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The two FDA-approved non-stimulant medications for Attention-Deficit/Hyperactivity Disorder (ADHD) that function as alpha-2 adrenergic agonists are guanfacine and clonidine [1]. These drugs primarily modulate norepinephrine activity in the prefrontal cortex to improve attention and impulse control, distinguishing them from stimulants and serotonin-norepinephrine reuptake inhibitors (SNRIs) like atomoxetine [2]. Guanfacine is marketed under the brand name Intuniv specifically for ADHD treatment in children and adolescents aged 6-17 years [3]. The FDA-approved formulation for this indication is the extended-release (ER) tablet, which provides once-daily dosing to maintain steady plasma levels and minimize side effects such as sedation or hypotension compared to immediate-release versions used for hypertension [4]. Intuniv is not approved in immediate-release form for ADHD, as the ER mechanism ensures gradual release over 24 hours, enhancing tolerability and efficacy [3]. Clonidine is marketed under the brand name Kapvay for ADHD, approved for use in children aged 6-17 years, either as monotherapy or adjunct to stimulants [5]. Similar to guanfacine, the required formulation is extended-release tablets, designed for twice-daily dosing to achieve sustained therapeutic effects while reducing peak-related adverse events like drowsiness [6]. Immediate-release clonidine, typically for hypertension, lacks FDA approval for ADHD due to its pharmacokinetic profile not supporting consistent symptom management [5]. Both medications require careful titration and monitoring for cardiovascular effects, with ER formulations being essential for their ADHD-specific labeling and safety profile [1][2]. (Word count: 248) ## References [1] FDA. (2023). Drugs@FDA: FDA-Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/ [2] American Academy of Pediatrics. (2022). ADHD: Clinical Practice Guideline. https://publications.aap.org/pediatrics/article/144/4/e20192528/81594 [3] FDA. (2009). Intuniv (guanfacine) Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022037lbl.pdf [4] National Institute of Mental Health. (2023). Attention-Deficit/Hyperactivity Disorder. https://www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder-adhd [5] FDA. (2010). Kapvay (clonidine) Label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022331s001s002lbl.pdf [6] Child Mind Institute. (2023). Non-Stimulant Medications for ADHD. https://childmind.org/article/non-stimulant-medications-available-for-adhd-treatment/

The two FDA-approved non-stimulant medications for ADHD that function as alpha-2 adrenergic agonists are guanfacine and clonidine. Guanfacine is marketed under the brand name Intuniv specifically for ADHD treatment, and it is only approved in an extended-release formulation [1]. This extended-release mechanism allows for once-daily dosing and steady medication levels throughout the day, which is essential for managing ADHD symptoms effectively. The immediate-release form of guanfacine, marketed as Tenex, is indicated for hypertension and not approved for ADHD [2]. The second agent, clonidine, is approved for ADHD under the brand name Kapvay, which is a twice-daily extended-release tablet designed specifically for ADHD management [3]. Similar to guanfacine, the immediate-release version of clonidine (Catapres) is used primarily for hypertension and lacks FDA approval for ADHD [4]. Both Intuniv and Kapvay target postsynaptic alpha-2A adrenergic receptors in the prefrontal cortex, enhancing working memory, attention, and behavioral inhibition. Their extended-release formulations are critical to maintaining consistent therapeutic effects and minimizing side effects such as sedation or blood pressure fluctuations. These medications are particularly useful for patients who do not respond to or cannot tolerate stimulants or SNRIs [5]. ## References [1] FDA approval label for Intuniv (guanfacine extended-release). [2] National Institute of Mental Health – ADHD Treatment Options. [3] FDA approval label for Kapvay (clonidine extended-release). [4] Lexicomp, Drug Information Handbook. [5] UpToDate – Pharmacologic Treatment of ADHD in Children and Adults.