The Jury Is In On Storebø & Simonsen – You’re done!
After 4 years of bickering and with no useful results, Storebø OJ. and Simonsen E. et al. have just wasted God knows how much of our scarce research funds on … what!? … Nothing! … We call for a scientific enquiry into their agenda!
In 2015, Storebø et al. published a meta-analysis, a so-called Cochrane System Review, where they argued that the current evidence on the safety and efficacy of Methylphenidate for treatment of ADHD, was of ‘very low quality’ and therefore they claimed, that the current consensus in all major guideline (NICE etc.) was not based on tangible evidence, and was most likely influenced by Big Pharma, since they had sponsored some of the studies. They claimed that out of 260 analyzed studies, only 19 of them could be deemed as ‘not being biased’, according to their own definitions (the GRADE method from Cochrane Institute). Thereby they discredited 50 years of research in Methylphenidate.
At the same time, Storebø et al. claimed that the levels of serious, and non-serious adverse events (side-effects) was not being truthfully reported, since the study designs used, was not up to their scientific standards. Since then, Storebø et al., have tried to provide proof of their claims, but have continually failed to do so, when challenged by the leading researchers in the filed of ADHD research, including Dr. Russell A. Barkley, Ph.D., Dr. Dr. Tobias Banascheski, Cortese S., Coghill D., Buitelaar J. and others.
Another point of critic, was not using the NOCEBO method in the analyzed studies. NOCEBO is a pill that will cause ‘normal’ persons to begin exhibit ADHD-like symptoms, and then these can be given Methylphenidate, so that the researcher can adequately asses the efficacy of Methylphenidate for treatment of ADHD.
Both Barkley and Banaschewski pointed out, that such a NOCEBO did not exist, and that if it did, it would be in violation with both ethical standards and human rights law, to induce healthy subjects with ADHD-like symptoms.
Dr. Barkley went as far as to describe their demands to be […] the requirement that studies must use a “nocebo” shows that the authors are not aware that such studies would also not be permitted by IRBs not only for the reasons given above but also because you cannot inflict suffering and harm on people, via inducing side effects, when there is no offsetting benefit to doing so. I am not aware that any such nocebo exists that can specifically create MPH side effects in the equivalent proportion of people and to the equivalent degree as MPH. And even if such a currently fantasy drug existed no IRB here would permit its use. So the authors are asking for the impossible while judging the existing database against a fantasy. That is not a very fair assessment of the prevailing evidence even if they are technically correct about the short term duration of most trials, done mostly of necessity.[…]
Over the past 4 years, Storebø OJ. and Simonsen E. have tried to provide evidence to Methylphenidate being harmful and without efficacy, but they have not only failed miserably, caused unnecessary panic for clinicians, policy-makers and patients, been overly biased in their press-releases by always spinning their results in the least beneficial way for the current evidence, while overstating the importance of their own findings.
Simultaneously, they have tried to link ADHD to;
- tried to make ADHD a ‘pre-stage of Borderline’ (and failed),
- tried to link gastro-internal problems to the use of Methylphenidate (and failed)
- tried to link psychotic episodes to the use of Methylphenidate (and failed)
- tried to discredit every major scientist within the ADHD research community by implying that ‘they most likely were bought and paid for, by Big Pharma) (and failed to prove anything).
Lastly they have now concluded; ‘ … methylphenidate for children and adolescents with ADHD seem to offer the same advantages and pose similar problems…’ in their 2019 study.
Ironically enough, Storebø OJ.’s own Ph.D. Thesis on Social Skills Training for children with ADHD, concludes: […] Further studies of efficacy of other psychosocial interventions are needed, i.e., investigations regarding a possible link between attachment style and ADHD and intervention programmes that specifically addresses these issues. There is little evidence to support or refute social skills training for children with ADHD at present. There might be an association between ADHD and attachment, suggesting that social skills treatment must also address the attachment problems to be effective. Therefore, it is possible that a treatment addressing the more profound aspects of children‟s personality would be more effective for the treatment of ADHD core symptoms and related social skill problems.[…] Storebø OJ. (2012)
Simonsen E. is right on the same page as Storebø OJ., just listen to what he writes about ADHD in the official curriculum for basic psychiatry in Denmark, in 2017: […] ADHD is another diagnosis that has gained increasing use in recent years and which in some cases is likely to be used in conjunction with conditions which would not previously be characterized as abnormal or morbid, eg difficulty in concentrating, restlessness, motor unrest and impulsivity in children. The need to explain, diagnose and treat anxiety and difficulty in concentration, which is not so uncommon in children, may have led to over-diagnosis and treatment of ADHD. The risk of having an ADHD diagnosis is greatly increased for the youngest children in the class, which is explained by the fact that they are more immature and therefore uneasy than their older classmates. Studies show that the youngest boy in the class has about 30% greater risk of having an ADHD diagnosis than the other children. Some have pointed to greater demands on modern man in the Western world for control and performance, so there is less tolerance for deviations and suboptimal function. In the debate on the diagnosed life lies a criticism of the cultural demands and expectations, where “the perfect has become the new normal” and of the treatment system, where even minor deviations become ill, and it has also been pointed out that there are strong economic interests Diagnosis of new conditions, because a diagnosis often causes indication of medical treatment, for example, the consumption of ADHD drugs has increased dramatically in recent years, thus the pharmaceutical companies have commercial interests in the growth of new diagnoses. ” […] Simonsen E. & Møhl B., Basic book in Psychiatry, 2nd edition, p. 51 (2017)
In my opinion, it would be pertinent for the scientific community in Denmark to put Storebø OJ. and Simonsen E. through a scientific enquiry on the basis of ‘scientific negligence’ on the basis of trying to distort the ‘evidence’ of their findings, ‘bending’ the results to fit their agenda, deliberately misinterpret the factual, scientific evidence of their own data, while going to the media with a clear intention of creating a ‘false flag event’ on ADHD medication, so to further they own personal goals, not those of we, the patients.
And Storebø OJ., I can see that you have made yet another, pretty significant error, this time on your Cochrane Institute website, where you are stating that ADHD is not a neurodevelopmental disorders, but is placed under the category Psychosocial Problems, while Autism Spectrum Disorder is correctly placed under the category ‘Developmental Problems’, this is, by far, the most clear evidence of Cochrane’s bias against ADHD, and it is not what I expected to find, in 2019, from an institution claiming to these values; ‘Trusted evidence. Informed decisions. Better health.’
The Jury Is In On Storebø & Simonsen – You’re done! After 4 years of bickering and with no useful results, Storebø OJ. and Simonsen E. et al. have just wasted God knows how much of our scarce research funds on … what!? … Nothing! … We call for a scientific enquiry into their agenda!Peter ‘ADDspeaker’ Vang (2019)
/Peter ‘ADDspeaker’ Vang
Founder & Citizen Scientist
ADDspeaker.org is a grassroots organization, that provides unbiased, scientific, and evidence-based knowledge to regular people, with and without ADHD, with the purpose of providing insight to the diagnosis and treatment of ADHD, by collaborating with scientists from all over the world, so as to be able to share their findings with non-scientifically trained people, for the benefit of their everyday management of, and understanding of, ADHD.
We also participate in the public debate on the topic of ADHD, to influence the public understanding, as well as provide support for lawmakers in creating guidelines, based on the latest scientific evidence.
ADDspeaker.org is not affiliated with ANY financial, religious, pharmaceutical, or political institutions, and we are run 100% on not-for-profit principles, and without any personal gains as motive.
Our values are: Insight, Knowledge, Recognition, Respect … and Caring …
For more information: http://addspeaker.org
[…] This study mostly found no signs of period effects or carry-over effects in crossover trials assessing methylphenidate for children and adolescents with ADHD. Accordingly, crossover trials and parallel trials on methylphenidate for children and adolescents with ADHD seem to offer the same advantages and pose similar problems as described for these two designs in other therapeutic areas. Despite the insignificant results, crossover trial suitability for methylphenidate trials should still be questioned.[…]
Krogh, H. B., Storebø, O. J., Faltinsen, E., Todorovac, A., Ydedahl-Jensen, E., Magnusson, F. L., … Simonsen, E. (2019). Methodological advantages and disadvantages of parallel and crossover randomised clinical trials on methylphenidate for attention deficit hyperactivity disorder: a systematic review and meta-analyses. BMJ Open, 9(3), e026478. doi:10.1136/bmjopen-2018-026478
[…] About 1 in 100 patients treated with methylphenidate seemed to suffer a serious adverse event. Withdrawal from methylphenidate due to serious adverse events occurred in about 1.2 out of 100 patients treated with methylphenidate. Withdrawal from methylphenidate due to any adverse events occurred in about 7.3 out of 100 patients treated with methylphenidate.[…]
[…] Because of sparse data and low quality of evidence, we cannot confirm or refute whether methylphenidate increases the risk of psychotic symptoms in children and adolescents with ADHD. This possible adverse event may affect 1.1% to 2.5%, and physicians, patients and caregivers should be aware of this to ensure proper treatment in case of occurrence during methylphenidate treatment[…]
Ramstad, E., Storebø, O. J., Gerner, T., Krogh, H. B., Holmskov, M., Magnusson, F. L., … Simonsen, E. (2018). Hallucinations and other psychotic symptoms in response to methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder: a Cochrane systematic review with meta-analysis and trial sequential analysis#. Scandinavian Journal of Child and Adolescent Psychiatry and Psychology, 6(1), 52–71.
[…] In our network meta-analysis, we summarised the best available evidence about efficacy and accept-ability of ADHD medications. In the protocol, we planned analyses of clinical outcomes at different time-points (acute and long term) but, unfortunately, there are not enough randomised controlled trials in the field. More long-term data and higher quality studies are urgently needed. We totally agree with John Warren that it is important to consider reliable information also about safety and harms when choosing a pharmacological treatment for ADHD (of course, this applies to any intervention in any disorder in any field of medicine).[…]
Cipriani, A., Adamo, N., Giovane, C. Del, Coghill, D., Banaschewski, T., Hollis, C., … Cortese, S. (2018). Unbalanced risk-benefit analysis of ADHD drugs – Authors’ reply. The Lancet Psychiatry, 5(11), 871–873. DOI: https://doi.org/10.1016/s2215-0366(18)30396-1
[…] Although we appreciate the work by Cortese and colleagues, we hope that future reviews will address the outlined issues and move from group-level data to individual participant data to explore patient-related variables further. We strongly encourage longer-lasting and rigorously designed randomised clinical trials on medications for patients with ADHD (incorporating active placebos with so-called nocebo components), to improve the current evidence base.[…]
Faltinsen, E. G., Gluud, C., Simonsen, E., Zwi, M., & Storebø, O. J. (2018). Unbalanced risk-benefit analysis of ADHD drugs. The Lancet Psychiatry, 5(11), 870. doi: 10.1016/s2215-0366(18)30334-1
[…] Our findings represent the most comprehensive available evidence base to inform patients, families, clinicians, guideline developers, and policymakers on the choice of ADHD medications across age groups. Taking into account both efficacy and safety, evidence from this meta-analysis supports methylphenidate in children and adolescents, and amphetamines in adults, as preferred first-choice medications for the short-term treatment of ADHD. New research should be funded urgently to assess long-term effects of these drugs. […]
Cortese, S., Adamo, N., Del Giovane, C., Mohr-Jensen, C., Hayes, A. J., Carucci, S., … Cipriani, A. (2018). Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. The Lancet Psychiatry. doi:10.1016/s2215-0366(18)30269-4
[…] Industry sponsorship may also bias the assessment of intervention effects and the results of network meta-analyses, including their ranking estimates. For instance, meta-analyses on antidepressant drugs are far less likely to report negative statements, if review authors have conflicts of interest. Pharmaceutical companies are regularly involved in performing network meta-analyses, and in one survey, 19 contracting companies reported that they had performed a total of 476 network meta-analyses, only to publish 102 of them (21%). Research on the impact of industry sponsorship and publication bias on treatment rankings in network meta-analyses is urgently needed.[…]
Faltinsen, E. G., Storebø, O. J., Jakobsen, J. C., Boesen, K., Lange, T., & Gluud, C. (2018). Network meta-analysis: the highest level of medical evidence? BMJ Evidence-Based Medicine, 23(2), 56–59. doi: 10.1136/bmjebm-2017-110887
[…]The existing studies on benefits and harms of methylphenidate for ADHD have substantial methodological flaws.[…]
Storebø, O. J., Faltinsen, E., Zwi, M., Simonsen, E., & Gluud, C. (2018). The Jury Is Still Out on the Benefits and Harms of Methylphenidate for Children and Adolescents With Attention-Deficit/Hyperactivity Disorder. Clinical Pharmacology & Therapeutics. doi:10.1002/cpt.1149
[…]Our findings suggest that methylphenidate may be associated with a number of serious adverse events as well as a large number of non-serious adverse events in children and adolescents, which often lead to withdrawal of methylphenidate. Our certainty in the evidence is very low, and accordingly, it is not possible to accurately estimate the actual risk of adverse events. It might be higher than reported here. Given the possible association between methylphenidate and the adverse events identified, it may be important to identify people who are most susceptible to adverse events. To do this we must undertake large-scale, high-quality RCTs, along with studies aimed at identifying responders and non-responders.[…]
Storebø, O. J., Pedersen, N., Ramstad, E., Kielsholm, M. L., Nielsen, S. S., Krogh, H. B., … Gluud, C. (2018). Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents – assessment of adverse events in non-randomised studies. Cochrane Database of Systematic Reviews. doi: 10.1002/14651858.cd012069.pub2
[…]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.[…]
Holmskov, M., Storebø, O. J., Moreira-Maia, C. R., Ramstad, E., Magnusson, F. L., Krogh, H. B., … 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. doi: 10.1371/journal.pone.0178187
[…]The trial selection in our review is not flawed. The effect sizes are not too small. We followed a sound methodology for the assessment of bias, and our conclusions are not misleading.[…]
StorebØ, O. J., Zwi, M., Moreira-Maia, C. R., Skoog, M., Camilla, G., Gillies, D., … Gluud, C. (2016). Response to “trust, but verify” by banaschewski et al. Zeitschrift Fur Kinder- Und Jugendpsychiatrie Und Psychotherapie, 44(5), 334–335. https://doi.org/10.1024/1422-4917/a000472
[…]Let us conclude that the Cochrane review by Storebo et al. (2015) is indeed flawed in terms of study selection and risk of bias assessment. We think that the clinical interpretation of the flawed analysis should not be admissible and lacks careful consideration.[…]
Banaschewski, T., Gerlach, M., Becker, K., Holtmann, M., Döpfner, M., & Romanos, M. (2016). Trust, but verify. The errors and misinterpretations in the Cochrane analysis by O.J. Storebo and colleagues on the efficacy and safety of methylphenidate for the treatment of children and adolescents with ADHD. Zeitschrift Fur Kinder- Und Jugendpsychiatrie Und Psychotherapie, 44(4), 307–314. https://doi.org/10.1024/1422-4917/a000433
[…]Overall, it can be concluded that even Cochrane works should be critically read and verified. As recently demonstrated by Guy Goodwin (2015), they are potentially misleading, for instance, if inadequate inclusion criteria are defined for studies, because dose-finding studies with too low dosages are used to assess efficacy, if studies that applied too high dosages are included to assess the frequency of ADRs, or if inappropriate criteria are applied to assess the validity of studies and available evidence is thus negated. The consequences of this become apparent in underestimated efficacy, overestimated risks, and uncertainty on the part of clinicians and patients.[…]
[…]Banaschewski and colleagues from the European Attention Deficit Hyperactivity Disorder (ADHD) guideline group make a number of critical comments regarding our systematic review on methylphenidate for children and adolescents with ADHD. In this article, we present our views, showing that our trial selection was not flawed and was undertaken with scientific justification. Similarly, our data collection and interpretation was systematic and correct. We have followed a sound methodology for assessing risk of bias and our conclusions are not misleading. We acknowledge that different researchers might make risk of bias judgments at higher or lower thresholds, but we have been consistent and transparent in applying our pre-defined and per reviewed protocol. Although we made minor errors, we demonstrate that the effects are negligible and not affecting our conclusions. We are happy to correct such errors and to engage in debate on methodological and ethical issues. In terms of clinical implications, we are advocating that clinicians, patients and their relatives should weight carefully risks and benefits of methylphenidate. Clinical experience seems to suggest that there are people who benefit from this medication. Our systematic review does, however, raise questions regarding the overall quality of the methylphenidate trials.[…]
Storebø, O. J., Zwi, M., Krogh, H. B., Moreira-Maia, C. R., Holmskov, M., Gillies, D., … Gluud, C. (2016). Evidence on methylphenidate in children and adolescents with ADHD is in fact of “very low quality.” Evidence Based Mental Health, 19(4), 100–102. doi: 10.1136/eb-2016-102499
[…]A recent Cochrane review assessed the efficacy of methylphenidate for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. Notwithstanding the moderate-to-large effect sizes for ADHD symptom reduction found in the meta-analysis, the authors concluded that the quality of the evidence is low and therefore the true magnitude of these effects remain uncertain. We identified a number of major concerns with the review, in the domains of study inclusion, approaches to quality assessment, and interpretation of data relating to serious adverse events as well as of the clinical implications of the reported effects. We also found errors in the extraction of data used to estimate the effect size of the primary outcome. Considering all the shortcomings, the conclusion in the Cochrane review that the status of the evidence is uncertain is misplaced. Professionals, parents and patients should refer to previous reviews and existing guidelines, which include methylphenidate as one of the safe and efficacious treatment strategies for ADHD.[…]
Banaschewski, T., Buitelaar, J., Chui, C. S. L., Coghill, D., Cortese, S., Simonoff, E., & Wong, I. C. K. (2016). Methylphenidate for ADHD in children and adolescents: throwing the baby out with the bathwater. Evidence Based Mental Health, 19(4), 97–99. doi: 10.1136/eb-2016-102461
[…] At the moment, the quality of the available evidence means that we cannot say for sure whether taking methylphenidate will improve the lives of children and adolescents with ADHD. Methylphenidiate is associated with a number of non-serious adverse events such as problems with sleeping and decreased appetite. Although we did not find evidence that there is an increased risk of serious adverse events, we need trials with longer follow-up to better assess the risk of serious adverse events in people who take methylphenidate over a long period of time. Given that methylphenidate is associated with adverse events, designing high quality trials is challenging. It can be easy for clinicians, researchers and participants to work out whether a child is in the experimental group (receiving methylphenidate) or in the control group (receiving the placebo). This is a serious risk of bias that can make us less confident in the results of a trial. One way to avoid this is to design trials that compare methylphenidate with a placebo that can produce similar adverse events, but which has no other active ingredient. These trials are known as ’nocebo trials’. For ethical reasons, nocebo trials should first be undertaken with adults. Only if the results suggest that methylphenidate is effective for adults, should researchers consider recruiting children to trials with this design.[…]
Storebø, O. J., Ramstad, E., Krogh, H. B., Nilausen, T. D., Skoog, M., Holmskov, M., … Gluud, C. (2015). Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). Cochrane Database of Systematic Reviews. doi: 10.1002/14651858.cd009885.pub2
[…]Further studies of efficacy of other psychosocial interventions are needed, i.e., investigations regarding a possible link between attachment style and ADHD and intervention programmes that specifically addresses these issues. There is little evidence to support or refute social skills training for children with ADHD at present. There might be an association between ADHD and attachment, suggesting that social skills treatment must also address the attachment problems to be effective. Therefore, it is possible that a treatment addressing the more profound aspects of children‟s personality would be more effective for the treatment of ADHD core symptoms and related social skill problems.[…]
Storebø, O. J. (2012). Social skills training for children with attention deficit hyperactivity disorder (Doctoral dissertation, Eget Forlag).