Guanfacine
Guanfacine is an alpha-adrenergic agonist that is typically used in children with attention deficit hyperactivity disorder (ADHD) who have not responded to or who cannot tolerate stimulant medications or atomoxetine. In children, a number of randomized controlled trials have demonstrated efficacy of guanfacine compared to placebo, and the available evidence suggests an acceptable safety profile.[139]Sallee FR, McGough J, Wigal T, et al. Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial. J Am Acad Child Adolesc Psychiatry. 2009 Feb;48(2):155-65.
http://www.ncbi.nlm.nih.gov/pubmed/19106767?tool=bestpractice.com
[140]Wilens TE, Bukstein O, Brams M, et al. A controlled trial of extended-release guanfacine and psychostimulants for attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2012 Jan;51(1):74-85.e2.
http://www.ncbi.nlm.nih.gov/pubmed/22176941?tool=bestpractice.com
In adults, evidence on guanfacine is limited and more studies are needed before its use can be recommended as part of standard practice in this population group.[141]Radonjić NV, Bellato A, Khoury NM, et al. Nonstimulant medications for attention-deficit/hyperactivity disorder (ADHD) in adults: systematic review and meta-analysis. CNS Drugs. 2023 May;37(5):381-97.
http://www.ncbi.nlm.nih.gov/pubmed/37166701?tool=bestpractice.com
In adults, guanfacine is associated with a number of adverse effects, including hypotension, somnolence, postural dizziness, and constipation.[142]Iwanami A, Saito K, Fujiwara M, et al. Efficacy and safety of guanfacine extended-release in the treatment of attention-deficit/hyperactivity disorder in adults: results of a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2020 Apr 14;81(3):19m12979.
https://www.psychiatrist.com/jcp/neurodevelopmental/adhd/guanfacine-extended-release-improves-adhd-symptoms-in-japanese-adults
http://www.ncbi.nlm.nih.gov/pubmed/32297719?tool=bestpractice.com
Viloxazine
Viloxazine is a selective norepinephrine-reuptake inhibitor that was initially developed as an antidepressant in the 1970s. An extended-release formulation of viloxazine was approved for the treatment of ADHD in children ages 6 to 17 years in the US in 2021. It has now also been approved for the treatment of ADHD in adults, and is the first novel nonstimulant option to be approved in the US for ADHD in adults in 20 years. In phase 3 clinical trials, viloxazine improved ADHD symptoms compared to placebo and was generally well tolerated. Somnolence, decreased appetite, and headache were the most commonly reported adverse events.[143]Nasser A, Liranso T, Adewole T, et al. A phase Ill, randomized, placebo-controlled trial toassess the efficacy and safety of once-daily SPN-812 (viloxazine extended-release) in thetreatment of attention-deficit /hyperactivity disorder in school-age children. Clin Ther. 2020Aug;42(8):1452-66.
https://www.doi.org/10.1016/j.clinthera.2020.05.021
http://www.ncbi.nlm.nih.gov/pubmed/32723670?tool=bestpractice.com
[144]Nasser A, Liranso T, Adewole T, et al. A phase 3, placebo-controlled trial of once-daily viloxazine extended-release capsules in adolescents with attention-deficit/hyperactivitydisorder. J Clin Psychopharmacol. 2021 Jul-Aug 01;41(4):370-80.
https://www.doi.org/10.1097/JCP.0000000000001404
http://www.ncbi.nlm.nih.gov/pubmed/34181360?tool=bestpractice.com
[145]Nasser A, Liranso T, Adewole T, et al. A phase 3 placebo-controlled trial of once-daily 400-mg and 600-mg SPN-812 (viloxazine extended-release) in adolescents with ADHD. Psychopharmacol Bull. 2021 Mar 16;51(2):43-64.
http://www.ncbi.nlm.nih.gov/pubmed/34092822?tool=bestpractice.com
[146]Nasser A, Liranso T, Adewole T, et al. Once-daily SPN-812 200 and 400 mg in the treatment of ADHD in school-aged children: a phase III randomized, controlled trial. Clin Ther. 2021 Apr;43(4): 684-700
https://www.doi.org/10.1016/j.clinthera.2021.01.027
http://www.ncbi.nlm.nih.gov/pubmed/33750646?tool=bestpractice.com
Based on clinical study data, viloxazine is associated with an increased risk of suicidal thoughts and behavior compared to placebo. Patients treated with viloxazine therefore need to be closely monitored for clinical worsening, and for emergence of suicidal thoughts and behaviors. Viloxazine is not approved or available in Europe.