The European medical agencies have disapproved the ADHD drug Concerta for adults. The well selected short-term clinical trials did not hold: No certain positive effects; clear evidence that Concerta can cause anxiety and agitated conditions in adults; evidence that Concerta can cause aggression. Concerta may now only be used for adults, who before the age of 18 have had “a clear benefit from treatment” with “acceptable tolerability”; Concerta CANNOT be prescribed to other adults.
The adult market for ADHD has in pharmaceutical companies' marketing research material been described as twice the child market, but largely “untapped”, it has been seen as a future ”attractive niche,” as the area of ”greatest commercial potential.” (Commercial And Pipeline Insight: ADHD - Immature Adult Market Continues To Offer Greatest Commercial Potential).
The pharmaceutical company Johnson & Johnson would be first on the “adult market” in Europe, with its stimulant drug Concerta (methylphenidate).
26 February 2010 the Company submitted its application to get Concerta approved for adults in Europe (“Addition of a New Therapeutic Indication”: ADHD in adults) to the UK Medicines and Healthcare products Regulatory Agency, MHRA, with copies to all other medical agencies in Europe. The submission was so secret that the Swedish Medical Products Agency (MPA) could not even tell if any application had been submitted or not. Courts in Sweden, however, ordered the MPA to release parts of the application.
Now, the various regulatory authorities should comment on the application and the submitted studies, and so Concerta would get an approval. It is not difficult, despite ideas to the contrary, to meet the requirements for obtaining approval of a psychiatric drug. All what was needed at this stage was for Johnson & Johnson to show that Concerta short-term was more “effective” than placebo (sugar pill) in a few well-chosen areas, and that the drug didn’t have too many serious short-term harmful effects. And by ”short” is meant just a few weeks.
But this did not happen.
Johnson & Johnson has been forced to withdraw its application for an ”adult indication” of Concerta. The Company selected and submitted studies, which would show the short-term efficacy of Concerta over placebo, did not hold. The regulatory authorities could not approve Concerta for adults.
In only ONE of the submitted studies had Concerta better short-term (5 weeks) effect on the predetermined criteria than placebo, in the other two trials could not even short-term (up to 13 weeks), a statistically significant efficacy be established for Concerta versus placebo ("a statistically significant difference in the proportion of patients meeting predefined response criteria was not demonstrated between CONCERTA XL and placebo").
It emerged in these studies, clear evidence that Concerta could CAUSE anxiety and agitated conditions in adults (”Evidence for the risk of new-onset anxiety, tension and agitation”).
However Johnson & Johnson explained - quite logically - that it was not necessary to issue a warning about this as it was not relevant to prescribe Concerta for adults . The UK MHRA explained the company's position as follows: ”The Company no longer seeks an extension of the indication to include adults with ADHD”. The company further explained that ”those patients with ADHD who would be considered for continuation of treatment into adulthood must have previously been treated with methylphenidate and continue to show adequate response and acceptable tolerability”.
Note that the UK Regulator uses the word MUST.
Note that the regulatory authorities and the manufacturer, Johnson & Johnson, are in complete agreement that it is not relevant to start treating persons over 18 years with Concerta - ”those patients with ADHD who would be considered for continuation of treatment into adulthood must have previously been treated with methylphenidate and continue to show adequate response and acceptable tolerability”.
The same thing happened with the clear signs of aggression. The Dutch Medical Agency (CBG) wanted to issue special warnings about the risks with aggression in adults who took Concerta, because aggression ”might be having different implications for adults than for children”. But Johnson & Johnson disagreed – it was after all not an issue to start treatment of adults with Concerta.
In summary: Psychiatrists in Europe cannot any longer initiate treatment of adults with Concerta. The Company has withdrawn its application - the submitted scientific studies did not hold. The studies showed clear evidence that Concerta can cause anxiety and agitated conditions in adults; evidence that Concerta can cause aggression in adults.
The Company has clearly stated that no warnings about these harmful effects will be issued, as treatment with Concerta is NOT to be initiated in adults. The UK MHRA has stated that the Company in its yearly report (up to October 2011) must show that the prescription level of Concerta in Europe is not increasing any more (“The usage in adults may not increase in this time period.”)
All this can be read in the not published document Final Variation Assessment Report for Concerta XL from the UK Regulator MHRA:
http://jannel.se/FVAR.Concerta260511.pdf The question is now if adults in the US are fully warned that Concerta can CAUSE anxiety, agitation and aggression. The question is also how FDA, with the data that has now emerged, could approve Concerta for adults.
Janne Larsson
Reporter – investigating psychiatry
