX, and MPH in the treatment of children and adolescents with ADHD. GXR had a high posterior probability of being more efficacious than ATX, although their CrIs overlapped.Electronic supplementary materialThe online version of this article (doi:10.1007/s00787-017-0962-6) contains supplementary material, which is available to authorized users.

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“…Reductions in body weight have also been detected in children and adolescents treated with lisdexamfetamine [74] and methylphenidate [21,75,86] in some comparative studies using atomoxetine. In a 9-week randomized, double-blind study, reductions in body weight were greater with lisdexamfetamine (mean [SD] -1.30 kg [1.81]) than with atomoxetine (-0.15 kg [1.43]), and a greater proportion of patients had a C7 % reduction in weight from baseline with lisdexamfetamine (26.8 %; N = 34/127) than with atomoxetine (4.5 %; N = 6/132) [74].…”

Section: Findings In the Predefinedmentioning

confidence: 94%

“…However, reductions in body weight are not universally reported: the authors of some short-term studies (B14 weeks) report either no change or a small increase in mean weight [55,69,75,80,81] and/or describe weight changes as not ''clinically significant'', not ''clinically meaningful'', or ''small'' [55,67,79,80,86].…”

Section: Findings In the Predefinedmentioning

confidence: 99%

“…Two 8-week studies comparing atomoxetine with methylphenidate appear to report contrasting data about weight loss. In an 8-week, randomized, open-label study of 69 children and adolescents, there was a significant reduction in weight from baseline with methylphenidate (mean [SD] -0.57 kg [0.78]; p = 0.001), whereas no significant reduction was detected with atomoxetine, although the weight data were not reported for atomoxetine [75]. Conversely, in an 8-week double-blind RCT, the proportions of patients with C3.5 % weight loss were 49.4 % (N = 80/162) with atomoxetine versus 25.6 % (N = 42/164) with methylphenidate [86].…”

Section: Findings In the Predefinedmentioning

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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Comparative short term efficacy and tolerability of methylphenidate and atomoxetine in attention deficit hyperactivity disorder

Abstract: Methylphenidate and atomoxetine are efficacious in Indian children with ADHD at lesser doses than previously used. Their efficacy and tolerability are comparable. TRIAL REGISTRATION NO.: CTRI/2011/08/001981.

Cited by 23 publications

References 17 publications

The Effect of Methylphenidate and Atomoxetine on Heart Rate and Systolic Blood Pressure in Young People and Adults with Attention-Deficit Hyperactivity Disorder (ADHD): Systematic Review, Meta-Analysis, and Meta-Regression

The Effect of Methylphenidate and Atomoxetine on Heart Rate and Systolic Blood Pressure in Young People and Adults with Attention-Deficit Hyperactivity Disorder (ADHD): Systematic Review, Meta-Analysis, and Meta-Regression

Comparative efficacy and safety of attention-deficit/hyperactivity disorder pharmacotherapies, including guanfacine extended release: a mixed treatment comparison

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

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