Irritability Comparison: Dexedrine vs. Adderall
There is no direct comparative evidence demonstrating that Dexedrine (dextroamphetamine) causes less irritability than Adderall (mixed amphetamine salts), and both medications share similar side effect profiles including irritability as a potential adverse effect.
Evidence Base for Irritability with Stimulants
The available guidelines and research do not provide head-to-head comparisons specifically examining irritability rates between these two formulations:
Methylphenidate studies in autism spectrum disorder documented irritability as a significant side effect (alongside decreased appetite, insomnia, and emotionality), but these findings apply to methylphenidate, not to comparisons between dextroamphetamine and mixed amphetamine salts 1
The 1999 comparative study between Ritalin and Adderall found both drugs produced "low and comparable levels of clinically significant side effects" without specifically differentiating irritability rates between formulations 2
Historical side effect reviews from the 1980s documented common adverse effects of dextroamphetamine (anorexia, insomnia, stomach pains, weight loss) but did not emphasize irritability as a primary concern 3, 4
Theoretical Considerations
The composition difference may have clinical relevance but lacks empirical support:
- Adderall contains 75% dextroamphetamine and 25% levoamphetamine, while Dexedrine is pure dextroamphetamine 5
- The levoamphetamine component in Adderall theoretically provides more peripheral noradrenergic effects, which could contribute to irritability, but this has not been systematically studied 1
Clinical Management of Stimulant-Related Irritability
When irritability emerges with either medication:
Assess timing of irritability - if it occurs as medication wears off ("rebound irritability"), this suggests the need for extended-release formulations or additional afternoon dosing rather than medication switching 1
Evaluate for comorbid mood disorders - stimulants can produce dysphoria in vulnerable patients, and children may become tearful with tantrums during medication offset 1
Consider dose reduction - irritability may indicate excessive dosing rather than formulation-specific intolerance 6
Monitor systematically - use standardized rating scales at each visit to quantify irritability rather than relying on subjective impressions 6
Common Pitfalls
- Attributing all irritability to medication when behavioral or environmental factors may be primary contributors 1
- Switching formulations without adequate trial duration - allow at least one week at each dose to properly evaluate response 6
- Overlooking the possibility that untreated ADHD symptoms themselves cause irritability, which may improve rather than worsen with appropriate stimulant treatment 1