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Ropinirole for ADHD


Ropinirole for ADHD

Ropinirole is a non-ergot dopamine agonist.
Ropinirole is a selective D2 agonist.

Ropinirole is often used as a Parkinson’s medication.

Dopamine inhibits prolactin. ADHD is based on a dopamine deficiency. Dopamine deficiency can lead to increased prolactin levels via the tuberoinfundibular dopamine system, which can mediate ADHD symptoms. More on this under The tuberoinfundibular system In the article The 5 dopaminergic systems of the brain.

As a dopamine agonist, ropinirole can help to reduce elevated prolactin levels.1

1. Ropinirole for ADHD

A small prospective study tested ropinirole against ADHD in 9 boys between the ages of 8 and 13.2
A very clear improvement in concentration was seen in 33% of the test subjects (2 out of 6).
In 84% of the subjects (5 out of 6), ropinirole improved impulsivity and the number of errors in the CPT between slightly and significantly. In 50% of the subjects (3 out of 6), the improvement in the number of errors was at least 40% of the initial number of errors without medication. In terms of impulsivity, ropinirole was on a par with MPH.

The number of subjects in this study is far too small to draw any reliable conclusions. However, the results indicate that ropinirole could be a helpful means of improving concentration and impulsivity in individual patients. Ropinirole could be considered for an individualized treatment trial, particularly in MPH and AMP non-responders. An individual case report on a 6-year-old boy with ADHD and restless legs, who was an MPH nonresponder, showed a good effect of ropinirole on ADHD and RLS.3

The side effect of ropinirole was severe daytime sleepiness, which was even more severe at 2 mg/day (3 out of 3 subjects) than at 1 mg/day (4 out of 6 subjects).
This could be an indication that ropinirole could be helpful for sleep problems in ADHD.

We suspect that ropinirole could be an option for ADHD sufferers who show elevated prolactin levels in the event of non-response to the usual ADHD medication.

2. Other D2 agonists

Other D2 agonists appear unsuitable for the treatment of ADHD.

2.1. Bromocriptine

Another D2 agonist that is also used for hyperprolactinemia is bromocriptine.
Bromocriptine also influences some serotonin and adrenoceptors.
In a study on attention problems after traumatic brain injury, bromocriptine showed no improvement.4
A case study reported a positive effect in ADHD sufferers with cocaine addiction only in the Digit Span test, which measures concentration.5 Bromocriptine was unable to reduce 6-OHDA-induced hyperactivity and impaired performance on an avoidance learning task.6

2.2. Cabergoline

Cabergoline is a strong D2 (Ki=0.61 nM in the striatum) and D3 agonist (Ki=1.27 nM in the striatum) as well as a 5-HT2B receptor agonist.78 Cabergoline is also said to have an affinity for D1.9
There are no studies on cabergoline in relation to ADHD.

A study on the effect of cabergoline on working memory compared to placebo:10

  • Cabergoline improved memory performance when no distractors were present
  • Cabergoline significantly reduced performance when distractors were present
  • Cabergoline did not alter memory performance when all items had to be remembered

Cabergoline increased impulsivity above the control value in a group of hyperprolactinemia sufferers, which was lower than the control value in untreated hyperprolactinemia sufferers.11 Overall, however, only the impulsivity measure of the Barratt Impulsivity Scale was altered. The other impulsivity measures were unchanged in all groups.
If these data can be reproduced, an elevated prolactin level could potentially be a biomarker for the ADHD-I subtype.

Overall, however, D2 agonists appear to carry the risk of increased impulsivity12

Cabergoline appears to cause less of an increase in hyperactivity than other dopamine agonists used to treat Parkinson’s disease.13

  1. Heneghan LJ, Tsang A, Dimino C, Khandji AG, Panigrahi SK, Page-Wilson G (2023): Ropinirole for the Treatment of Hyperprolactinemia: A Dose Escalation Study of Efficacy and Tolerability. J Clin Endocrinol Metab. 2023 Sep 16:dgad545. doi: 10.1210/clinem/dgad545. PMID: 37715962.

  2. Claus: (2013): Wirksamkeit und Verträglichkeit des Dopamin-Agonisten Ropinirol bei jungen Patienten mit Hyperkinetischer Störung, Dissertation

  3. Konofal, Arnulf, Lecendreux, Mouren (2005): Ropinirole in a child with attention-deficit hyperactivity disorder and restless legs syndrome. Pediatr Neurol. 2005 May;32(5):350-1. doi: 10.1016/j.pediatrneurol.2004.11.007. PMID: 15866437.

  4. Whyte J, Vaccaro M, Grieb-Neff P, Hart T, Polansky M, Coslett HB (2008): The effects of bromocriptine on attention deficits after traumatic brain injury: a placebo-controlled pilot study. Am J Phys Med Rehabil. 2008 Feb;87(2):85-99. doi: 10.1097/PHM.0b013e3181619609. PMID: 18209510.

  5. Cavanagh R, Clifford JS, Gregory WL (1989): The use of bromocriptine for the treatment of attention deficit disorder in two chemically dependent patients. J Psychoactive Drugs. 1989 Apr-Jun;21(2):217-20. doi: 10.1080/02791072.1989.10472161. PMID: 2668485.

  6. Shaywitz BA, Lipton SV, Teicher MH, Cohen DJ, Anderson GM, Batter DK, Young JG (1981): Effects of bromocriptine in developing rat pups after 6-hydroxydopamine. Pharmacol Biochem Behav. 1981 Sep;15(3):443-8. doi: 10.1016/0091-3057(81)90275-6. PMID: 6794039.

  7. doccheck Flexikon: Cabergolin

  8. Gerlach M, Double K, Arzberger T, Leblhuber F, Tatschner T, Riederer P (2003): Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum. J Neural Transm (Vienna). 2003 Oct;110(10):1119-27. doi: 10.1007/s00702-003-0027-5. PMID: 14523624.

  9. Brusa L, Pavino V, Massimetti MC, Bove R, Iani C, Stanzione P (2013): The effect of dopamine agonists on cognitive functions in non-demented early-mild Parkinson’s disease patients. Funct Neurol. 2013 Jan-Mar;28(1):13-7. PMID: 23731911; PMCID: PMC3812723.

  10. Fallon SJ, Zokaei N, Norbury A, Manohar SG, Husain M (2017): Dopamine Alters the Fidelity of Working Memory Representations according to Attentional Demands. J Cogn Neurosci. 2017 Apr;29(4):728-738. doi: 10.1162/jocn_a_01073. PMID: 27897674; PMCID: PMC5889096.

  11. Barake M, Evins AE, Stoeckel L, Pachas GN, Nachtigall LB, Miller KK, Biller BM, Tritos NA, Klibanski A (2014): Investigation of impulsivity in patients on dopamine agonist therapy for hyperprolactinemia: a pilot study. Pituitary. 2014 Apr;17(2):150-6. doi: 10.1007/s11102-013-0480-6. PMID: 23504371; PMCID: PMC4109390. n = 30

  12. Hamidianjahromi A, Tritos NA (2022): Impulse control disorders in hyperprolactinemic patients on dopamine agonist therapy. Rev Endocr Metab Disord. 2022 Oct;23(5):1089-1099. doi: 10.1007/s11154-022-09753-6. PMID: 36125673. REVIEW

  13. Arai N, Isaji M, Miyata H, Fukuyama J, Mizuta E, Kuno S (1995):Differential effects of three dopamine receptor agonists in MPTP-treated monkeys. J Neural Transm Park Dis Dement Sect. 1995;10(1):55-62. doi: 10.1007/BF02256629. PMID: 8619909.

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