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Methylphenidate (MPH) for ADHD


Methylphenidate (MPH) for ADHD

Medication for ADHD should only be prescribed after careful diagnosis by specialized medical professionals. This information cannot replace sound medical advice and is intended only to support discussions with doctors and therapists.

Methylphenidate is one of the most important drugs for the treatment of ADHD and is also used to treat narcolepsy and depression. Methylphenidate is a stimulant.

Stimulants have been used for many decades as ADHD medications and, when used as directed, have a high effect strength with few side effects. They also reduce the likelihood of addiction developing,12 in any case they do not increase it.34
Treating ADHD with stimulants as early as possible reduced the risk of developing addiction in adulthood. Each year that stimulant treatment started later increased the risk of addiction development in adulthood by 1.46 times.5

A fundamental distinction must be made between stimulants as medications and stimulants as drugs. A fast, high dosage that occupies the majority of the receptors and quickly decreases again (= drugs) leads to an excess of neurotransmitters and thus triggers states of intoxication. In contrast, a slow, low dosage that only partially occupies the receptors (= drugs) merely compensates for the neurotransmitter deficit that exists in ADHD and eliminates the symptoms triggered by this.

Stimulants act primarily dopaminergic and to a lesser extent noradrenergic as reuptake inhibitors.
Nicotine has an indirect stimulant effect by binding to acetylcholine receptors and thereby indirectly causing a release of (among other things) dopamine.6

Stimulants act dopaminergically on the nucleus accumbens to improve symptoms of hyperactivity and self-activation/reinforcement processes, whereas the problems of response delay and working memory are mediated by noradrenergic effects of the locus coeruleus on the PFC. The effects of stimulants on attention and behavioral control are mediated dopaminergically and noradrenergically.7

Stimulants details

Stimulants (e.g., nicotine, methylphenidate, amphetamines, entactogens, cocaine) enhance dopaminergic neurotransmission in the striatum by increasing dopamine release and/or inhibiting presynaptic dopamine reuptake. Opioidergic substances (e.g., alcohol, cannabis, opioids) act indirectly dopaminergic by means of a μ-opioid receptor mechanism by activating dopaminergic neurons of the VTA and by directly addressing opioid receptors.8
These mechanisms are utilized by any healthy brain through endogenous dopamine, endogenous endorphins and endogenous opioids. Intoxication results from a very rapid (phasic) increase in dopamine in the brain, which can only be brought about by increased dopamine release from the vesicles. Drugs, on the other hand, as reuptake inhibitors via a slow (tonic) increase, do not produce any intoxicating effect, but even indirectly reduce the phasic dopamine level.

Stimulants improve cognitive abilities. In a very large study of n = 766244 subjects, a relevant improvement in test scores of ADHD sufferers under stimulant medication was found, although the performance level of non-affected subjects was not reached. In contrast, selective serotonin reuptake inhibitors had no effect on test scores.9

Methylphenidate for ADHD

Methylphenidate is the first-choice drug in Europe for children and the second-choice drug (after amphetamine drugs) for ADHD in adults. It has been known since 1937.
In the U.S., adolescents with ADHD receive 52.9% MPH and 39.3% amphetamine medications as their first prescribed ADHD medication. Over the course of treatment, MPH is the primary prescribed medication in about 40% and AMP is the primary prescribed medication in 33%.10

  1. Wilens, Kaminski (2019): Editorial: Stimulants: Friend or Foe? J Am Acad Child Adolesc Psychiatry. 2019 Nov 20. pii: S0890-8567(19)32157-4. doi: 10.1016/j.jaac.2019.11.009.

  2. Wilens, Faraone, Biederman, Gunawardene (2003): Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics. 2003 Jan;111(1):179-85. doi: 10.1542/peds.111.1.179. PMID: 12509574. METASTUDY

  3. Humphreys, Eng, Lee (2013): Stimulant medication and substance use outcomes: a meta-analysis. JAMA Psychiatry. 2013 Jul;70(7):740-9. doi: 10.1001/jamapsychiatry.2013.1273. PMID: 23754458; PMCID: PMC6688478. METASTUDY

  4. Molina, Hinshaw, Eugene Arnold, Swanson, Pelham, Hechtman, Hoza, Epstein, Wigal, Abikoff, Greenhill, Jensen, Wells, Vitiello, Gibbons, Howard, Houck, Hur, Lu, Marcus; MTA Cooperative Group. (2013): Adolescent substance use in the multimodal treatment study of attention-deficit/hyperactivity disorder (ADHD) (MTA) as a function of childhood ADHD, random assignment to childhood treatments, and subsequent medication. J Am Acad Child Adolesc Psychiatry. 2013 Mar;52(3):250-63. doi: 10.1016/j.jaac.2012.12.014. PMID: 23452682; PMCID: PMC3589108. n = 697

  5. Dalsgaard, Mortensen, Frydenberg, Thomsen (2014): ADHD, stimulant treatment in childhood and subsequent substance abuse in adulthood – a naturalistic long-term follow-up study. Addict Behav. 2014 Jan;39(1):325-8. doi: 10.1016/j.addbeh.2013.09.002. PMID: 24090624. n = 208


  7. Solanto (1995): Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration; Behav Brain Res. 1998 Jul;94(1):127-52. REVIEW

  8. Edel, Vollmoeller (2006): Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung bei Erwachsenen, Springer, Seite 112

  9. Rohde (2017): Efficacy of Stimulants Beyond Treatment of Core Symptoms of Attention-Deficit/Hyperactivity Disorder; JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.1423

  10. Fouladvand, Hankosky, Bush, Chen, Dwoskin, Freeman, Henderson, Kantak, Talbert, Tao, Zhang (2019): Predicting substance use disorder using long-term attention deficit hyperactivity disorder medication records in Truven. Health Informatics J. 2019 May 19:1460458219844075. doi: 10.1177/1460458219844075.

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