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Modafinil for ADHD


Modafinil for ADHD

Modafinil is a stimulant that has not been subject to narcotics legislation since 2008 and has also been available as a generic since 2012. The molecular structure differs significantly from amphetamines.

Trade names: Provigil (USA), Generic

The regular indication is narcolepsy. It is used off-label for ADHD. In ADHD with comorbid narcolepsy, it is likely to be the first choice of medication.

Even as a generic, modafinil is still disproportionately expensive. Off-label use outside the approved indication of narcolepsy will therefore barely be covered by health insurance companies.

1. Modafinil for ADHD (off label)

As modafinil has been associated with the occurrence of Stevens-Johnsons syndrome, modafinil is not approved for the treatment of ADHD and can therefore only be used off-label.1

There are several reports from people with ADHD in forums about a very positive effect of modafinil, as well as reports from non-responders. Modafinil has a very consistent effect throughout the day with a half-life of 12 to 15 hours and in this respect is superior to most MPH products or amphetamine salts.

Several larger double-blind placebo-controlled studies confirm modafinil’s good efficacy in ADHD.234

A study on adults came to the different conclusion of good tolerability, but found no significant improvements in ADHD symptoms compared to placebo.5

Modafinil has an Effect size of 0.65 in ADHD for both ADHD-I and ADHD-C.6 This corresponds to the value of atomoxetine (Strattera).
Effectiveness of different forms of treatment for ADHD

2. Modafinil pathways of action

The mode of action of modafinil is not yet fully understood. There appears to be a strong dopaminergic component.7
Modafinil is an atypical stimulant and also acts on GABA, glutamates, serotonin and noradrenaline.8

Modafinil apparently increases orexin levels. This could be one of the pathways of action of modafinil in the treatment of narcolepsy.9

Orexin levels appear to be reduced in ADHD-I. More on this at Orexin / hypocretin In this regard, modafinil could find a specific area of application in ADHD-I.

3. Side effects of modafinil

One of the side effects of modafinil is that modafinil increases histamine,10 just like the well-known ADHD medications:

  • Amphetamine drugs
  • Methylphenidate
  • Atomoxetine
  • Nicotine
  • Caffeine

Therefore, people with histamine intolerance often have problems due to taking ADHD medication.
A person with ADHD with histamine intolerance reported that she could not tolerate AMP and sustained release MPH at all, but could tolerate immediate release MPH in small doses.

Another reported side effect is a moderate reduction in appetite.11

  1. Walitza, Romanos, Renner, Gerlach (2016): Psychostimulanzien und andere Arzneistoffe, die zur Behandlung der Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) angewendet werden, S. 291, in; Gerlach, Mehler-Wex, Walitza, Warnke (Hrsg,) (2016): Neuro-/Psychopharmaka im Kindes- und Jugendalter: Grundlagen und Therapie.

  2. Biederman, Pliszka (2008): Modafinil Improves Symptoms of Attention-Deficit/Hyperactivity Disorder across Subtypes in Children and Adolescents; The Journal of Pediatrics, March 2008, Volume 152 , Issue 3 , 394 – 399.e2, n = 638

  3. Swanson, Greenhill, Lopez, Sedillo, Earl, Jiang, Biederman (2006): Modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder: results of a randomized, double-blind, placebo-controlled, fixed-dose study followed by abrupt discontinuation. J Clin Psychiatry. 2006 Jan;67(1):137-47.

  4. Wang, Han, Lee, Jun, Patkar, Masand, Pae (2017): Modafinil for the treatment of attention-deficit/hyperactivity disorder: A meta-analysis. J Psychiatr Res. 2017 Jan;84:292-300. doi: 10.1016/j.jpsychires.2016.09.034.

  5. Arnold, Feifel, Earl, Yang, Adler (2014): A 9-week, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study to evaluate the efficacy and safety of modafinil as treatment for adults with ADHD. J Atten Disord. 2014 Feb;18(2):133-44. doi: 10.1177/1087054712441969. n = 330

  6. Metaanalyse einer hohen Anzahl von Studien durch Taylor (Eric), European guidelines on diagnosis and treatment of ADHD, Vortrag auf dem internationalen Symposium in Achen, 14.03.2007, zitiert nach Kühle, Dr. med Hans-Jürgen, Neurofeedbacktherapie bei ADHS, Giessen 2010 (PDF von Webseite Dr. Kühle, Download Februar 2018), Kapitel 7

  7. Quisenberry, Baker (2015): Dopaminergic mediation of the discriminative stimulus functions of modafinil in rats. Psychopharmacology (Berl). 2015 Dec;232(24):4411-9. doi: 10.1007/s00213-015-4065-0.

  8. Hersey M, Tanda G (2024): Modafinil, an atypical CNS stimulant? Adv Pharmacol. 2024;99:287-326. doi: 10.1016/bs.apha.2023.10.006. PMID: 38467484.

  9. Willie, Renthal, Chemelli, Miller, Scammell, Yanagisawa, Sinton (2005): Modafinil more effectively induces wakefulness in orexin-null mice than in wild-type littermates. Neuroscience. 2005;130(4):983-95.

  10. Ishizuka, Sakamoto, Sakurai, Yamatodani (2003): Modafinil increases histamine release in the anterior hypothalamus of rats. Neurosci Lett. 2003 Mar 20;339(2):143-6. doi: 10.1016/s0304-3940(03)00006-5. PMID: 12614915.

  11. Peterson BS, Trampush J, Maglione M, Bolshakova M, Brown M, Rozelle M, Motala A, Yagyu S, Miles J, Pakdaman S, Gastelum M, Nguyen BT, Tokutomi E, Lee E, Belay JZ, Schaefer C, Coughlin B, Celosse K, Molakalapalli S, Shaw B, Sazmin T, Onyekwuluje AN, Tolentino D, Hempel S (2024): ADHD Diagnosis and Treatment in Children and Adolescents [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2024 Mar. Report No.: 24-EHC003Report No.: 2023-SR-03. PMID: 38657097. METASTUDY