Dextromphetamine is used long-term to treat ADHD. Does the agent's effectiveness in treating the disorder decrease with time? Do the mood elevating properities of the drug attenuate?

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The Therapeutic Goods Administration (TGA) of Australia states that tolerance does develop upon repeated use 'Tolerance and dependence of the amfetamine type develop on repeated administration of dexamfetamine.' (1). This document only mentions tolerance in the general sense.

One article on the use of amphetamine and its derivatives for Treatment Resistant Depression (TRD) note that its effect on psychomotor retardation does not attenuate over time. (2). However, they do note that tolerance does develop to its effects like 'hyperthermia, hypertonia, and anorexia' (2)

In the same article, it is mentioned that other authors have observed declining efficacy over time (2).

These are the most pertinent sources I could find on the question within humans. Animal studies seem to support the notion that tolerance does indeed develop (3).

Considering that the TGA remarks on the tolerance phenomenon, and that there is evidence from other sources to support this notion, I'm inclined to suggest that tolerance does indeed develop with repeated use.


  1. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2017-PI-01667-1
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181580/
  3. https://www.ncbi.nlm.nih.gov/pubmed/1257363

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