Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials

Mathilde Holmskov; Ole Jakob Storebø; Carlos R Moreira-Maia; Erica Ramstad; Frederik Løgstrup Magnusson; Helle B Krogh; Camilla Groth; Donna Gillies; Morris Zwi; Maria Skoog; Christian Gluud; Erik Simonsen

doi:10.1371/journal.pone.0178187

Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials

Mathilde Holmskov, Ole Jakob Storebø, Carlos R Moreira-Maia, Erica Ramstad, Frederik Løgstrup Magnusson, Helle B Krogh, Camilla Groth, Donna Gillies, Morris Zwi, Maria Skoog, Christian Gluud, Erik Simonsen

Department of Clinical Medicine

11 Citations (Scopus)

39 Downloads (Pure)

Abstract

OBJECTIVES: To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review.

METHODS AND FINDINGS: We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes.

CONCLUSION: Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.

Original language	English
Article number	e0178187
Journal	PloS one
Volume	12
Issue number	6
Number of pages	18
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0178187
Publication status	Published - Jun 2017

Keywords

Adolescent
Attention Deficit Disorder with Hyperactivity
Central Nervous System Stimulants
Child
Cross-Over Studies
Dose-Response Relationship, Drug
Female
Gastrointestinal Diseases
Humans
Male
Methylphenidate
Odds Ratio
Randomized Controlled Trials as Topic
Journal Article
Meta-Analysis
Review

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Holmskov, M., Storebø, O. J., Moreira-Maia, C. R., Ramstad, E., Magnusson, F. L., Krogh, H. B., Groth, C., Gillies, D., Zwi, M., Skoog, M., Gluud, C., & Simonsen, E. (2017). Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials. PloS one, 12(6), [e0178187]. https://doi.org/10.1371/journal.pone.0178187

Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder : A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials. / Holmskov, Mathilde; Storebø, Ole Jakob; Moreira-Maia, Carlos R et al.

In: PloS one, Vol. 12, No. 6, e0178187, 06.2017.

Research output: Contribution to journal › Review › peer-review

Holmskov, M, Storebø, OJ, Moreira-Maia, CR, Ramstad, E, Magnusson, FL, Krogh, HB, Groth, C, Gillies, D, Zwi, M, Skoog, M, Gluud, C & Simonsen, E 2017, 'Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials', PloS one, vol. 12, no. 6, e0178187. https://doi.org/10.1371/journal.pone.0178187

Holmskov M, Storebø OJ, Moreira-Maia CR, Ramstad E, Magnusson FL, Krogh HB et al. Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials. PloS one. 2017 Jun;12(6):e0178187. doi: 10.1371/journal.pone.0178187

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abstract = "OBJECTIVES: To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review.METHODS AND FINDINGS: We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes.CONCLUSION: Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.",

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AU - Storebø, Ole Jakob

AU - Moreira-Maia, Carlos R

AU - Ramstad, Erica

AU - Magnusson, Frederik Løgstrup

AU - Krogh, Helle B

AU - Groth, Camilla

AU - Gillies, Donna

AU - Zwi, Morris

AU - Skoog, Maria

AU - Gluud, Christian

AU - Simonsen, Erik

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N2 - OBJECTIVES: To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review.METHODS AND FINDINGS: We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes.CONCLUSION: Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.

AB - OBJECTIVES: To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review.METHODS AND FINDINGS: We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes.CONCLUSION: Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.

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KW - Odds Ratio

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KW - Journal Article

KW - Meta-Analysis

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