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Medication: tolerance development

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Medication: tolerance development

In a few cases, tolerance to stimulants may develop.1
This is rather unusual,2, but possible in some cases.34
Tolerance development occurs more frequently at high doses(Kupietz SS, Winsberg BG, Richardson E, Maitinsky S, Mendell N (1988): Effects of methylphenidate dosage in hyperactive reading-disabled children: I. Behavior and cognitive performance effects. J Am Acad Child Adolesc Psychiatry. 1988 Jan;27(1):70-7. doi: 10.1097/00004583-198801000-00011. PMID: 3343209.))5 and to that extent could possibly also be a consequence of overdose. However, there are known cases in which there was certainly no overdose.

1. Types of tolerance development

Types of tolerance development are:3

  • early tolerance development
    • rare
  • gradual or “late tolerance” over a period of years
    • somewhat more frequent than early tolerance
  • “Complete tolerance” (complete loss of benefit from the drug)
    • very rare
  • partial tolerance (partial loss of benefit)
    • more often than full tolerance
    • develop, and possibly a larger percentage who exhibit “partial tolerance” (partial loss of benefit). Strategies to address stimulant tolerance include: changing stimulant class (e.g., from MPH to AMPH and vice versa); taking medication breaks to reset tolerance; using other treatments such as psychotherapy, non-stimulant medications; and clinical reassessment (in light of factors such as medication adherence, comorbid conditions, or the natural history of ADHD over time).
  • Tachyphylaxis
    • rapid form of tolerance development to certain drugs
    • In contrast to classical tolerance, in tachyphylaxis the system is initially exhausted and dose increase is unsuccessful.6

1. Action strategies in case of tolerance development

  • Dose increase of stimulants
    • at best short-term transitional solution
    • what is meant here is not the usual dose adjustment required once or twice within the first year of treatment, but an ongoing loss of efficacy
  • short medication leave can help with tolerance
    • Dose lower on weekends
    • Skip weekends
    • break of several weeks during vacation / vacations
      • can restore long-term effect
  • Change of the active substance
    • from MPH to AMP
    • from AMP to MPH
    • If the substitute is less effective, it may help to switch back after about a month. It has been reported that in quite a few cases the tolerance disappeared after one month.5
      • 3 Interesting individual cases with a treatment pattern of regular changes in drug class are reported by Handelman et al.3
  • Question the reliability of the patient’s medication regimen
  • clinical re-evaluation
    • natural course of ADHD over time?
    • added / removed massive chronic stress?
    • Termination of intensive sports practice?
      • can cause elimination of significant improvement of ADHD symptoms
    • repeat ADHD diagnosis if necessary
    • comorbid diseases
      • added?
      • Treatment changes?
      • Pregnancy?
  • Change other medication
    • especially in case of first-time and sudden development of tolerance
    • Addition of drugs that promote degradation enzyme?
    • Elimination of drugs that are degraded by or inhibit the same degradative enzyme?
  • Changes in stomach or urine pH?

More about this under Drug duration in ADHD.

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