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MPH Part 4: Miscellaneous, preparations

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MPH Part 4: Miscellaneous, preparations

15. Long-term effects: No habituation effects with MPH

A study of ADHD sufferers taking MPH for 2 years showed a marked worsening of hyperactivity and inattention on discontinuation of MPH, consistent with a recurrence of symptoms improved by MPH.1
A placebo-controlled discontinuation trial in sufferers who had taken MPH for more than 2 years showed that discontinuation of MPH caused a significant increase in ADHD symptoms.2 Nevertheless, after some time, continuation of medication seems to be dispensable in individual sufferers, which justifies regular discontinuation trials.

A meta-analysis of 87 randomized placebo-controlled double-blind trials found no evidence of diminishing effects of methylphenidate, amphetamine medications, atomoxetine, or α2-antagonists with prolonged use.3

16. Gender differences of MPH

One study observed a higher increase in dopamine in the ventral striatum (including the nucleus accumbens) in women than in men. The increase in the dorsal striatum was the same.4

17. Areas of use of methylphenidate in relation to other ADHD medications

  • According to the current European consensus, methylphenidate is the ADHD drug of first choice in children (before amphetamine drugs) and the drug of second choice in adults (after amphetamine drugs)56
  • For children who are MPH nonresponders, that is, who do not respond to MPH, test the efficacy of amphetamine medications.
  • Affected individuals with marked dysphoria with inactivity or with comorbid depression particularly benefit from amphetamine medications.
  • Along with this, sufferers who need more activation may do better with amphetamine medications.
  • Highly gifted individuals are reported to respond better to amphetamine medications than to MPH.7

18. Methylphenidate in other disorders

MPH proved helpful in treating attention problems in children with brain injuries (traumatic brain injury).8

MPH is also used successfully in the treatment of narcolepsy. In 2007, Ritalin® was the only MPH preparation approved for the treatment of narcolepsy.9

In children with ASD, MPH appears to additionally increase cognitive processing speed, unlike in ADHD.10

19. Taking methylphenidate abroad

Taking methylphenidate abroad is possible under certain conditions.

Schengen countries:
A medical certificate is required here, which must be countersigned by the head of the health department.

Other states, USA:
Special provisions apply here.

Muslim countries in particular have draconian penalties for drug possession. This may include stimulants and amphetamine drugs.11

20. MPH medication significantly reduces risk of addiction

The updated 2018 European consensus on the diagnosis and treatment of ADHD concludes that stimulants significantly reduce the risk of addiction while they are taken.12
ADHD sufferers with comorbid cocaine addiction showed a significant reduction in addictive behavior when treated with stimulants. This corresponded to the decrease in ADHD symptoms.13
The international consensus on screening, diagnosis, and treatment of adults with addiction and ADHD recommends treatment with long-acting stimulants at increasing doses to high doses, in combination with psychotherapeutic treatment.14
A meta-analysis of 6 studies with n = 1,014 subjects showed a significantly reduced risk of later addiction for participants medicated with stimulants (here: MPH).15 According to this analysis, the risk of later addiction, whether to alcohol or other substances, is 1.9-fold lower, i.e. almost halved.16

These findings could be supported by the fact that adolescents with marked novelty-seeking who were found to have reduced decreased BOLD activity in mesolimbic (nucleus accumbens (ventral striatum) and midbrain) and prefrontal cortical (dlPFC) regions during reward anticipation at age 14 were more likely to engage in problematic drug use at age 16.17 This could be interpreted to mean that ADHD medications such as MPH or amphetamine medications, which raise dopamine and norepinephrine levels, contribute in a direct way to reduce the risk of addiction.

ADHD medication reduced the influence of preference for short-term rewards and frustration intolerance on Internet addiction.18

One study found no increased addiction affinity in adult rodents from treatment with MPH in youth.19 Other studies also found evidence that stimulants do not increase the risk of addiction.20

21. Methylphenidate preparations

There are a large number of methylphenidate preparations.

Although they all contain the same active ingredient, those affected respond to them differently from person to person. Individual means that some people tolerate preparation A very well and it works well, while preparation B hardly works at all and shows unpleasant side effects, while for others the effect is exactly the opposite.21

A solid MPH drug regimen should therefore always include taking different preparations, even if one preparation is already effective and has no unpleasant side effects. Because whether another preparation does not work even significantly better, can only be determined after its testing.

Depending on the preparation, a high-fat food intake before / during ingestion may delay or accelerate the maximum effect and attenuate or increase the intensity of the effect.21 We do not have any concrete data on this for the preparations available in Europe.

21.1. Unretarded preparations

  • In general:
    • Onset of action after 10 to 20 minutes22
    • Peak effect after 60 minutes
      • Delayed maximum effect when taken with / on a high-fat meal21
    • Duration of action 2.5 - 4 hours
    • If taken twice, maximum of the 2nd intake is higher than that of the first intake23
    • Half-life after 2.9 hours on average (2 to 4 hours)21
  • Preparations
    • Ritalin
      • 1-3 hours effective time
    • Methylphenidate HEXAL
      • 1-3 hours effective time
    • Methylpheni TAD unretarded
      • 1-3 hours effective time
    • Medikinet unretarded
      • 1-3 hours effective time

21.2. Retarded preparations

21.2.1. Half-day dosage

21.2.1.1. Two-phase retardation
  • Equasym Retard/XL
    • Duration until onset of action: 30 minutes22
    • Duration of action (6-)8 hours,22 8 hours24
    • Impact Profile:
      • First maximum after 45 minutes, remains at this level until 2nd maximum23
        Active level higher here than with Concerta
      • Second maximum after 5 hours23
        only slightly increased compared to morning plateau
    • No food intake required before / during ingestion
    • Capsule may be opened22
  • Medikinet Adult
    • Must be taken with food
    • Also approved for adults
    • 6-8 hours22
    • Food intake required before / during ingestion22
    • Bioequivalent to Medikinet Retard25
  • Medikinet Retard
    • Must be taken with food
    • Bioequivalent to Medikinet Adult25
    • Gluten free
    • Contains lactose
    • Duration until onset of action: 30 minutes22
    • Duration of action 6(-8) hours22
    • Impact Profile:23
      • Maximum after 2.5 hours
      • Then drop until after 4 hours
      • Plateau from hour 4 to hour 6 (lower than maximum)
      • Thereafter waste to the end of action
    • Food intake required before / during ingestion22
    • Capsule may be opened22
  • Ritalin LA
    • Bioequivalent to Ritalin Adult
    • Duration of action: 8 hours226-8 hours21
    • Impact Profile:23
      • 50% immediate effect due to beads in capsule21
        • First maximum after 2 hours
        • After that slight drop
      • 50% retarded by beads in capsule21
        • Second maximum after 6 1/2 hours
        • Thereafter waste until active
    • No food intake required before / during ingestion22
    • Delayed maximum effect when taken with / on a high-fat meal21
    • Capsule may be opened and sprinkled on food2221
  • Ritalin Adult
    • Bioequivalent to Ritalin LA25
    • No food intake required before / during ingestion
    • Also approved for adults
    • 8 hours effective time according to manufacturer22
    • Gluten free
    • Contains lactose
  • Methysym
    • Since 01.06.2021 in D
    • 30 % immediate release, 70 % sustained release
    • 10, 20, 30, 40, 50, 60 mg
    • Up to 8 hours effective time
    • No food intake required for ingestion
21.2.1.2. Continuous release
  • Ritalin SR
    • 5-8 hours effective time theoretically, 3-5 hours effective time practically21
    • Continuous release of active ingredient from wax matrix21
    • Half-life after 3.4 hours21

21.2.2. All-day retardation

  • Concerta
    • Bioequivalent to methylphenidate hydrochloride-neuraxpharm

    • Duration until onset of action: 60 minutes22
      Therefore, often good effect with simultaneous intake of small dose of unretarded MPHs

      • Ingestion with / after food may delay maximum effect (Tmax) by up to 1 hour and reduce by 10 to 30% (serum concentration maximum, Cmax)21
    • Duration of action 8-12 hours,22 10-12 hours21

    • Impact Profile:

      • 22 % Immediate effect of the coating21
        • First maximum after 1 hour21 (up to 2 hours) (low), stays at this level until 2nd maximum
      • 78 % retarded by osmotic mechanism21
        • Second maximum after 6 (to 8) hours (significantly higher),22 6.8 hours21
      • Half-life after 3.4 hours21
    • No food intake required before / during ingestion22

    • Capsule must not be opened2221

  • Methylphenidate hydrochloride-neuraxpharm
    • 12 hours effective time
    • Bioequivalent to Concerta
  • Kinecteen
    • 12 hours effective time
    • No food intake required before / during ingestion
  • Methylphenidate hydrochloride Ratiopharm26
    • 12 hours effective time
  • Methylphenidate hydrochloride Hexal27
    • 12 hours effective time

The course of the effect curve differs considerably depending on the MPH preparation. ADHSpedia shows a graph comparing different efficacy curves.28

22. Different MPH preparations have different individual effects - despite identical active ingredient

So far not scientifically substantiated, but empirically recognized beyond doubt, is the fact that methylphenidate preparations can have very different effects in different individuals.29 We suspect a connection with the different effect (time) profiles and different fillers.
We know sufferers who reacted to one MPH preparation with aggression and responded quite excellently to another preparation - and other sufferers who reacted to the two preparations with exactly the opposite reactions.
The phenomenon is widely known in sufferer forums and testing of various MPH preparations is regularly recommended by sufferers among themselves.

Among adults, however, methylphenidate is being replaced more and more by Elvanse since the approval of Elvanse Adult in May 2019. among adults, amphetamine medications are the drug of choice over methylphenidate.

A graph illustrates the active ingredient profile of

  • Concerta
  • Ritalin Adult / LA
  • Medikinet adult
  • MPH unretarded

https://www.pharmazeutische-zeitung.de/fileadmin/_processed_/1/1/csm_15489_d3da8723e2.jpg 30

23. Further sources on methylphenidate

A detailed graphical and explanatory account of the pathway of action of methylphenidate can be found at www.pharmgkb.org.31 Another comprehensive account of methylphenidate can be found at drugbank.com.32


  1. Matthijssen, Dietrich, Bierens, Kleine Deters, van de Loo-Neus, van den Hoofdakker, Buitelaar, Hoekstra (2019): Effects of Discontinuing Methylphenidate on Strengths and Difficulties, Quality of Life and Parenting Stress. J Child Adolesc Psychopharmacol. 2019 Dec 24. doi: 10.1089/cap.2019.0147.

  2. Matthijssen, Dietrich, Bierens, Kleine Deters, van de Loo-Neus, van den Hoofdakker, Buitelaar, Hoekstra (2019): Continued Benefits of Methylphenidate in ADHD After 2 Years in Clinical Practice: A Randomized Placebo-Controlled Discontinuation Study. Am J Psychiatry. 2019 Sep 1;176(9):754-762. doi: 10.1176/appi.ajp.2019.18111296.

  3. Castells, Ramon, Cunill, Olivé, Serrano (2020): Relationship Between Treatment Duration and Efficacy of Pharmacological Treatment for ADHD: A Meta-Analysis and Meta-Regression of 87 Randomized Controlled Clinical Trials. J Atten Disord. 2020 Feb 20:1087054720903372. doi: 10.1177/1087054720903372. PMID: 32075485.

  4. Manza, Shokri-Kojori, Wiers, Kroll, Feldman, McPherson, Biesecker, Dennis, Johnson, Kelleher, Qu, Tomasi, Wang, Volkow (2021): Sex differences in methylphenidate-induced dopamine increases in ventral striatum. Mol Psychiatry. 2021 Oct 27. doi: 10.1038/s41380-021-01294-9. Epub ahead of print. PMID: 34707237. n = 95

  5. Kooij, Bijlenga, Salerno, Jaeschke, Bitter, Balázs, Thome, Dom, Kasper, Filipe, Stes, Mohr, Leppämäki, Brugué, Bobes, Mccarthy, Richarte, Philipsen, Pehlivanidis, Niemela, Styr, Semerci, Bolea-Alamanac, Edvinsson, Baeyens, Wynchank, Sobanski, Philipsen, McNicholas, Caci, Mihailescu, Manor, Dobrescu, Krause, Fayyad, Ramos-Quiroga, Foeken, Rad, Adamou, Ohlmeier, Fitzgerald, Gill, Lensing, Mukaddes, Brudkiewicz, Gustafsson, Tania, Oswald, Carpentier, De Rossi, Delorme, Simoska, Pallanti, Young, Bejerot, Lehtonen, Kustow, Müller-Sedgwick, Hirvikoski, Pironti, Ginsberg, Félegeházy, Garcia-Portilla, Asherson (2018): Updated European Consensus Statement on diagnosis and treatment of adult ADHD, European Psychiatrie, European Psychiatry 56 (2019) 14–34, http://dx.doi.org/10.1016/j.eurpsy.2018.11.001, Seite 22, 7.4.1.

  6. Cortese, Adamo, Del Giovane, Mohr-Jensen, Hayes, Carucci, Atkinson, Tessari, Banaschewski, Coghill, Hollis, Simonoff, Zuddas, Barbui, Purgato, Steinhausen, Shokraneh, Xia, Cipriani (2018): Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2018 Sep;5(9):727-738. doi: 10.1016/S2215-0366(18)30269-4. REVIEW

  7. Castello et al. 1992, zitiert nach Arnold: Journal of Attention Disorders Vol. 3(4):200-211 (2000) Methylphenidate vs. amphetamine: Comparative review. REVIEW

  8. LeBlond, Smith-Paine, Riemersma, Horn, Wade, Kurowski (2019): Influence of Methylphenidate on Long-Term Neuropsychological and Everyday Executive Functioning After Traumatic Brain Injury in Children with Secondary Attention Problems. J Int Neuropsychol Soc. 2019 Jun 10:1-10. doi: 10.1017/S1355617719000444.

  9. Handwerker (2007): Narkolepsie. Monatsschrift Kinderheilkunde. July 2007, Volume 155, Issue 7, pp 624–629

  10. Peled, Cassuto, Berger (2019): Processing speed as a marker to stimulant effect in clinical sample of children with high functioning autism spectrum disorder. Nord J Psychiatry. 2019 Nov 5:1-5. doi: 10.1080/08039488.2019.1686063.

  11. http://www.ads-hyperaktivitaet.de/FAQ/Infos/Medis/medis.html#1

  12. Kooij, Bijlenga, Salerno, Jaeschke, Bitter, Balázs, Thome, Dom, Kasper, Filipe, Stes, Mohr, Leppämäki, Brugué, Bobes, Mccarthy, Richarte, Philipsen, Pehlivanidis, Niemela, Styr, Semerci, Bolea-Alamanac, Edvinsson, Baeyens, Wynchank, Sobanski, Philipsen, McNicholas, Caci, Mihailescu, Manor, Dobrescu, Krause, Fayyad, Ramos-Quiroga, Foeken, Rad, Adamou, Ohlmeier, Fitzgerald, Gill, Lensing, Mukaddes, Brudkiewicz, Gustafsson, Tania, Oswald, Carpentier, De Rossi, Delorme, Simoska, Pallanti, Young, Bejerot, Lehtonen, Kustow, Müller-Sedgwick, Hirvikoski, Pironti, Ginsberg, Félegeházy, Garcia-Portilla, Asherson (2018): Updated European Consensus Statement on diagnosis and treatment of adult ADHD, European Psychiatrie, European Psychiatry 56 (2019) 14–34, http://dx.doi.org/10.1016/j.eurpsy.2018.11.001, Seite 22, 7.4.4.

  13. Manni, Cipollone, Pallucchini, Maremmani, Perugi, Maremmani (2019): Remarkable Reduction of Cocaine Use in Dual Disorder (Adult Attention Deficit Hyperactive Disorder/Cocaine Use Disorder) Patients Treated with Medications for ADHD. Int J Environ Res Public Health. 2019 Oct 15;16(20). pii: E3911. doi: 10.3390/ijerph16203911.

  14. Crunelle, van den Brink, Schellekens, van de Glind, Icasa Consortium, Matthys (2019): [International consensus for the screening, diagnosis and treatment of adult patients with substance use disorder and ADHD]. [Article in Dutch] Tijdschr Psychiatr. 2019;61(7):477-487.

  15. 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. REVIEW

  16. Edel, Vollmoeller (2006): Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung bei Erwachsenen, Springer, Seite 120

  17. Büchel, Peters, Banaschewski, Bokde, Bromberg, Conrod, Flor, Papadopoulos, Garavan, Gowland, Heinz, Walter, Ittermann, Mann, Martinot, Paillère-Martinot, Nees, Paus, Pausova, Poustka, Rietschel, Robbins, Smolka, Gallinat, Schumann, Knutson, the IMAGEN consortium (2012): Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents; Nat Commun. 2017; 8: 14140. doi: 10.1038/ncomms14140; PMCID: PMC5321762; n = 144

  18. Lu, Chou, Hsiao, Hu, Yen (2019): Correlations of Internet Addiction Severity With Reinforcement Sensitivity and Frustration Intolerance in Adolescents With Attention-Deficit/Hyperactivity Disorder: The Moderating Effect of Medications. Front Psychiatry. 2019 Apr 26;10:268. doi: 10.3389/fpsyt.2019.00268. eCollection 2019.

  19. Zhang-James, Lloyd, James, Yang, Richards, Faraone (2019); Oral Methylphenidate Treatment of an Adolescent ADHD Rat Model Does Not Alter Cocaine-Conditioned Place Preference during Adulthood: A Negative Report. J Psychiatr Brain Sci. 2019;4. pii: e190021. doi: 10.20900/jpbs.20190021.

  20. Ide, Ikekubo, Hua, Takamatsu, Uhl, Sora, Ikeda (2018): Reward-enhancing effect of methylphenidate is abolished in dopamine transporter knockout mice: A model of attention-deficit/hyperactivity disorder. Neuropsychopharmacol Rep. 2018 Sep;38(3):149-153. doi: 10.1002/npr2.12020.

  21. Elbe, Black, McGrane, Procyshyn (Hrsg.) (2019): Clinical Handbook of Psychotrophic Drugs for Children and Adolescents, 4th edition

  22. https://www.kinderaerzte-im-netz.de/media/53ec94e833af614b730097d1/source/20080530092715_adhs2.pdf

  23. Banaschewski, Coghill, Santosh, Zuddas, Asherson, Buitelaar, Danckaerts, Döpfner, Faraone, Rothenberger, Sergeant, Steinhausen, Sonuga-Barke, Taylor (2006): Long-acting medications for the hyperkinetic disorders; A systematic review and European treatment guideline; Eur Child Adolesc Psychiatry. 2006 Dec;15(8):476-95. REVIEW

  24. Medikamenteninformation des Herstellers Shire

  25. https://www.adhspedia.de/wiki/Medikamente

  26. Medikamenten-Fachinformation des Herstellers ratiopharm

  27. Fachinformation Gelbe Liste Methylphenidathydrochlorid Hexal

  28. https://www.adhspedia.de/wiki/Ritalin_Adult

  29. Schonwald, Chan, Nyp (2019): Not Really “The Same Thing”. J Dev Behav Pediatr. 2019 Dec 3. doi: 10.1097/DBP.0000000000000756.

  30. Lenhart (2019): ADHS – Bei Erwachsenen häufig unterschätzt. Pharmazeutische Zeitung

  31. pharmgkb.org: Methylphenidate Pathway, Pharmacodynamics. Abruf 26.03.22

  32. Drugbank: Methylphenidate. Abgerufen 30.03.2022