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ONYDA XR for ADHD is pronounced oh nee dah

A third formulation of the alpha-2 agonist clonidine will soon be available.

Catapres was the original brand of clonidine, available since 1966 as an immediate-release tablet, approved for hypertension and used off label for ADHD.

Clonidine ER (Kapvay), extended release tablet, was released in 2010 for childhood ADHD. Kapvay is used off label for adult ADHD and is available as a generic medication.

Clonidine ER oral suspension (Onyda XR) was approved in 2024 for childhood ADHD, ages 6 through 17. It will be much more expensive than clonidine IR and ER tablets.

Clonidine Catapres Clonidine ER Kapvay and Onyda-XR mnemonics
Mascots for the 3 types of clonidine

Clonidine in general

Clonidine is a centrally acting alpha-2 adrenergic (norepinephrine) receptor agonist, FDA-approved for hypertension. “Central” refers to the central nervous system (CNS). Stimulation of alpha-2 autoreceptors reduces norepinephrine (NE) release as a negative feedback mechanism. Reduction of NE allows peripheral arteries to relax, which lowers blood pressure. 

Alpha-1 receptors (postsynaptic) generally have opposing actions to alpha-2 receptors (presynaptic). Blood pressure is reduced by alpha-2 agonists like clonidine and also reduced by alpha-1 antagonists like prazosin.

Clonidine is rarely used as a first-line medication for hypertension but would be a reasonable first-line antihypertensive for those with one of the following comorbid conditions, to kill two birds with one stone.

Clonidine is a drug of choice for the treatment of hypertensive urgencies. Only stop clonidine by tapering. If clonidine is stopped abruptly, rebound hypertension may result, possibly leading to a hypertensive crisis.

Psychiatrists have found many off-label therapeutic uses of clonidine:


Clonidine is considered safe and effective for childhood ADHD. It may be used as an alternative to or in combination with a stimulant. Clonidine is more effective for treatment of hyperactivity than for inattention. It is typically dosed BID for this indication. Onset of effect may be delayed by 2–4 weeks and effect size is less than seen with stimulants. In 2018 an extended-release formulation of clonidine (KAPVAY) was released for treatment of ADHD in children. Guanfacine (Tenex), another central alpha-2 agonist for ADHD, is generally less sedating than clonidine. 

Intermittent explosive disorder / Oppositional defiant disorder

Clonidine is useful in management of aggressive individuals who are highly irritable and impulsive. For violent children, consider trying clonidine before resorting to an antipsychotic. 

Opioid withdrawal 

Clonidine is a second-line treatment for opioid withdrawal (behind buprenorphine). A clonidine transdermal patch can be applied with additional PO doses throughout the day as tolerated. Another central alpha-2 agonist—lofexidine (Lucemyra)—is specifically approved for opioid withdrawal but it is expensive. 

Tics/Tourette’s disorder

Alpha-2 agonists are considered first-line for the treatment of tics. For Tourette’s disorder, it is best to try clonidine prior to FDA-approved medications (antipsychotics). 

Hot flashes

Clonidine can alleviate hot flashes/flushes, including those caused by SSRIs.

Sialorrhea (hypersalivation) 

A side effect of clonidine is dry mouth, so it is suitable to counteract clozapine-induced hypersalivation. This should be done cautiously, because clozapine and clonidine both decrease blood pressure.


Clonidine has utility in mania as an adjunct to a mood stabilizer and/or antipsychotic.

Dosing of clonidine ER suspension (ONYDA XR):

For patients switching from another clonidine product, discontinue that treatment, and titrate with ONYDA XR using the titration schedule. Do not substitute for other clonidine products on a mg-per-mg basis because of differing pharmacokinetic profiles. The starting dosage of ONYDA XR is 0.1 mg orally once daily at bedtime with or without food. Titrate the dose in increments of 0.1 mg per day at weekly intervals depending on clinical response up to the maximum recommended dosage of 0.4 mg once daily at bedtime. When ONYDA XR is added to a CNS stimulant, adjust the dose of the CNS stimulant depending on the clinical response to ONYDA XR.

Copyright 2024 CaferMed, intended for prescribers

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