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Updated: Jun 4, 2026

Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area
Published on: August 10, 2012
The Dopamine Dilemma-Part II: Could Stimulants Cause Tolerance, Dependence, and Paradoxical Decompensation?
1Dr. Yanofski is a forensic and clinical psychiatrist at the Minor Traumatic Brain Injury (MTBI) Clinic at US Army Garrison, Bamberg, Germany; Dr. Yanofski was working at the San Quentin State Prison, San Quentin, California, during preparation of this manuscript. Dr. Yanofski trained at Johns Hopkins University in Baltimore, Maryland; University of Texas Southwestern in Dallas, Texas; and Yale University in New Haven, Connecticut.
Abstract:
In this commentary, the author calls to attention that stimulants are commonly prescribed to children for years without seeming regard to the lack of studies on efficacy and safety during long-term use. The author examines evidence for stimulants losing efficacy over time and provides multiple possible mechanisms. The potential for paradoxical decompensation, an iatrogenic worsening of symptoms over time, is considered and discussed. Recommendations for detecting and responding to possible stimulant tolerance and dependence are provided.
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