One in three patients had a side effect, but the cardiovascular risks were rare and manageable
STUDY: Iwanami A et al, Advances in Therapy 2026;
STUDY TYPE: Post-marketing surveillance study (prospective observational)
FUNDING: Takeda Pharmaceutical Co., Ltd.
Background
Guanfacine XR is a nonstimulant approved for pediatric ADHD in the US and for adults in Japan. It works by stimulating alpha-2A adrenergic receptors in the prefrontal cortex. This study gathers safety data in adults since its approval in Japan since 2019.
The Study
- 912 adults with ADHD across 155 Japanese clinical sites (no control group)
- Followed for up to 12 months or until they stopped the med
Results
One in three patients (33%) experienced at least one adverse drug reaction:
- Somnolence (15%)
- Dizziness (4%)
- Malaise (4%)
- Postural dizziness (3%)
Most occurred within the first week of starting or after a dose increase.
The cardiovascular side effects peaked upon starting or raising the dose; all resolved with time. They were:
- Low blood pressure or slow heart rate (4.5%)
- Syncope (0.2%)
Among patients who stayed on the drug, ADHD symptoms improved steadily over the year. After a year, 59% of patients rated themselves “much” or “very much” improved on the Patient Global Impression scale. Symptom scores on the ADHD-RS-IV dropped about 45% from baseline. Patients with co-occurring autism spectrum disorder improved at similar rates.
Only 45% of patients were still taking the drug at 12 months. Side effects drove 36% of discontinuations. Women and patients on concomitant psychotropics or cardiovascular medications had higher rates of side effects.
Limitations
No control group, open-label design, no systematic laboratory monitoring, and survivor bias (effectiveness data reflect only those who stayed on the drug).
Practice Implications
- Benefits build steadily with guanfacine in adults.
- Serious low blood pressure and fainting events were rare, and all resolved.
- Start at 1–2 mg and titrate slowly in weekly 1 mg increments to reduce side effects.
— Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
