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Other medications for ADHD


Other medications for ADHD

In this article, we summarize - for the sake of completeness - other medications that have been mentioned in individual publications in connection with ADHD, but are not widely used or discussed for the treatment of ADHD.

1. Other primary dopaminergic drugs

1.1. Risperidone

Use in mentally retarded children with ADHD-HI and aggressive behaviors (according to the German Medical Association).1
Dosage: low (0.5 to 1.5 mg/day divided into two doses).1

Risperidone blocks (albeit only 1/3 compared to haloperidol (brand: Haldol)) the dopamine D2 receptor and thus has antipsychotic effects.

A placebo-controlled trial of the efficacy of risperidone or divalproex sodium in children with ADHD in relation to residual aggressive behavior after optimal adjustment to stimulants. A high response rate during the open-label stimulant optimization phase of the study suggests that rigorous titration of stimulant medication and concurrent behavioral therapy may avoid the need for additional medication. If this did not already result in symptom remission of the aggressive behavior, risperidone such as divalproex sodium were effective adjunctive therapies. Risperidone was associated with weight gain.2 Another study of divalproex reached similar results.3

The mention in the context of ADHD probably comes from a temporary applicability in cases of massive aggression. Positive effects have been reported in cases of comorbid aggression in addition to ADHD.45

On the problem of D2 receptor blockade in ADHD, see ⇒ General notes on antipsychotics as D2 antagonists in ADHD.

In any case, risperidone is not suitable for the classic medication of ADHD (without underachievement or aggressiveness).

1.2. Isoproterenol / Isoprenaline

Isoproterenol is a beta-adrenoreceptor agonist. Above a certain dosage, isoproterenol strongly increases dopamine release in the nucleus accumbens.6

Use as ADHD medication hardly known.

1.3. Gingko extract EGb 761

One study claimed a selective increase in dopamine levels in the PFC for 40 to 180 minutes after ingestion by up to 63%, but only in the context of long-term ingestion, not short-term administration of EGb 761 (100mg/kg). At the same time, norepinephrine levels had increased by up to 20%. Serotonin levels did not change. It had caused an improvement in learning abilities.7

Whether there is an improvement on ADHD symptoms, or whether, as with levodopa, which also increases dopamine levels, there is no effect in ADHD, has not been described.

Use as a medication for ADHD should not be made prior to further investigation, especially since the study apparently was not conducted in a peer-reviewed journal, indicating that a rigorous review process, as is customary in peer-reviewed journals, was not conducted.

1.4. Baikal

Studies address a reduction in hyperactivity symptoms by Baikalin in rats.89

Baikalin, like MPH, appears to be able to regulate the motor skills and learning and memory abilities of SHR rats with ADHD-HI, thereby improving the core symptoms of ADHD-HI, i.e., hyperactivity, impulsive behavior, and inattention. Baikalin has a dose-dependent effect. Compared to MPH, it takes a longer time to exert its therapeutic effect.10

Baikalin could exert a therapeutic effect in AD(HHD) through

  • Increase dopamine levels in the striatum (whereas MPH increases dopamine in the PFC and striatum)11
  • Upregulation of the AC / cAMP / PKA pathway12

It seems to be the same authors or the same main author. Publications by other authors on Baikalin in ADHD could not be found. Prior to verification by several different author teams and review in humans, the results should not be used to try Baikalin as a drug in humans.

1.5. Amphetaminil

Trade name: AN1

Amphetamine / methamphetamine-like agent that is metabolized by the body to amphetamine. Mentioned as an ADHD drug, but completely uncommon and hardly documented.13

1.6. Droxidopa

Droxidopa (L-threo-dihydroxyphenylserine, L-DOPS) is a prodrug of dopamine and norepinephrine. It can cross the blood-brain barrier and is converted to dopamine and norepinephrine in the brain.

USA: Northera (since 2014)
Japan: DOPS (since 1989)
Switzerland: no approval so far

Droxidopa is considered an orphan drug.

A combination of droxidopa and benserazide, a peripheral amino acid decarboxylase inhibitor, had a stimulatory effect on the PFC and inhibited dopaminergic neurons in rats. Further, in juvenile SHR/NCrl rats, which serve as an animal model of ADHD-C, showed:14

  • Hyperactivity reduced
  • Impulsivity reduced
  • Inattention reduced

In juvenile WKY/NCrl rats, which serve as an animal model of ADHD-I subtype, administration of droxidopa with benserazide induced:14

  • Impulsivity reduced
  • Inattention unchanged

Its use for the treatment of ADHD in humans has not yet been researched and is therefore not recommended.

(1.7. Pemolin)

Pemoline is said to have had a comparable effect to MPH.1516

It was withdrawn from the market in 2006 due to liver-damaging effects.

Former trade names: Cylert, Stimul, Tradon

2. Other drugs with primarily other modes of action

2.1. Sertraline

  • Predominantly serotonergic.
  • Sigma-1 antagonist
    • Worsens psychotic symptoms17

Use of sertraline as an ADHD drug poorly known.

2.2. Axura / Ebixa

Axura /Ebixa are dementia medications.
They are predominantly glutamatergic in action.

As ADHD medications, they are rarely used.

2.3. Selegiline

Selegiline is an MAO inhibitor used primarily in Parkinson’s disease. At low doses, it is a selective MAO-B inhibitor.

Brand names: Movergan, Antiparkin, Xilopar as well as generic

Selegiline is also reportedly used off-label for ADHD.18
We are not aware of any content in this regard.

2.4. Opipramol

Opipramol is a primarily anxiolytic (anti-anxiety) tricyclic antidepressant.

Opipramol binds strongly to sigma-1 and sigma-2 receptors, but does not inhibit reuptake of biogenic amines like usual TCAs. Subtherapeutic doses decrease sigma-2 receptor density.17

  1. Empfehlungen der Bundesärztekammer zur Therapie und Versorgung von AD(H)S, Abschnitt

  2. Blader, Pliszka, Kafantaris, Foley, Carlson, Crowell, Bailey, Sauder, Daviss, Sinha, Matthews, Margulies (2020): Stepped Treatment for Attention-Deficit/Hyperactivity Disorder and Aggressive Behavior: A Randomized, Controlled Trial of Adjunctive Risperidone, Divalproex Sodium, or Placebo After Stimulant Medication Optimization. J Am Acad Child Adolesc Psychiatry. 2020 Jan 30:S0890-8567(20)30064-2. doi: 10.1016/j.jaac.2019.12.009. PMID: 32007604; PMCID: PMC7390668. n = 175

  3. Blader, Schooler, Jensen, Pliszka, Kafantaris (2009): Adjunctive divalproex versus placebo for children with ADHD and aggression refractory to stimulant monotherapy. Am J Psychiatry. 2009 Dec;166(12):1392-401. doi: 10.1176/appi.ajp.2009.09020233. PMID: 19884222; PMCID: PMC2940237.

  4. Grondhuis, Farmer, Arnold, Gadow, Findling, Molina, Kolko, Buchan-Page, Rice, Butter, Aman (2019): Standardized Observation Analogue Procedure in the Treatment of Severe Childhood Aggression Study. J Child Adolesc Psychopharmacol. 2019 Nov 15. doi: 10.1089/cap.2019.0109.

  5. Baweja, Waxmonsky (2022): Updates in Pharmacologic Strategies for Emotional Dysregulation in Attention Deficit Hyperactivity Disorder. Child Adolesc Psychiatr Clin N Am. 2022 Jul;31(3):479-498. doi: 10.1016/j.chc.2022.02.003. PMID: 35697397. REVIEW

  6. 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

  7. Kehr, Nöldner, Yoshitake (2006): Effects of chronic administration of Ginkgo biloba extract (EGb 761) on levels of dopamine, noradrenaline and serotonin in the prefrontal cortex of the awake rat; Planta Med 2006; 72 – P_347 DOI: 10.1055/s-2006-950147

  8. Zhou, Han, Wang, Yuan, Sun, You, Song (2017): [Effect of baicalin on behavioral characteristics of rats with attention deficit hyperactivity disorder]. [Article in Chinese]; Zhongguo Dang Dai Er Ke Za Zhi. 2017 Aug;19(8):930-937

  9. Zhou, Han, Wang, Sun (2015): Baicalin may have a therapeutic effect in attention deficit hyperactivity disorder. Med Hypotheses. 2015 Dec;85(6):761-4.

  10. Zhou, Han, Wang, Yuan, Sun, You, Song (2017): [Effect of baicalin on behavioral characteristics of rats with attention deficit hyperactivity disorder]. Zhongguo Dang Dai Er Ke Za Zhi. 2017 Aug;19(8):930-937. Chinese. doi: 10.7499/j.issn.1008-8830.2017.08.016. PMID: 28774371; PMCID: PMC7390057.

  11. Zhou, Wang, Han, Ma, Yuan, Song (2019): Baicalin regulates the dopamine system to control the core symptoms of ADHD. Mol Brain. 2019 Feb 8;12(1):11. doi: 10.1186/s13041-019-0428-5. PMID: 30736828; PMCID: PMC6368814.

  12. Zhou, Wang, You, Sun, Song, Yuan, Han /2019): [Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder]. Zhongguo Dang Dai Er Ke Za Zhi. 2017 May;19(5):576-582. Chinese. doi: 10.7499/j.issn.1008-8830.2017.05.020. PMID: 28506353; PMCID: PMC7389122.

  13. Oehler (2009), Vortrag beim 4. ADHS-Gipfel in Hamburg, 06.-08.02.2009

  14. Dela Peña, Shen, Shi (2021): Droxidopa alters dopamine neuron and prefrontal cortex activity and improves attention-deficit/hyperactivity disorder-like behaviors in rats. Eur J Pharmacol. 2021 Feb 5;892:173826. doi: 10.1016/j.ejphar.2020.173826. PMID: 33347825.

  15. Edel, Vollmoeller (2006): Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung bei Erwachsenen, Springer, Seite 57

  16. Pemolin bei Wikipedia

  17. Weber, Wünsch (2017): Sigma-Rezeptor – Das unbekannte Target; Pharmazeutische Zeitung, Ausgabe 05/2017, 30.01.2017

  18. Moore, Saadabadi (2018): Selegiline. SourceStatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018-2018 Aug 30.