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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 massive aggression. Positive effects have been reported in cases of comorbid aggression in addition to ADHD.45

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

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

1.4. Baikal

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

Baikalin, like MPH, appears to be able to regulate motor skills as well as learning and memory abilities in SHR rats (animal model of ADHD-C), thereby improving the core symptoms of ADHD-C, 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 ADHD through

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

The authors of all available sources seem to be the same persons 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 medication 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. Pemoline)

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

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 symptoms16

Use of sertraline as an ADHD medication little known.

2.2. Axura / Ebixa

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

As ADHD medications, they are hardly used.

2.3. 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.16

2.4. Brexpiprazole

A study of brexpiprazole use in stimulant nonresponders 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.