Clonidine for ADHD

Clonidine is an alpha-2 agonist.
Trade names of clonidine are:

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

Clonidine is available in immediate release and sustained release.
Sustained release clonidine is approved by the FDA for the treatment of ADHD for children 6 years of age and older.¹ Two doses per day are required for all-day coverage.
Immediate release clonidine is used off-label for people with ADHD who have difficulty swallowing tablets. Immediate release clonidine must be taken 4 to 4 times a day.

Clonidine is a rather atypical medication for ADHD.

Effect sizes in relation to ADHD:

• 0.71 for children and adolescents², which seems to us to be too high and due to an insufficient number of studies³
• 0.03 (meta-analysis)⁴

Clonidine is commonly used for autism spectrum disorders and may be helpful for comorbid ASD + ADHD in young children.⁵
There are 12 evidence-based guidelines on the use of clonidine at⁶

• 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 acts in the PFC⁷ as:

• Σ-2A-adrenoreceptor agonist⁸⁷
• Σ-2B-adrenoreceptor agonist⁸⁷
• Σ-2C-adrenoreceptor agonist⁸⁷
• Imidazoline receptor agonist
• Σ-1-adrenoceptor agonist with too fast, too high dosage (injected)⁹

Clonidine weakens the effect of adrenaline.

Alpha-2-adrenoceptors are activated endogenously by the neurotransmitters adrenaline and noradrenaline. They are therefore responsible for the effects mediated by adrenaline and noradrenaline.¹⁰
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).¹¹

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.¹²

Clonidine and guanfacine are said to be helpful for rejection sensitivity in ADHD.¹³

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:¹⁴

• 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.¹⁵

The optimum dosage for children and adolescents should be 0.9 mg / kg / day.¹⁶

2. Side effects¶

Clonidine has higher side effects than methylphenidate and atomoxetine.⁸

Side effects of clonidine are dose-dependent, in particular¹

• Sedation*
• Daytime tiredness*
• Drop in blood pressure*
• Bradycardia and hypotension, especially with renal dysfunction
• Vascular damage and thrombosis, especially in older people with endothelial damage (damage to the inner layer of blood vessels)¹⁷

*These side effects may decrease after dosing.¹⁸
Dosing in and dosing out should be slow and gradual.¹ To avoid rebound hypertension, it is recommended that clonidine be reduced every 3 to 7 days at a dose of 0.1 mg per day until it is discontinued.¹⁸

The sedative effect can also be used positively by administering higher doses before going to bed.¹