Association between central nervous system stimulants used to treat attention deficit hyperactivity disorder (ADHD) and Raynaud's phenomenon: A scoping review

Abstract

The association between central nervous (CNS) stimulants used to treat attention deficit hyperactivity disorder (ADHD) and Raynaud's phenomenon (RP) has received little attention to date. Our aim was to map the existing literature on aetiopathogenesis, clinical presentation and management of peripheral vasculopathy, with a focus on RP, secondary to drug therapy for ADHD. We searched the PubMed® database (01/11/1951 to 01/08/2020) and included articles written in English, which focussed on CNS stimulants used to treat ADHD and RP. The search identified 150 articles 9 of which were eligible for inclusion (70 patients). The majority of studies (n = 6) related to children or adolescents; however, adult cases were also identified. Peripheral vascular manifestations included attacks of RP (new and worsening) and cold sensitivity (acrocyanosis and perniosis). Irreversible ischaemic complications including digital autoamputation and lower limb critical digital ischaemia have also been reported. The implicated causative CNS stimulants were Methylphenidate (n = 5), Dextroamphetamine (n = 4), Atomoxetine (n = 2), and Lisdexamphetamine (n = 2). Complete resolution of RP symptoms was observed in half (n = 5) of studies upon drug cessation. Other therapeutic strategies have included dose reduction and switching to an alternative drug therapy. A potential autoimmune association has also been postulated including drug-induced autoimmunity and new cases of systemic sclerosis which have been potentially attributed to treatment. Future research is required to understand the association between CNS stimulant drug therapies for ADHD and peripheral vascular manifestations, including RP.

Keywords: Attention deficit hyperactivity disorder; Central nervous system stimulants; Peripheral ischaemia; Raynaud's phenomenon; Systemic sclerosis; Vasculopathy.