Stimulant and Guanfacine combination for ADHD: (#3) Comorbid Oppositional Symptoms in ADHD.

The following study by Robert L. Findling et al tested the effect of guanfacine extended release (GXR) adjunctive to a psychostimulant on oppositional symptoms in children and adolescents with ADHD.


  • Age group: 6-17 yr old
  • n= 207
  • Duration: 9-week double-blind, placebo-controlled dose-optimization study = dose optimization (5 weeks), dose maintenance (3 weeks), and dose tapering (1 week).
  • Inclusion criteria: Subjects were required to have exhibited partial but suboptimal response to treatment with a long-acting oral psychostimulant for ≥4 weeks prior to screening.

Dose of medications:

  • During dose optimization: GXR was initiated at 1 mg/day and titrated in 1-mg/week increments (up to 4 mg/day) to the optimal dose.
  • Subjects continued taking their stable morning psychostimulant dose in addition to morning (a.m.) or evening (p.m.) doses of GXR or placebo. 


  • Significant reductions from baseline to the final on-treatment assessment on the oppositional subscale of the CPRS–R:L were seen with GXR plus psychostimulant compared with placebo plus psychostimulant.
  • Treatment-emergent adverse events (TEAEs) were reported by 77.3%, 76.3%, and 63.4% of subjects in the GXR a.m., GXR p.m., and placebo groups, respectively.
  • The two most commonly reported TEAEs were headache (21.3% [32/150]) and somnolence (14.0% [21/150]) in the GXR a.m. plus psychostimulant group.
  • The two most commonly reported TEAEs were headache (21.1% [32/152]) and somnolence (13.2% [20/152]) in the GXR psychostimulant group.


  1. GXR adjunctive to a psychostimulant significantly reduced oppositional symptoms compared with placebo plus a psychostimulant in subjects with ADHD and a suboptimal response to psychostimulant alone.
  2. For subjects with significant oppositional symptoms, the mean (SD) optimal dose of GXR was 3.3 (0.95) mg/day for GXR plus psychostimulant overall.
  3. Significant efficacy as measured by the oppositional subscale of the CPRS–R:L was also demonstrated in the subgroup of subjects presenting with significant oppositional symptoms at baseline. 
  4. Most TEAEs were mild or moderate in severity; and most occurred during the dose-optimization period.


  • J Child Adolesc Psychopharmacol. 2014 Jun 1; 24(5): 245–252.

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Dr. Harvinder Singh, M.D. (Admin)

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