Clonidine as a Treatment of Behavioural Disturbances in Autism Spectrum Disorder: A Systematic Literature Review

Background: Agitation and aggression are commonly cited reasons for psychiatry consultation for individuals diagnosed with autism spectrum disorder (ASD). While risperidone and aripiprazole do not carry Health Canada approval for management of ASD-associated irritability, both are used for this indication but are not universally effective and carry substantial risk of adverse effects. This necessitates use of off-label medications to assist in management of behavioral dysregulation. Clonidine, an alpha-2 receptor agonist, is approved in Canada for treatment of hypertension. The evidence base also supports its use for attention deficit/hyperactivity disorder (ADHD) and for tics in Tourette's disorder. This review focuses on examining the literature regarding clonidine as a treatment of challenging behaviours in the ASD population. Method: Systematic search of MEDLINE, EMBASE, and PsycINFO databases resulted in 540 unique records. Ten publications were relevant to this review. Results: Two cross-over studies, one open-label case series, and seven case reports were identified. One of two controlled studies suggested benefit from clonidine versus placebo. Caregivers typically noted improvement in behaviour with clonidine versus baseline. Clonidine was generally well-tolerated. Sedation was the most consistently reported adverse effect. Despite being an anti-hypertensive medication, few discontinued clonidine due to hypotension or bradycardia. Conclusion: Clonidine has a limited evidence base for use in the management of behavioural problems in patients with ASD. Most evidence originates from case reports. Given the paucity of pharmacological options for addressing challenging behaviours in ASD patients, a clonidine trial may be an appropriate and cost-effective pharmaceutical option for this population.