Psychoactive drug development, authorization, and introduction to the market: The case of methylphenidate
Keywords:Psychoactive drugs, registration process, marketing authorisation, statistical significance, clinical relevance, methylphenidate, attention deficit hyperactivity disorder, nocebo
AbstractFollowing the thalidomide (Softenon) disaster in the 1960s, the registration process for new drugs became more rigorous. Under the stricter regulations, manufacturers of new drugs are required to fulfil many regulations and conduct various studies before a drug can be approved. Methylphenidate for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents was available on the market before the creation of new regulatory authorities. This means that these authorities have not published the balance of efficacy and side effects of methylphenidate. This is an undesirable situation as methylphenidate is an amphetamine, the long-term effects of which are unknown. Although methylphenidate reduces ADHD-related behaviours in the short term, it has not been shown to demonstrate clinically relevant effects in reducing impairment. Independent researchers have not been able to show any long-term efficacy of methylphenidate in children and adolescents. The European Medicines Agency (EMA) rejected the marketing authorisation of methylphenidate for adults in 2010. The drug was approved in Germany; without the conducting of new studies, this drug was approved by the EMA through a mutual recognition procedure. Consequently, methylphenidate is now available in the whole European Union. Cochrane researchers have rejected a systematic review on this drug in adults with ADHD due to the very low quality of the available clinical trials. There is an urgent need for well-conducted long-term trials, free of bias, to assess the harms and benefits of methylphenidate in adult ADHD. In addition, the rules for granting a marketing authorisation of new drugs should ensure that clinical relevance rather than statistically significant effects becomes the most important endpoint of clinical trials investigating the efficacy of drugs.