Recommended treatment for attention deficit hyperactivity disorder (ADHD) includes stimulant medication. While these medicines are effective for most ADHD patients, benefits may wear off, suggesting tolerance. This paper reviews the published literature on tolerance to stimulant medication treatment for ADHD. As there are relatively few studies published, pivotal studies and ADHD treatment guidelines were also reviewed. Research demonstrates physiological changes related to continued stimulant usage in neurons and certain brain regions, suggesting a mechanism for tolerance development. One clinical study showed that 24.7% of patients developed tolerance to stimulants in the time of days to weeks; another showed 2.7% developed tolerance over 10 years. Long term follow-up studies demonstrate that medication response may lessen over longer durations of treatment in a high percentage of patients. Strategies to manage tolerance include switching stimulant medicines, drug holidays, or clinical reassessment. Three cases illustrate challenges with treating patients who develop tolerance to stimulant medication. The paucity of research and lack of guidance to clinicians may contribute to significant under recognition of tolerance to stimulant medication. Further research is required to define clinical tolerance for stimulants in ADHD and to provide guidance on identifying and managing tolerance in clinical practice.
Keywords: ADHD; amphetamines; methylphenidate; stimulant medication; tolerance.