Subject:
(Scahill S et al, Am J Psychiatry 2016;172:1197–1206)

Short Description:

Children with autism spectrum disorder (ASD) often have symptoms of ADHD. While it’s not always easy to distinguish them from the core features of autism, symptoms such as impulsivity, hyperactivity, and distractibility do occur, and we often use medications to target them. Stimulants are fairly effective but tend to cause more side effects in autistic ADHD kids than in children with pure ADHD. Atomoxetine was only equivocally effective in one trial, and the immediate-release version of guanfacine was tested in a small open-label trial, resulting in improvement in about half the subjects.

Recognizing the need for more data, researchers conducted the first ever randomized placebo-controlled trial of guanfacine in ASD/ADHD, in this case using the extended-release (ER) version. Children between the ages of 5 and 14 with a diagnosis of ASD with accompanying impulsivity, hyperactivity, and distractibility were randomly assigned to either ER guanfacine (n = 30) or placebo (n = 32). During this 8-week trial, ER guanfacine was started at 1 mg once a day for all children. Depending on the child’s weight and response, a maximum of 4 mg daily could be prescribed. The primary outcome measure was change from baseline on the parent version of the Aberrant Behavior Checklist (ABC) hyperactivity subscale, which was assessed at weeks 4, 6, and 8. The Clinical Global Impression-Improvement (CGI-I) scale was also used.

ER guanfacine was effective. At the end of 8 weeks, the medication group showed a 44% reduction in scores on the ABC hyperactivity subscale compared to 13% for the placebo group. For the ER guanfacine group, half were rated “much improved” or “very much improved” on the CGI-I, whereas fewer than 10% of the placebo group were so rated. Significant improvements were seen in both hyperactivity and inattention vs. placebo. The most frequently prescribed dose in both groups was 3 mg. Overall, ER guanfacine was well tolerated. The most common complaints were drowsiness, fatigue, and loss of appetite. Drops in blood pressure and heart rate from baseline were seen in the guanfacine group. Blood pressure normalized by the end of 8 weeks, but heart rate did not, remaining about 10 points below baseline. This effect was not considered clinically significant.

CCPR’s Take: This was a small study of short duration, but the results were promising. When using ER guanfacine, start with 1 mg in the morning and titrate up slowly as needed. Dose it in the evening if the child becomes drowsy. By the way, ER guanfacine is now available as a cheap generic, so don’t feel guilty prescribing it. On the other hand, the ER version’s duration of action is only marginally longer than the IR version (about 24 hours vs. about 17 hours) so you don’t gain much by choosing it.