Headache in ADHD as comorbidity and a side effect of medications: a systematic review and meta-analysis.

Pei-Yin Pan,Alexander Häge,Sabriye Selin Şahpazoğlu Çakmak,Samuele Cortese,Hjalmar Nobel Norrman,Jan K Buitelaar,Tobias Banaschewski,Sven Bölte,David Coghill,Sarah Hohmann,Ulf Jonsson

doi:10.1017/s0033291721004141

Abstract

There is mixed evidence on the association between headache and attention-deficit/hyperactivity disorder (ADHD), as well as headache and ADHD medications. This systematic review and meta-analysis investigated the co-occurrence of headache in children with ADHD, and the effects of ADHD medications on headache. Embase, Medline and PsycInfo were searched for population-based and clinical studies comparing the prevalence of headache in ADHD and controls through January 26, 2021. In addition, we updated the search of a previous systematic review and network meta-analysis of double-blind randomized controlled trials (RCTs) on ADHD medications on June 16, 2020. Trials of amphetamines, atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with a placebo arm and reporting data on headache as an adverse event, were included. Thirteen epidemiological studies and 58 clinical trials were eligible for inclusion. In epidemiological studies, a significant association between headache and ADHD was found [odds ratio (OR) = 2.01, 95% confidence interval (CI) = 1.63-2.46], which remained significant when limited to studies reporting ORs adjusted for possible confounders. The pooled prevalence of headaches in children with ADHD was 26.6%. In RCTs, three ADHD medications were associated with increased headache during treatment periods, compared to placebo: atomoxetine (OR = 1.29, 95% CI = 1.06-1.56), guanfacine (OR = 1.43, 95% CI = 1.12-1.82), and methylphenidate (OR = 1.33, 95% CI = 1.09-1.63). The summarized evidence suggests that headache is common in children with ADHD, both as part of the clinical presentation as such and as a side effect of some standard medications. Monitoring and clinical management strategies of headache in ADHD, in general, and during pharmacological treatment are recommended.

Highlights

Headache in childhood is common and disabling
The comparison group comprised of 2 464 878 participants, all recruited from the community
Despite the heterogeneity across studies in the meta-analysis of crude data, the association survived when pooling odds ratio (OR) adjusted for possible confounders, including age, sex, and socioeconomic status (Bigal & Lipton, 2006)

Summary

Introduction

Headache in childhood is common and disabling. The estimated prevalence during 1 month to lifetime is 58.4%; migraine affects 7.7% (Abu-Arafeh, Razak, Sivaraman, & Graham, 2010). Pediatric headaches have been linked to sleep problems (Dosi et al, 2013; Esposito, Parisi, Miano, & Carotenuto, 2013), emotional dysfunction (Arruda & Bigal, 2012a; Fuh et al, 2010), impaired peer relations (Karwautz et al, 1999), and poor academic performance (Arruda & Bigal, 2012b; Genizi et al, 2013). Its clinical management is challenging due to the multifactorial origin and co-existing medical and psychiatric conditions (Bellini et al, 2013; Guidetti, Faedda, & Siniatchkin, 2016; Whitehouse & Agrawal, 2017)

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Results

Conclusion