Which ADHD medications are least likely to be associated with headaches?

There is strong evidence of the effectiveness of a variety of ADHD medicines in reducing ADHD symptoms. While some are more effective than others, another factor in deciding on a course of treatment is minimizing noxious side effects.

One of those side effects is a headache.

An international team of researchers from Sweden, Germany, the Netherlands, the United Kingdom, the United States, and Australia conducted a systematic review of the peer-reviewed medical literature about ADHD and headaches on the one hand, and ADHD medications and headaches on the other.

As a baseline, they performed a meta-analysis of twelve studies with a combined total of over 2.7 million participants that compared headache rates between youths with and without ADHD. Those with ADHD were twice as likely to suffer from headaches. This held even after limiting the meta-analysis to the four studies that adjusted for confounders.

Breaking down the results by type of headache revealed a fascinating distinction. There was no significant difference in rates of tension headaches, but migraines were 2.2 times as frequent among youths with ADHD.

This strong association between ADHD and migraines suggests looking for medications that are both effective and unlikely to further contribute to the odds of migraine.

Accordingly, the team examined associations between specific ADHD medications and headaches.

Stimulant medications are generally considered the most effective medications for treating ADHD. A meta-analysis of ten studies with 2,672 participants found no association between amphetamines and headaches. On the other hand, a meta-analysis of 17 studies with 3,371 participants found that methylphenidate increased the odds of headache by one-third (33%).

The non-stimulant atomoxetine is usually considered a second-tier treatment for those among whom stimulants are contraindicated. A meta-analysis of 22 studies encompassing 3,857 participants found it increased the odds of headache by 29%.

Guanfacine fared worst of the bunch. A meta-analysis of eight studies combining 1,956 participants found it increased the odds of headache by 43%.

Finally, a meta-analysis of six studies with a combined total of 818 participants found no association with headaches.

There was no indication of publication bias in any of the meta-analyses.

Pei-Yin Pan, Ulf Jonsson, Sabriye Selin ŞahpazoğluÇakmak, Alexander Häge, Sarah Hohmann, Hjalmar Nobel Norrman, Jan K. Buitelaar, Tobias Banaschewski, Samuele Cortese, David Coghill, and Sven Bölte, “Headachein ADHD as comorbidity and a side effect of medications: a systematic review and meta-analysis,” Psychological Medicine(2021), published online,https://doi.org/10.1017/S0033291721004141.