Stimulant and Guanfacine combination for ADHD: (#1) Cardiovascular Effects.


Q: Is this combination safe and well tolerated from cardiovascular side effect profile of individual medications?


Stimulants are known for increase in pulse and blood pressure in selective patients, and guanfacine having opposite effects. The following study done by Sayer et al examined cardiovascular (CV) effects of guanfacine immediate-release (GUAN-IR), dexmethylphenidate extended-release (DMPH), and their combination (COMB) during acute and long-term treatment of youth with ADHD.



  • Age group: 7-14 yr old
  • n= 207
  • Duration: 8-week double-blind randomized trial


Dose of medications:

  • GUAN-IR: 1-3 mg/day
  • DMPH: 5-20 mg/day, or
  • COMB with fixed-flexible dosing and titrated to optimal behavioral response.



  • Heart rate
  • systolic blood pressure (BP),
  • diastolic BP, and
  • electrocardiograms were assessed at baseline, end of blinded optimization, and over a 1-year open-label maintenance phase.




(1) During acute titration:

  • GUAN-IR: decreased heart rate, systolic BP, and diastolic BP.
  • DMPH increased heart rate, systolic BP, diastolic BP, and QTc interval.
  • COMB increased diastolic BP, but had no effects on heart rate, systolic BP, or QTc.


(2) During maintenance phase:

  • GUAN-IR associated decreases in heart rate and DMPH-associated increases in systolic BP returned to baseline values.
  • Other variables across the three groups remained unchanged from the end of blinded titration.
  • There were no discontinuations due to CV adverse events.



  1. GUAN-IR, DMPH, and COMB were well tolerated and safe.

  2. Expected changes in CV parameters during acute titration were seen in GUAN-IR and DMPH groups, with COMB values falling intermediately between the two other treatment groups.

  3. No serious CV events occurred in any participant.

  4. GUAN-IR- and DMPH-associated CV changes generally returned to baseline with sustained therapy.

  5. These data suggest that COMB treatment might attenuate long-term CV effects of GUAN-IR and stimulant monotherapy, possibly reducing risk of the small but statistically significant changes associated with either single treatment.



  • J Child Adolesc Psychopharmacol. 2016 Dec;26(10):882-888.

Post by Dr. Harvinder Singh, M.D.

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