Stimulant and Guanfacine combination for ADHD: (#2) Cognitive Effects.

The following study done by Dr. James T. McCracken et al tested the effects of stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD.


  • Age group: 7-14 yr old
  • n= 182
  • Duration: 8-week double-blind randomized controlled trials with three arm comparative trial.

Dose of medications:

  • Guanfacine (GUAN): 1-3 mg/day
  • d-methylphenidate (DMPH): 5-20 mg/day, or
  • combination treatment with DMPH and GUAN (COMB)

Analyses examined treatment effects in 4 cognitive domains:

  • working memory
  • response inhibition
  • reaction time, and
  • reaction time variability.


  • The treatments differed in effects on working memory but not other cognitive domains.
  • Combination treatment improved working memory more than GUAN but was not significantly better than DMPH alone.


  1. Combined treatment with methylphenidate and guanfacine led to greater improvements in working memory than guanfacine alone.
  2. Combined treatment was not significantly superior to methylphenidate alone.
  3. These benefits were not observed on other cognitive domains for any of the treatments.
  4. This study corroborates the lack of efficacy of guanfacine on cognitive outcomes as a monotherapy, and further suggests it does not benefit cognition as an adjunct to stimulant treatment by direct comparison.


  • J Am Acad Child Adolesc Psychiatry. 2016 Aug;55(8):667-73.


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Dr. Harvinder Singh, M.D. (Admin)

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