Evidence-based medicine is “the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients”. It means that, as a patient, you may expect your doctor to be aware of the very latest scientific progress in his/her field of expertise. It also means that, based on this knowledge, your doctor should recommend the treatment that has proven most effective and safe for patients like you.
So what if there is very little evidence to rely on? For words like ‘proven’ and ‘evidence’ to be appropriate, you will need a substantial number of patients who are indeed just like you, as well as the money, expertise, and permissions to conduct a trial. None of these are easy to come by. Your disease may be extremely rare, as is research funding these days. As one option, doctors may resort to prescribing certain drugs ‘off-label’: medicine that has been approved for one group of patients (for example, adults with schizophrenia) are then prescribed to another group (let’s say, children with severe conduct problems).
In our study of 2014, we investigated combined treatment with stimulants and atypical antipsychotics for children with attention-deficit/hyperactivity disorder, or ADHD. Stimulant treatment has extensively been investigated in this group, and is considered both effective and safe. By contrast, little is known about the effects of atypical antipsychotics, and the prescription of these drugs to children is permitted off-label. We were interested to see whether children who had received combined treatment (stimulants + antipsychotics) would show any changes in the brain, as compared to children who had been prescribed only stimulants. We found that children with ADHD showed subtle brain changes compared to children without ADHD, and that some of these changes were exaggerated in the combined treatment group.
There are two possible explanations. First, the differences may have been present before these children were ever prescribed antipsychotics. In fact, the changes might be associated with their problem behaviours, hence they could be the very reason why these children were prescribed antipsychotic treatment in the first place. The alternative explanation, much more worryingly, is that the brain changes in the combined treatment group are caused by the treatment. From our results, we can’t tell which interpretation is true. Problem is, there is no study around that can. With so little research being performed into this vulnerable group, even the slightest hint of these drugs causing potentially disadvantageous brain changes worries me.
What also worries me, is the rapidly increasing number of children being prescribed antipsychotics. A Canadian study found that the prescription rate of atypical antipsychotics had increased 18-fold between 1996 and 2011. While off-label antipsychotic treatment for children has become very much common practice, research into this treatment strategy is lagging lightyears behind. I do not think that all off-label prescriptions are bad; I’m very much in favour of ‘recycling’ and exploring possible new applications for treatments at our disposition. However, the sheer number of children now taking antipsychotics clearly allows for new, decent-powered studies into the effects of this treatment strategy. In my view, off-label prescription should always be a temporary solution. A solution that comes with the obligation to initiate research into its safety and efficacy, so that doctors will have access to the information they need to return to evidence-based medicine.