From the Guidelines
Guanfacine typically does not increase energy levels, but rather often causes fatigue or drowsiness as a side effect, however, some people with ADHD may paradoxically feel more energetic when taking guanfacine due to improved executive functioning and reduced mental fatigue. Guanfacine is an alpha-2 adrenergic agonist that works by enhancing prefrontal cortex functioning, which can improve attention, impulse control, and working memory 1. When someone with ADHD experiences improved focus and reduced mental effort to complete tasks, they may perceive this as having more energy. Additionally, if guanfacine improves sleep quality by reducing hyperarousal, some individuals might feel more refreshed and energetic during the day.
Key Points
- Guanfacine is typically prescribed at doses ranging from 1-4 mg daily for ADHD, often taken at bedtime to minimize daytime sedation 1.
- The perception of increased energy is not a direct stimulant effect but rather an indirect result of improved cognitive functioning and potentially better sleep quality.
- Guanfacine has been shown to have efficacy in reducing core symptoms of ADHD, although its effect size is less robust than that of stimulant medications, with an effect size of around 0.7 1.
Mechanism of Action
- Guanfacine's mechanism of action is an agonistic effect at alpha-2 adrenergic receptors throughout the brain, leading to enhanced noradrenergic neurotransmission and strengthened regulatory role of the prefrontal cortex 1.
- This can result in improved attention, impulse control, and working memory, which may contribute to the perceived increase in energy levels.
From the Research
Mechanism of Action
- Guanfacine stimulates postsynaptic alfa-2A adrenergic receptors, inhibiting the production of cAMP and closing HCN channels, which enhances the effectiveness of the signal of the pyramidal neurons of the prefrontal cortex (PFC) 2.
- This mechanism improves working memory and attention, and promotes growth and maturation of the dendritic spines of pyramidal neurons of the medial PFC, associated with brain functions such as learning and memory 2.
Effects on Energy Levels
- Guanfacine is not typically associated with increased energy levels, and in fact, one of the most common treatment-emergent adverse events (TEAEs) reported in studies is fatigue (15.2%) 3.
- Another common TEAE is somnolence (38.6%), which suggests that guanfacine may actually decrease energy levels in some individuals 3.
- There is no clear evidence to suggest that guanfacine would increase energy levels, and its mechanism of action does not appear to be related to increasing energy or alertness 2, 4.
Clinical Studies
- Clinical studies have focused on the efficacy and safety of guanfacine in treating attention-deficit hyperactivity disorder (ADHD), and have not reported increased energy levels as a common outcome 3, 5, 4.
- One case study reported a novel consequence of extended release guanfacine ingestion, including cardiogenic pulmonary edema, but did not mention increased energy levels as a symptom 6.