Will Patients With ADHD Benefit From Stimulant-Guanfacine Combo?
Abstract
A comprehensive clinical study finds that combining guanfacine and methylphenidate decreased some ADHD symptoms, but a lack of cognitive improvements may suggest monotherapies will remain the preferred option.
While stimulants are still the primary pharmaceutical option for treating attention-deficit/hyperactivity disorder (ADHD), guanfacine—an α2A receptor agonist approved for ADHD in 2010—has emerged as an alternative option for patients who do not respond to first-line stimulant therapy. Could combining stimulants with the antihypertensive lead to greater improvements in patients with ADHD than either medication alone?
Robert Bilder, Ph.D., thinks the sedative properties of guanfacine might explain why combining it with methylphenidate in children with ADHD did not lead to cognitive improvements.
To explore this question, researchers at the University of California, Los Angeles (UCLA) enrolled youth aged 7 to 14 with ADHD in an eight-week, double-blind trial in which participants received immediate-release guanfacine (1 mg to 3 mg daily), extended-release d-methylphenidate (5 mg to 20 mg daily), or a combination of the two medications. The children’s symptoms were assessed using the ADHD Rating Scale-Version IV (ADHD-RS-IV), and overall response rate was gauged using the Clinical Global Impression-Improvement (CGI-I) ratings.
While the effects were modest, there was a statistical improvement in symptoms among the patients taking the combination therapy compared with those taking monotherapies, the authors reported in the August issue of Journal of the American Academy of Child and Adolescent Psychiatry. ADHD-RS-IV total score, for example, dropped by 18.3 points in the group that received the combination of the medications compared with 15.8 points for methylphenidate and 16.7 for guanfacine.
In addition, 75 percent of the patients taking both drugs achieved a treatment response by the study’s end (measured as at least a 30 percent improvement in ADHD-RS-IV scores plus a rating of “much improved” or better on the CGI-I) compared with 62 percent for methylphenidate and 63 percent for guanfacine.
In contrast, the combination of guanfacine and methylphenidate had limited effects on cognitive performance, the authors noted in a separate report. The combination therapy was associated with improvements in working memory that were better than guanfacine alone but roughly the same as methylphenidate alone; cognitive performance was similar among the groups in all other measures evaluated.
While the safety and tolerability profiles of the combination therapy were about the same as the individual medications, Timothy Wilens, M.D., chief of child and adolescent psychiatry at Massachusetts General Hospital, told Psychiatric News that the limited cognitive effects of the combination therapy make it unlikely that clinicians will favor the combination therapy over monotherapy.
Because both medications are known to improve attention and hyperactivity symptoms, researchers are now looking for ways to improve “meta” ADHD challenges, such as the ability to prioritize, organize, or plan effectively, Wilens, who was not a part of this trial, explained.
“And given that the symptom differences weren’t even that huge among the groups, I think most people will still default to monotherapy when prescribing ADHD medication to children when they factor in the potential benefits versus issues like medication adherence and copays,” he said.
Study coauthor Robert Bilder, Ph.D., the Michael E. Tennenbaum Family Professor of Psychiatry and Biobehavioral Sciences at UCLA, agreed that the methylphenidate-guanfacine combination is likely not the magic bullet that some clinicians had hoped for.
Bilder noted that one reason the patients taking methylphenidate and guanfacine experienced greater improvements in ADHD symptoms than cognition may be due to the sedative effects of guanfacine, which may interfere with the cognitive benefits of the medication. Another possibility, he said, is that the tests used to evaluate cognition in the study failed to fully capture cognitive improvements.
“But while we focused on the average group effects, there could be individual cases where using these medications in conjunction makes sense,” he said. “Doctors should just have [tempered] expectations and not anticipate any dramatic effects.”
This study was supported by a Research Center Grant from the National Institute of Mental Health. ■
