Medications: Adaptation reactions

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
• 1. Action strategies in case of tolerance development

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 tolernaz
• “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.⁷
    • 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.