Guanfacine may temper adult ADHD symptoms

Guanfacine extended-release (GXR) may alleviate symptoms of attention-deficit/hyperactivity disorder (ADHD) in adults, a Japanese study has shown.

“[T]he symptom presentation of childhood ADHD often differs from that of adult ADHD, potentially complicating the diagnosis. [Also,] effective treatments for ADHD in adults have limitations,” said the researchers. Moreover, adult ADHD is usually accompanied by medical and/or psychiatric comorbidities. [J Atten Disord 2016;20:1066-1075; J Atten Disord 2018;22:203-228]

As such, adult ADHD is often underdiagnosed and undertreated. [Atten Defic Hyperact Disord 2017;9:47-65] “[Adults with ADHD are more susceptible] to addiction or mood disorders, unsafe behaviour, premature accidental deaths, and suicide, [hence the need for] new treatment options,” they stressed.

The favourable benefit-risk profile of GXR for treating ADHD has been established in paediatric patients. [Eur Neuropsychopharmacol 2014;24:1861-1872; J Am Acad Child Adolesc Psychiatry 2015;54:916-925] “[O]ur study expands current evidence … and demonstrates that GXR was equally efficacious in adult and paediatric patients … [D]ose-optimized GXR improved multiple facets of ADHD in adults,” said the researchers.

Two-hundred participants (64 percent male, mean age 32 years) were randomized 1:1 to receive GXR or placebo. GXR was titrated from 2 to 4–6 mg/day for 5 weeks (optimization), followed by 4–6 mg/day for 5 weeks (maintenance) and then 2 mg/day for 2 weeks (tapering). [J Clin Psychiatry 2020;doi:10.4088/JCP.19m12979]

At week 10, GXR markedly outdid placebo in terms of reductions in ADHD Rating Scale IV total score (least squares mean [LSM], –11.55 vs –7.27; p=0.0005) and subscale scores (LSM, –7.39 vs –4.89; p=0.003 [inattention] and –3.84 vs –2.10; p=0.002 [hyperactivity-impulsivity]). These reductions were sustained from week 4–10.

Favourable safety

Treatment-emergent adverse event (TEAE) rate was higher with GXR vs placebo (81 percent vs 62 percent), as was TEAE-related withdrawal (20 percent vs 3 percent). “[The] discontinuations in the GXR group during the dose-optimization period were mainly due to BP decrease or somnolence and may have been related to the forced dose titration during this period. Guanfacine is a selective α2_A-adrenergic receptor agonist, and its pharmacologic action may cause somnolence and BP reductions,” they explained.

Of note was the significant improvement in the inattention subscale score despite the increased frequency of somnolence, the researchers underlined. “This would suggest that the increased incidence in sedation-related AE did not lead to increased functional impairment.”

Most TEAEs were mild-to-moderate in severity. Apart from one suicide attempt, no other serious TEAEs nor deaths were reported. Despite the lack of major safety issues, the researchers highlighted that it is still imperative to monitor TEAEs at initiation and dose escalations.

Multidimensional improvements

“[Overall, these suggest that] GXR may be a suitable treatment option that offers improvements in core [adult] ADHD symptoms … and some aspects of executive function and quality of life, in addition to having a known safety profile,” they said.

“Given the multidimensional impact of ADHD on an adult’s daily life, the observed benefits on not only ADHD symptoms but also general health status, life productivity, and some executive functioning subscale scores are an important finding,” they added.

The use of multiple rating parameters and flexible dosing regimen are some of the study’s strong points, noted the researchers. “[The flexibility allowed] for individualization of the treatment dose and the potential balancing of side effects with efficacy benefits,” they pointed out.

However, the short treatment duration, Japanese population, and male predominance may preclude generalizability of the findings. As such, the team called for long-term trials to ascertain the potential of GXR across the adult spectrum (taking into consideration age, sex, ethnicity distribution).