Higher Guanfacine Doses Found Effective for Adolescent ADHD

While stimulants generally remain first-line medication for ADHD, alternatives are often needed due to side effects or ineffectiveness.   Of the non-stimulant medications, guanfacine and its more recent extended release preparation (trade name Intuniv) is one possible alternative.  Current FDA guidelines specify 4mg per day as the maximum dose, although much of this recommendation is based on younger children.  There is some data suggesting that guanfacine may be less effective in adolescents, and this recent industry sponsored study set out to see if perhaps one reason was due to insufficient dose.  Here the authors conduct a multi-center, double-blind placebo-controlled randomized trial  of extended release guanfacine attempting to achieve a dose of between 0.05 and 0.12 mg/kg/day, which is about the typical dose in younger children on a per weight basis.

The subjects were 314 adolescents between the ages of 13 and 17 with a confirmed ADHD diagnosis.  Psychiatric comorbidity other than oppositional defiant disorder (ODD) was Guanfacineexclusionary.  Most of the sample had previously tried a stimulant.  Subjects at risk for cardiovascular problems or who were taking medications that “have central nervous system effects” were excluded from the study.  Extended release guanfacine was initially dosed at 1mg per day and titrated according to response and tolerability to a maximum of 4mg per day for patients weighing less than 41kg and up to 7mg per day for patients weighing more than 58kg.  The medication was given once per day in the morning.  The primary outcome measure was changes in scores on the ADHD Rating Scale IV, the Clinical Global Impressions scale and the Weiss Functional Impairment Rating Scale.  Side effects and vital signs were also monitored during this 13-week study.

In terms of results, a total of 85% of the sample was able to achieve their optimal dose with nearly half the sample taking 5-7 mg per day.  At the end of the study (using a last on-treatment assessment carry forward analysis), 66.9% of the guanfacine, compared to 45.8% of the placebo group were classified as responders, based on at least a 30% improvment in the ADHD Rating Scale.  Improvement in ADHD symptoms with guanfacine was found to be statistically superior to placebo starting on week 7, although no significant group differences were found on any domains of the functional impairment scale.  In terms of side effects, somnolence was reported in 44% of the guanfacine group with headache occurring in 27%.  As might be expected, small but significant differences were found for heart rate and blood pressure changes compared to placebo. Nine subjects discontinued the medication because of side effects.

The authors concluded that extended release guanfacine at doses up to 7mg per day is more effective than placebo in treating ADHD and was generally well tolerated.

One thing that was a bit unusual for this study  was the high placebo response rate.  Conventional wisdom states that placebo response rates tend to be low in ADHD studies and generally this is true: however, there have been other studies with high placebo response rates particularly with adolescents.

In my own practice, guanfacine is also a medication I consider for youth who can be dysregulated and aggressive, particularly those whose aggression tends to be more reactive.  In some cases I’ve been able to avoid what to me are riskier medications such as antipsychotics.  This study suggests that if patients are tolerating this medication well, it may be worth considering pushing the dose further before giving up on the medication.

I should state that I don’t personally don’t receive any money from the manufacturers of extended release guanfacine.  This study, however, was sponsored by a pharmaceutical company, and I know these days that tends to raise some skepticism about the results.  The lead author is a well respected child psychiatrist who is currently the Director of Child Psychiatry at Massachusetts General Hospital.


Wilens T.  A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder.  JAACAP 2015;54(11):916–925.

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