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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 primarily dopaminergic drugs

1.1. Risperidone

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

Risperidone blocks the dopamine D2 receptor (although only 1/3 in comparison to haloperidol (brand: Haldol)) and therefore has an antipsychotic effect.

A placebo-controlled study of the efficacy of risperidone or divalproex sodium in children with ADHD on residual aggressive behavior following stimulant optimization. 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 obviate the need for additional medication. If this did not already result in symptom remission of aggressive behavior, risperidone and divalproex sodium were effective adjunctive therapies. Risperidone was associated with weight gain.2 Another study on divalproex came to similar conclusions.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 alongside ADHD.45

For the problem of blocking D2 receptors in ADHD, see ⇒ General information on antipsychotics as D2 antagonists in ADHD.

Risperidone is certainly not suitable for the classic medication of ADHD (without inferiority or aggressiveness).

1.2. Isoproterenol / Isoprenaline

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

Hardly known for use as an ADHD medication.

1.3. Gingko extract EGb 761

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

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

It should not be used as a medication for ADHD before further studies are carried out, especially as the study was apparently not published in a specialist journal, which indicates that no rigorous review process, as is usual for specialist journals, was carried out.

1.4. Baikal

Studies address a reduction of hyperactivity symptoms by baikalin in rats.89

Baikalin, like MPH, appears to be able to regulate the motor skills as well as the learning and memory skills of SHR rats (animal model of ADHD-C) and thus improve the core symptoms of ADHD-C, i.e. hyperactivity, impulsive behavior and inattention. Baikalin has a dose-dependent effect. Compared to MPH, it takes longer to develop its therapeutic effect.10

Baikalin could have a therapeutic effect on ADHD through

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

The authors of all available sources appear to be the same persons or the same main author. Publications by other authors on Baikalin for ADHD were not found. Before verification by several different author teams and testing 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 substance that is metabolized by the body to amphetamine. Mentioned as an ADHD medication, but completely uncommon and hardly documented.13

(1.6. Pemolin)

Pemoline is said to have had a comparable effect to MPH.1415

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

Former trade names: Cylert, Stimul, Tradon

2. Other medications with primarily other modes of action

2.1. Sertraline

  • Predominantly serotonergic effect.
  • Sigma-1 antagonist
    • Worsens psychotic symptoms16

The use of sertraline as an ADHD medication is hardly known.

2.2. Axura / Ebixa

Axura / Ebixa are dementia drugs.
They are predominantly glutamatergic.

They are rarely used as ADHD medications.

2.3. Opipramol

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

Opipramol binds strongly to sigma-1 and sigma-2 receptors, but does not inhibit the reuptake of biogenic amines like conventional TCAs. Subtherapeutic doses reduce the sigma-2 receptor density.16

2.4. Brexpiprazole

A study on the use of brexpiprazole in stimulant non-responders found no significant improvement in ADHD symptoms.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. Edel, Vollmoeller (2006): Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung bei Erwachsenen, Springer, Seite 57

  15. Pemolin bei Wikipedia

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

  17. Reimherr, Gift, Steans, Reimherr, Rosenberg, Wilson, Marchant (2022): The Use of Brexpiprazole Combined With a Stimulant in Adults With Treatment-Resistant Attention-Deficit/Hyperactivity Disorder. J Clin Psychopharmacol. 2022 Aug 17. doi: 10.1097/JCP.0000000000001592. PMID: 35977005.