Review Reports - Does Methylphenidate Work in Children and Adolescents with Attention Deficit Hyperactivity Disorder?

Round 1

Reviewer 1 Report

Overall a well developed paper that addresses a very significant problem. The following are only minor points that can be resolved with the copy editor.

Line 42 State what is Methylphenidate. For example: Methylphenidate is a central nervous system stimulant drug, that has for more than 60 years been considered the first-line pharmacological treatment for children and adolescents with ADHD.

Unsure who are the “We” in line 46 ? Consider, Storebø and colleagues ……then put the 6 and 7 reference at the end of the sentence. Also the next sentence is confusing, consider: In was noted in the Storebø reviews that there seems to be, methodological flaws in many of the 185 studies…..

Again avoid the We in the next sentence line 50. Given that there is a different set and order of authors in this paper to the 6 and 7 refenced papers "We" should not be avoided.

In line 72, Is the "We" i now the authors of this paper? Do try to avoid this We across the paper. Be specific as there are a number of different reviews being referenced in the paper.

This sentence, line 107 is unfinished or needs to be reworked as it does not make sense with the are at the end. “The generalisability of the results however, may be limited as data from only one study contributed to most of the analyses are .”

Who are the authors in this sentence line 121. Furthermore, the authors assessed all the indirect comparisons at low to very low quality….? Is it Cortese et al. (2018) if so state that, if it the authors of this paper state that?

Incorrect verb tense in this sentence line 170 needs to be suggested rather than suggest. They advised that this risk be considered against the benefits of medication and suggest regular monitoring of heart rate and blood pressure (26).

Also incorrect verb tense, They argue should be They argued line 220

The authors note at the end of their paper that schools need to do more to accommodate students who find sitting still for long periods of time difficult. The authors may like to extend this point and the following article may be relevant https://doi.org/10.1177/1087054715625301

Author Response

Dear Reviewer 1,

Thank you for your valuable feedback. Please find our reply to any raised points inserted in blue type below.

Regards,

Ole Jakob Storebø on behalf of all authors

Reviewer 1

Overall a well developed paper that addresses a very significant problem. The following are only minor points that can be resolved with the copy editor.

Thank you very much.

Line 42 State what is Methylphenidate. For example: Methylphenidate is a central nervous system stimulant drug, that has for more than 60 years been considered the first-line pharmacological treatment for children and adolescents with ADHD.

We have added the information that methylphenidate is a central nervous stimulant by changing the text to the following:

“The disorder is diagnosed in increasing proportions of children and adolescents, which brings focus to the central nervous stimulant methylphenidate. This drug has been considered the first-line pharmacological treatment for children and adolescents with ADHD for more than 60 years (5). “

Unsure who are the “We” in line 46 ? Consider, Storebø and colleagues ……then put the 6 and 7 reference at the end of the sentence. Also the next sentence is confusing, consider: In was noted in the Storebø reviews that there seems to be, methodological flaws in many of the 185 studies…..

We have tried to clarify that we are talking about the Cochrane review Storebø et al 2015 and edited the text as follows:

“The Cochrane review by Storebø et al. investigated the beneficial and harmful effects of methylphenidate as treatment for children and adolescents with ADHD (6, 7). Storebø and colleagues included 185 randomised clinical trials and found small potential beneficial effects of methylphenidate versus placebo or no-intervention. They noted that there seems to be methodological flaws, such as lack of blinding and outcome reporting bias in the included trials, prevented a clear estimation on the magnitude of intervention effects (6, 7)”

Again avoid the We in the next sentence line 50. Given that there is a different set and order of authors in this paper to the 6 and 7 refenced papers "We" should not be avoided.

We see your point that “we” is confusing and should be avoided. We have revised the sentence in line 50 as follows:

“Storebø and colleagues found that methylphenidate may improve teacher‐rated ADHD symptoms (standardised mean difference (SMD) ‐0.77, 95% confidence interval (CI) ‐0.90 to ‐0.64; 19 trials, 1698 participants. The evidence was rated as very low‐quality evidence due to risk of bias and heterogeneity”.

In line 72, Is the "We" i now the authors of this paper? Do try to avoid this We across the paper. Be specific as there are a number of different reviews being referenced in the paper.

We have specified that we are referring to us, the authors of this this paper with the following edit:

“This viewpoint provides an overview of the evidence since the Cochrane review by Storebø and colleagues in 2015 (6, 7).”

Throughout the text, we have now made sure that anytime “we” is mentioned it is referring to this paper only to avoid misunderstandings

This sentence, line 107 is unfinished or needs to be reworked as it does not make sense with the are at the end. “The generalisability of the results however, may be limited as data from only one study contributed to most of the analyses are .”

We have revised the sentence as follows:

“The generalisability of the results however, may be limited as data from only one study contributed to most of the analyses”.

Who are the authors in this sentence line 121. Furthermore, the authors assessed all the indirect comparisons at low to very low quality….? Is it Cortese et al. (2018) if so state that, if it the authors of this paper state that?

We have clarified that we are referring to Catala-Lopez et al (2017) by the following revision:

“Catala-Lopez and colleagues deemed methylphenidate an efficient treatment on ADHD symptoms especially when combined with behavioural therapy. This conclusion was made with low to very low certainty in the evidence (21).”

Incorrect verb tense in this sentence line 170 needs to be suggested rather than suggest. They advised that this risk be considered against the benefits of medication and suggest regular monitoring of heart rate and blood pressure (26).

Corrected to: “They advised that this risk be considered against the benefits of medication and suggested regular monitoring of heart rate and blood pressure (26).”

Also incorrect verb tense, They argue should be They argued line 220

Corrected to: “They argued that some children with ADHD struggle with the expectations in school to do sedentary work and concentrate for hours.”

The authors note at the end of their paper that schools need to do more to accommodate students who find sitting still for long periods of time difficult. The authors may like to extend this point and the following article may be relevant https://doi.org/10.1177/1087054715625301

Thank you very much for drawing our attention to this publication, we have incorporated it into our text and extended our point as follows:

“This environment may, for some children be the reason for their inattention and hyperactivity symptoms. This may be accommodated by a change in the environment, e.g. more physical activity in school (60) and Mindfulness-Based Therapies.”

Author Response File: Author Response.docx

Reviewer 2 Report

The manuscript entitled “Does methylphenidate work in children and adolescents with Attention Deficit Hyperactivity Disorder?” has been carried out to assess the balance of benefices and harms of methylphenidate in kids and adolescents. First it all, I would like to say that studies such as these ones are quite necessary, especially in regard to drugs administered to youth. Authors have clearly shown pros and cons of methylphenidate use, and the necessity of assessing short and long effects in population. Regarding harm effects, authors focused on physical problems and this reviewer was also expecting to know possible collateral cognitive effects after methylphenidate withdrawal. In regard to formal structure, I would like to remark that the manuscript is well organized and written. In addition, Pereira et al study is supporting by an amount of previous paper focused on this issue. They should correct some typo in the text.

Author Response

Dear Reviewer 2,

Thank you for your valuable feedback. Please find our reply to any raised points inserted in blue type below.

Regards,

Ole Jakob Storebø on behalf of all authors

Reviewer 2

Thank you very much, we agree.

Regarding harm effects, authors focused on physical problems and this reviewer was also expecting to know possible collateral cognitive effects after methylphenidate withdrawal.

Thank you for drawing our attention to this; it is an excellent point, which we agree, is very important and underreported. We have added a section on this on page 4:

“None of the included reviews of good quality from our search mentioned the effects of withdrawal symptoms. It is important however, to investigate collateral cognitive and emotional withdrawal effects such as s depression, poor concentration, agitation, irritability, and anxiety.

Consequently, when comparing benefits and harms it seems there are substantial risks of harms, which may have been overlooked in previous publications (55). Against these risks, one has to evaluate the benefits”

In regard to formal structure, I would like to remark that the manuscript is well organized and written. In addition, Pereira et al study is supporting by an amount of previous paper focused on this issue.

Thank you very much.

They should correct some typo in the text.

We have proofread the text and corrected any typos found.