Experts call for more research into ADHD drug Ritali...

"The drug Ritalin should be prescribed with caution as the quality of evidence available about its benefits and risks is poor," the Mail Online reports. A review of available evidence found no high-quality evidence about both the benefits and risks.

Researchers aimed to assess the beneficial and harmful effects of the attention deficit hyperactivity disorder (ADHD) drug methylphenidate for children and adolescents – Ritalin is the most commonly known brand name.

The review identified a large number of trials including more than 12,000 children and adolescents. It found a slight improvement in symptoms of ADHD in children treated with methylphenidate compared to placebo (dummy drug) or no treatment.

There was no increase in risk of serious adverse effects, but there was also a 29% increase in non-serious side effects, such as sleep problems and decreased appetite. However, the findings were based on very low-quality evidence, so we can't be sure of these effects, and better-quality studies would be required to look at this further.

The researchers conclude: "Better designed trials are needed to assess the benefits of methylphenidate".

Alternative treatments for ADHD include behavioural therapy and cognitive behavioural therapy. Read more about treatment options for ADHD.

Where did the story come from?

The study was carried out by researchers from a number of institutions, including the Region Zealand, University of Southern Denmark and Copenhagen University Hospital, all in Denmark.

Funding for the study was provided by the Psychiatric Research Unit, Region Zealand Psychiatry, Roskilde; Region Zealand Research Foundation; and the Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Copenhagen.

The peer-reviewed study was published by the Cochrane: Developmental, Psychosocial and Learning Problems Group. Like all Cochrane research, the study is open-access, so it is free to read online.

The review has been reported in much of the media as a warning to be cautious about over-prescribing such drugs. However, the Mail Online explained that the research team could not be confident about the results.

What kind of research was this?

This study was a systematic review and meta-analysis which aimed to assess the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD. This is a good way to gather and combine the findings from trials that have been conducted to date, to draw firmer conclusions; however, a systematic review can only be as good as the included studies.

What did the research involve?

This systematic review searched numerous literature databases and two trials registers to identify all randomised controlled trials (RCTs) comparing methylphenidate to inactive ("dummy") placebo, or no treatment in children and adolescents with ADHD aged 18 years or younger. At least 75% of participants in each study were required to have normal intellectual functioning.

Data was extracted from the studies for the following outcomes:

ADHD symptoms (attention, hyperactivity and impulsivity), short-term (within six months) or long-term (longer than six months)
serious adverse events
non-serious adverse events
general behaviour in school and at home
quality of life

Numerous study authors were responsible for data extraction and quality appraisal of the studies, which included an assessment of bias and differences in the results of the individual studies (heterogeneity).

Where appropriate, data from the different studies was pooled using meta-analysis to give an overall result.

What were the basic results?

The systematic review included 38 RCTs (5,111 participants) and 147 crossover trials (7,134 participants – crossover being where participants act as their own control, receiving treatment and no treatment).

The average age of participants across all studies was 9.7 years, but ranged from three to 18 years. As is frequently the case with ADHD, a larger number of boys were represented in the sample, with a boy-to-girl ratio of 5:1.

The length of methylphenidate treatment time ranged from one to 425 days, with an average of 75 days. All included trials were considered to be at high risk of bias.

In a pooled analysis of 19 trials, the researchers found that methylphenidate gave a slight improvement in teacher-rated ADHD symptoms when compared to placebo or no intervention. Those treated with methylphenidate had an average of 9.6 fewer points (95% confidence interval [CI] -13.75 to -6.38) on the ADHD Rating Scale (ADHD-RS).

The ADHD-RS is a scoring system, based on the variety and severity of symptoms, which has a range of 0 to 72 points. A change of 6.6 points is considered to represent the minimal relevant or clinically meaningful difference.

There was no evidence to suggest methylphenidate was associated with an increase in serious adverse events.

The number of non-serious adverse events was, however, higher in the methylphenidate group, with a 29% increase in the overall risk of any non-serious adverse events (relative risk [RR] 1.29, 95% CI 1.10 to 1.51). The most common non-serious adverse events were sleep problems and decreased appetite.

These side effects are acknowledged by the manufacturers of methylphenidate and are described as common in the patient information leaflets that come with the medication.

How did the researchers interpret the results?

The authors conclude: "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. Methylphenidate 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."

Conclusion

This is a well-conducted systematic review that aimed to assess the beneficial and harmful effects of methylphenidate (Ritalin being the most commonly known brand name) for children and adolescents with ADHD.

The review found that methylphenidate was associated with a slight improvement in the symptoms of ADHD, compared to placebo or no treatment – just on the borderline of what would be considered clinically meaningful. However, the researchers state this improvement should be weighed up against the increased risk of adverse events, such as sleeping problems and decreased appetite.

The review identified a large number of trials and included 12,245 children and adolescents, representing the gathering of extensive research into the effects of this drug. However, a major limitation is the poor-quality evidence that was available, with most trials being assessed as being of very low quality.

As the review authors suggest, more research with well-designed trials is needed to better assess the benefits and harms of the treatment, preferably with some subgroup analyses to see if it is possible to identify those who might have better or worse outcomes.

There is no cure for ADHD, but support and advice, and sometimes treatment in the form of medication or "talking" therapies can be useful, to make day-to-day life easier. Sometimes links may be noticed between symptoms and certain foods, such as sugar or additives. However, the most important thing is for the child to follow a balanced diet and not to make drastic changes or add supplements (e.g. omega 3 or 6 fatty acids) without first discussing with a GP.