Clonidine for ADHD

Clonidine is available in immediate release and sustained release.
Trade names of clonidine are:

• Catapresan (A, D, CH)
• Haemiton (D)
• Isoglaucon (A, D)
• Paracefan (D)
• Kapvay (USA; prolonged-release clonidine hydrochloride):

Clonidine is a rather atypical medication for ADHD.
The stated Effect size of 0.71 for children and adolescents¹ seems too high and is due to an insufficient number of studies.² Another meta-analysis found an Effect size of 0.03.³

Clonidine is commonly used in autism spectrum disorders and may be helpful in comorbid ASD + ADHD in young children.⁴
There are 12 evidence-based guidelines on the use of clonidine at⁵

• High blood pressure: 1
• Substance abuse: 4
• Menopause: 4
• Restless legs: 2
• Tourette: 1
• ADHD: none
• Migraine prophylaxis: none

• 1. Mechanisms of action of clonidine
• 2. Side effects

1. Mechanisms of action of clonidine¶

Clonidine is an alpha-2-adrenoceptor agonist.

• Agonist of the σ-2A adrenoreceptor⁶
• Agonist of the σ-2B adrenoreceptor⁶
• Agonist of the σ-2C adrenoreceptor⁶

Clonidine is also an imidazoline receptor agonist.

If the dosage is too high too quickly (injected), clonidine can also act as a σ-1-adrenoceptor agonist.⁷

Clonidine weakens the effect of adrenaline.

Alpha-2 adrenoceptors are activated by the neurotransmitters adrenaline and noradrenaline. They are therefore responsible for the effects mediated by adrenaline and noradrenaline.⁸
Alpha-2-A receptor agonists such as clonidine and guanfacine are thought to enhance a phasic release of noradrenaline in the nucleus coeruleus, which improves attention as well as working memory and visuomotor-associated learning (as opposed to a long-term tonic release of noradrenaline, which impairs performance).⁹

Clonidine thus has a noradrenergic effect.

As an alpha-2-adrenoceptor agonist, clonidine (like guanfacine) significantly reduces the release of dopamine in the nucleus accumbens in the laboratory.¹⁰

Clonidine and guanfacine are said to be helpful for rejection sensitivity in ADHD, according to a report by an American ADHD specialist.¹¹

A 2019 study from India reported that clonidine was the most commonly used medication for ADHD in a group of children aged 3 to 6 years with ADHD:¹²

• Clonidine: 44, 6 %
• Risperidone: 28.7 %
• Methylphenidate: 10.7 %
• Atomoxetine: 10.7 %

Clonidine worked better than methylphenidate with halperidol in children with ADHD and comorbid tic disorders.¹³

2. Side effects¶

Side effects of clonidine have not yet been incorporated.

Clonidine has higher side effects than methylphenidate and atomoxetine.⁶
Older people may have more frequent endothelial damage (damage to the inner layer of blood vessels). In these people, clonidine could increase the risk of vascular damage and thrombosis.¹⁴