New systematic review links long-term use of ADHD drugs to impaired fertility in mammals

Researchers from the Nordic Cochrane Centre have reviewed animal studies for effects of long-term use of drugs against Attention Deficit Hyperactivity Disorder (ADHD). The findings show that long-term use may impair the reproductive system, with some studies showing delayed sexual maturation. There were a total of 17 studies available, published between 1975 and 2016, where 13 were rat trials.

What are the long-term effects of ADHD medication on children? Do the benefits of the medication outweigh the harms in long-term use?

These were some of the questions a team of researchers from the Nordic Cochrane Centre set out to answer through a systematic review of human studies, but they discovered that there was not much data apart from a large trial with a 16-year follow-up with pretty negative results[1]. They therefore needed to go one step further by looking at animal studies to gain insights in to the effects of long term use of ADHD medication.

"Millions of children and young people around the world are on prescription medication for ADHD symptoms, and a lot of people end up taking them for many years. Unfortunately, there are very few human studies on the long-term effects of ADHD pills, but we know that there is a documented effect on the endocrine system and that the drugs suppress growth. Therefore, we decided to investigate if ADHD pills also affect fertility”, explains PhD student Pia Brandt Danborg, from the Nordic Cochrane Centre.

High quality research evidence on ADHD medication is needed When investigating mammalian fertility studies, the researchers found that 15 out of the 17 studies used placebo for the control group, a prerequisite for good study conduct, but that the studies were generally not of high quality.

Nine of the studies involved methylphenidate (Ritalin), the most commonly used drug. The researchers found that methylphenidate delayed puberty and resulted in fewer oestrous cycles in female mammals. The impairment on fertility was less if treatment started late, and the harms lessened after a treatment-free period.

"It is likely that these injuries to some extent also occur in the human reproductive system. However, it is worth noting that the research settings are not similar to human conditions, as ADHD treatments on animals started earlier than what is normal for humans. On the other hand, the treatment period was shorter compared to treatments in humans. We therefore need to look at the long-term effects on fertility in humans. We also need to be more cautious in prescribing these stimulants to children diagnosed with ADHD symptoms, as they do not seem to be beneficial in the long run,” says Pia Brandt Danborg.

The study has been published in the scientific journal International Journal of Risk & Safety in Medicine.

[1]Swanson JM, et al. J Child Psychol Psychiatry 2017;58:663-78.