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Clonidine for ADHD

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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

1. Mechanisms of action of clonidine

Clonidine is an alpha-2-adrenoceptor agonist.

  • Agonist of the σ-2A adrenoreceptor5
  • Agonist of the σ-2B adrenoreceptor5
  • Agonist of the σ-2C adrenoreceptor5

Clonidine is also an imidazoline receptor agonist.

If the dosage is too high and too fast (injected), clonidine can also act as a σ-1-adrenoceptor agonist.6

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.7
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).8

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.9

Clonidine and guanfacine are said to be helpful for rejection sensitivity in ADHD, according to a report by an American ADHD specialist.10

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:11

  • 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.12

2. Side effects

Side effects of clonidine have not yet been incorporated.

Clonidine has higher side effects than methylphenidate and atomoxetine.5
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.13


  1. Cortese, Adamo, Del Giovane, Mohr-Jensen, Hayes, Carucci, Atkinson, Tessari, Banaschewski, Coghill, Hollis, Simonoff, Zuddas, Barbui, Purgato, Steinhausen, Shokraneh, Xia, Cipriani (2018): Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis; The Lancet Psychiatry, VOLUME 5, ISSUE 9, P727-738, SEPTEMBER 01, 2018; Open Access; DOI:https://doi.org/10.1016/S2215-0366(18)30269-4 METASTUDY

  2. Nageye, Cortese (2019): Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD. Expert Rev Neurother. 2019 Jul;19(7):707-717. doi: 10.1080/14737175.2019.1628640. PMID: 31167583.)

  3. Faraone SV (2009): Using Meta-analysis to Compare the Efficacy of Medications for Attention-Deficit/Hyperactivity Disorder in Youths. P T. 2009 Dec;34(12):678-94. PMID: 20140141; PMCID: PMC2810184. METASTUDY

  4. Manohar, Kuppili, Kandasamy, Chandrasekaran, Rajkumar (2018): Implications of comorbid ADHD in ASD interventions and outcome: Results from a naturalistic follow up study from south India. Asian J Psychiatr. 2018 Mar 2;33:68-73. doi: 10.1016/j.ajp.2018.03.009., n = 50

  5. Guanfacin, Wirkstoff Aktuell, Ausgabe 2/2016, Stand 11.04.2015, Information der KBV

  6. Manz (2018): 05. Monoamine 2: Amphetamin, Ritalin (ADHS), Cocain, Tricyclika, Videovorlesung. ca. bei Minute 06:30.

  7. https://de.wikipedia.org/wiki/Adrenozeptor

  8. Steinhausen, Rothenberger, Döpfner (2010): Handbuch ADHS, Seiten 84, 85

  9. Nurse, Russell, Taljaard (1985): Effect of chronic desipramine treatment on adrenoceptor modulation of [3H]dopamine release from rat nucleus accumbens slices. Brain Res. 1985 May 20;334(2):235-42

  10. Dodson: How ADHD Ignites Rejection Sensitive Dysphoria; The extreme emotional pain of perceived rejection is a feeling unique to people with ADHD, and it can be debilitating. Learn how RSD may be impacting your patients; in: ADDitude. Strategies and Support für ADD & LD

  11. Vaidyanathan, Rajan, Chandrasekaran, Kandasamy (2019): Pre-school attention deficit hyperactivity disorder: 12 weeks prospective study. Asian J Psychiatr. 2019 Dec 14;48:101903. doi: 10.1016/j.ajp.2019.101903. n = 56

  12. Zeng KD, Wang GL, Yuan Y, Zhang W, Huang XH, Hu B (2023): Efficacy of clonidine in the treatment of children with tic disorder co-morbid with attention deficit hyperactivity disorder. Eur Rev Med Pharmacol Sci. 2023 May;27(9):4232-4238. doi: 10.26355/eurrev_202305_32333. PMID: 37203849.

  13. Manz (2018): 05. Monoamine 2: Amphetamin, Ritalin (ADHS), Cocain, Tricyclika, Videovorlesung.