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Choice of medication for ADHD


Choice of medication for ADHD

“Treating ADHD is easy. Treating ADHD well is very difficult.”

Choosing the most effective medication for ADHD and dosing it optimally is a challenge. There are, to be sure, quite a few points of reference for orientation. Often enough, however, the individual characteristics of each sufferer put all empirical values to the test. Since there is no such thing as “one ADHD”, but rather ADHD symptoms can arise from a large number of different causes, a large number of different options must be tried out for each affected person if necessary.

1. Advantages and disadvantages of different ADHD medications

1.1. Stimulants

  • Benefits (common benefits of stimulants)
  • Disadvantages (common disadvantages of stimulants
    • Impairment of emotional sensation in approximately 20% of affected individuals due to the depressant effect of stimulants on the limbic system
      • Causes: Hypersensitivity or overdose
      • In this case, consider combination medication of 50% atomoxetine and 50% MPH or AMP (each compared to monotherapy)
  • Methylphenidate (MPH)
    • Advantages:
      • Particularly good drive increase
      • Unretarded short duration of action (2.5 - 3 hours)
    • Disadvantages:
      • Nonresponder rate approx. 30
        • MPH nonresponding not congruent with AMP nonresponding
  • Amphetamine drugs (AMP)
    • Advantages
      • More mood-equalizing than MPH
    • Disadvantages:
      • Nonresponder rate approx. 20
        • AMP nonresponding not congruent with MPH nonresponding

1.2. Nonstimulants

  • Atomoxetine (ATX)
    • Advantages
      • Mirror drug
      • No impairment of emotional sensation, as no dampening effect on the limbic system
    • Disadvantages
      • Difficult to dose
      • Sometimes very narrow range between under- and overdosing
      • Considerably higher side effects than stimulants
      • Lower effect strength than stimulants
  • Guanfacin
    • Advantages
      • Good effect in comorbid tic disorders
      • Antihypertensive - helpful in case of high blood pressure
    • Disadvantages
      • Has little effect on adults
      • Higher side effects than stimulants
      • Lower effect strength than stimulants

2. Drug selection according to specific problem cases

The following is the beginning of a collection and is still quite incomplete.

2.1. MPH Nonresponder

  • Adults: AMP, then atomoxetine, then guanfacine
  • Children: AMP, then guanfacine, then atomoxetine, then guanfacine

2.2. Amphetamine medication nonresponder

  • Adults: MPH, then atomoxetine, then guanfacine
  • Children: MPH, then guanfacine, then atomoxetine, then guanfacine

2.3. Emotional impairment due to stimulants

  • Reduce stimulants
    • Stimulants inhibit the limbic system.
      In sensitive sufferers, this can be too strong and cause an emotional flattening (“zombies”). This is not a normal reaction.
      Here, it should first be ensured that this does not result from an overdose. Therefore, the stimulants should be dosed down first, and if necessary, much more finely than the standard doses of the drugs provide. The next options should be considered only after it has been ensured that a dosage reduction that just misses the emotional impairment does not sufficiently improve ADHD symptoms.
  • Atomoxetine or guanfacine instead of stimulants
    • Nonstimulants
      • Do not inhibit the limbic system
      • Do not improve drive
  • Combination medication (advantage: drive from stimulants remains, emotional dysregulation is improved throughout the day)
    • Adults: stimulants and atomoxetine
    • Children: stimulants and guanfacine or stimulants and atomoxetine

2.4. Inhibition / impulse control control

The ADHD symptom of lack of inhibition of executive functions is caused dopaminergically by the basal ganglia (striatum, putamen)1

  • Lack of inhibition of emotion regulation is noradrenergically caused by the hippocampus.1
  • Thus, the former is likely to be more amenable to dopaminergic treatment, whereas emotion regulation and affect control are likely to be more amenable to noradrenergic treatment.


  • Impulsivity is also serotonergically mediated
  • If strong impulsivity is a prominent ADHD symptom, it would be negligent to use stimulants at such high doses that this is adequately eliminated, since this would result in an overdose with regard to the other symptoms
  • Serotonin reuptake inhibitor
    • Significantly lower doses than when used as antidepressants
    • E.g.:
      • (Es)Citalopram 2-4 mg / day
      • Imipramine 10 mg / day

2.5. Inattention

In a small placebo-controlled trial, selegiline improved only inattention but not hyperactivity/impulsivity.2

2.6. Anxiety disorder comorbid

Atomoxetine may help reduce comorbid anxiety symptoms in children and adolescents.3

2.7. Tic disorders comorbid

  • Guanfacin4
  • Atomoxetine4
  • Selegiline5

2.8. ASA comorbid

  • MPH: worse effect on hyperactivity in intellectual impairment6
  • Atomoxetine: worse effect on ADHD symptoms with the same level of tolerability6
  • Guanfacine: same effect on hyperactivity in intellectual impairment, with poorer tolerance6

2.9. Stimulant weight loss

Stimulants and desipramine are often associated with the side effect of decreased appetite and consequent weight loss.
Nortryptiline is reported to be associated with weight gain as a side effect7

Augmenting administration of low doses of antipsychotics could help prevent stimulant-induced weight loss.
While MPH was often associated with appetite deficiency, thioridazine showed an increase in appetite as a side effect.8 Atypical antipsychotics are reported to show an even stronger effect toward appetite increase and metabolic syndrome.9

Combination treatment with antipsychotics and psychostimulants is being used more and more frequently. 10 Improved efficacy compared to stimulant monotherapy has also been reported in isolated cases.9 One registry study found that 3.9% of ADHD children and adolescents receiving stimulants were comedicated with atypical antipsychotics.11

This opens up the option of using combination medication to counteract excessive weight loss with stimulants.

2.10. Depression comorbid

In ADHD with mild comorbid depression, monotherapy with stimulants should be given first.
In about one-third of all treatment-resistant depression, previously undiagnosed ADHD is found.
Given the rapid effectiveness of stimulants, it should be observed whether the elimination of the ADHD problem eliminates the stressor driving the depression. This is quite often the case.
A study of comedication of stimulants and MAO inhibitors in depression found no problems arising in the process,12 contrary to the commonly assumed problem of hypertensive crises.
Another study reported successful comedication of selegiline and lisdexamfetamine (Vyvanse) for ADHD and comorbid depression13
Thus, combination medication of selegiline with stimulants may also be considered for ADHD.

2.11. Aggression comorbid

Several atypical antipsychotics, particularly risperidone, effectively ameliorated aggression. Some studies showed, contrary to FDA warnings that stimulants could worsen aggression, that stimulants, like antipsychotics, were effective in improving aggression, especially in hyperactive children14

Combination treatment with (low-dose) antipsychotics and psychostimulants may be helpful, especially in cases of comorbid aggression, when monotherapy with stimulants and a combination of stimulants with behavioral interventions have not been sufficient to treat aggression.10 Several expert panels concluded that when aggression comorbid to ADHD (not: aggression following from stimulants) is not sufficiently ameliorated by stimulant prescription, concomitant use of atypical antipsychotics is indicated, with cautious dosing.1516

For comedication of antipsychotics and psychostimulants, see also weight loss above.

3. Different modes of action of ADHD medications

3.1. Binding affinity of MPH, AMP, ATX to DAT / NET / SERT

The active ingredients methylphenidate (MPH), d-amphetamine (d-AMP), l-amphetamine (l-AMP) and atomoxetine (ATX) bind with different affinities to dopamine transporters (DAT), noradrenaline transporters (NET) and serotonin transporters (SERT). The binding causes inhibition of the activity of the respective transporters.17

Binding affinity: stronger with smaller number (KD = Ki) DAT NET SERT
MPH 34 - 200 339 > 10,000
d-AMP (Elvanse, Attentin) 34 - 41 23.3 - 38.9 3,830 - 11,000
l-AMP 138 30.1 57,000
ATX 1451 - 1600 2.6 - 5 48 - 77

3.2. Effect of MPH, AMP, ATX on dopamine / norepinephrine per brain region

The drugs methylphenidate (MPH), d-amphetamine (AMP), and atomoxetine (ATX) differentially alter extracellular dopamine (DA) and norepinephrine (NE) in different brain regions. Table based on Madras,17 modified.

PFC striatum nucleus accumbens cortex occipital hypothalamus lateral hippocampus dorsal cerebellum
NE (+)
DA +
NE +/- 0
DA +
NE +/- 0
NE +
DA +
NE +/- 0
DA +
NE +/- 0
NE +
DA +/- 0
NE +/- 0
DA +/- 0
NE +/- 0
DA +/- 0
NE + (rat)
DA +/- 0
NE + (rat)
DA +/- 0
NE + (rat)
DA +/- 0
NE + (rat)

Note: the NET binds dopamine slightly better than norepinephrine, the DAT binds dopamine much better than norepinephrine.
Nevertheless, atomoxetine increases dopamine only in the PFC and not everywhere it binds to the NET, so there appears to be a specific mechanism of action here.

4. Duration of action of various ADHD drugs

See also Medication duration in ADHD

  1. Müller, Candrian, Kropotov (2011): ADHS – Neurodiagnostik in der Praxis, Seite 85

  2. Rubinstein, Malone, Roberts, Logan (2006): Placebo-controlled study examining effects of selegiline in children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2006 Aug;16(4):404-15. doi: 10.1089/cap.2006.16.404. PMID: 16958566. n = 11

  3. Khoodoruth, Ouanes, Khan (2022): A systematic review of the use of atomoxetine for management of comorbid anxiety disorders in children and adolescents with attention-deficit hyperactivity disorder. Res Dev Disabil. 2022 Jun 9;128:104275. doi: 10.1016/j.ridd.2022.104275. PMID: 35691145. REVIEW

  4. Jaffe, Coffey (2022): Pharmacologic Treatment of Comorbid Attention-Deficit/Hyperactivity Disorder and Tourette and Tic Disorders. Child Adolesc Psychiatr Clin N Am. 2022 Jul;31(3):469-477. doi: 10.1016/j.chc.2022.03.004. Epub 2022 May 11. PMID: 35697396. REVIEW

  5. Jankovic J. Deprenyl in attention deficit associated with Tourette’s syndrome. Arch Neurol. 1993 Mar;50(3):286-8. doi: 10.1001/archneur.1993.00540030052014. PMID: 8442708. n = 29

  6. Joshi, Wilens (2022): Pharmacotherapy of Attention-Deficit/Hyperactivity Disorder in Individuals with Autism Spectrum Disorder. Child Adolesc Psychiatr Clin N Am. 2022 Jul;31(3):449-468. doi: 10.1016/j.chc.2022.03.012. PMID: 35697395. REVIEW

  7. Otasowie, Castells, Ehimare, Smith (2014): Tricyclic antidepressants for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev. 2014 Sep 19;(9):CD006997. doi: 10.1002/14651858.CD006997.pub2. PMID: 25238582., METASTUDY

  8. Gittelman-Klein R, Klein DF, Katz S, Saraf K, Pollack E (1976): Comparative effects of methylphenidate and thioridazine in hyperkinetic children. I. Clinical results. Arch Gen Psychiatry. 1976 Oct;33(10):1217-31. doi: 10.1001/archpsyc.1976.01770100079008. PMID: 971031.

  9. Elbe D, Barr AM, Honer WG, Procyshyn RM (2014): Managing ADHD and disruptive behaviour disorders with combination psychostimulant and antipsychotic treatment. J Psychiatry Neurosci. 2014 May;39(3):E32-3. doi: 10.1503/jpn.130288. PMID: 24758945; PMCID: PMC3997610.

  10. Linton D, Barr AM, Honer WG, Procyshyn RM (2013): Antipsychotic and psychostimulant drug combination therapy in attention deficit/hyperactivity and disruptive behavior disorders: a systematic review of efficacy and tolerability. Curr Psychiatry Rep. 2013 May;15(5):355. doi: 10.1007/s11920-013-0355-6. PMID: 23539465. REVIEW

  11. Bali V, Kamble PS, Aparasu RR (2015): Predictors of concomitant use of antipsychotics and stimulants and its impact on stimulant persistence in pediatric attention deficit hyperactivity disorder. J Manag Care Spec Pharm. 2015 Jun;21(6):486-98. doi: 10.18553/jmcp.2015.21.6.486. PMID: 26011550.

  12. Feinberg (2004): Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication. J Clin Psychiatry. 2004 Nov;65(11):1520-4. doi: 10.4088/jcp.v65n1113. PMID: 15554766.

  13. Israel (2015): Combining Stimulants and Monoamine Oxidase Inhibitors: A Reexamination of the Literature and a Report of a New Treatment Combination. Prim Care Companion CNS Disord. 2015 Dec 10;17(6):10.4088/PCC.15br01836. doi: 10.4088/PCC.15br01836. PMID: 27057401; PMCID: PMC4805402., REVIEW

  14. Yanofski J. The dopamine dilemma: using stimulants and antipsychotics concurrently. Psychiatry (Edgmont). 2010 Jun;7(6):18-23. PMID: 20622942; PMCID: PMC2898838.

  15. Kutcher S, Aman M, Brooks SJ, Buitelaar J, van Daalen E, Fegert J, Findling RL, Fisman S, Greenhill LL, Huss M, Kusumakar V, Pine D, Taylor E, Tyano S (2004): International consensus statement on attention-deficit/hyperactivity disorder (ADHD) and disruptive behaviour disorders (DBDs): clinical implications and treatment practice suggestions. Eur Neuropsychopharmacol. 2004 Jan;14(1):11-28. doi: 10.1016/s0924-977x(03)00045-2. PMID: 14659983.

  16. Pliszka SR, Crismon ML, Hughes CW, Corners CK, Emslie GJ, Jensen PS, McCRACKEN JT, Swanson JM, Lopez M (2006): TEXAS CONSENSUS CONFERENCE PANEL ON PHARMACOTHERAPY OF CHILDHOOD ATTENTION DEFICIT HYPERACTIVITY DISORDER. The Texas Children’s Medication Algorithm Project: revision of the algorithm for pharmacotherapy of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2006 Jun;45(6):642-657. doi: 10.1097/01.chi.0000215326.51175.eb. PMID: 16721314.

  17. Madras, Miller, Fischman (2005): The dopamine transporter and attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005 Jun 1;57(11):1397-409. doi: 10.1016/j.biopsych.2004.10.011. PMID: 15950014.