Guanfacine, sold under the brand name Tenex (immediate-release) and Intuniv (extended-release) among others, is an oral alpha-2a agonist medication used to treat attention deficit hyperactivity disorder (ADHD) and high blood pressure.

Common side effects include sleepiness, constipation, and dry mouth. Other side effects may include low blood pressure and urinary problems. It appears to work by activating α_2A-adrenergic receptors in the brain, thereby decreasing sympathetic nervous system activity.

Guanfacine was first described in 1974 and was approved for medical use in the United States in 1986. It is available as a generic medication. In 2023, it was the 263rd most commonly prescribed medication in the United States, with more than 1 million prescriptions. Guanfacine is approved in the US for monotherapy treatment of attention deficit hyperactivity disorder, as well as being used for augmentation of stimulant medications. Guanfacine is also used off-label to treat tic disorders, anxiety disorders, and post-traumatic stress disorder (PTSD).

Guanfacine IR (as brand name Tenex) is FDA approved for the management of hypertension.

Guanfacine XR (as brand name Intuniv) is indicated for the treatment of attention deficit hyperactivity disorder (ADHD), primarily for hyperactive symptoms. It is used both as monotherapy and as adjunctive therapy to stimulant medications. In some cases, it can also help control the side effect profile of stimulant medications. Unlike stimulant medications, guanfacine is regarded as having no abuse potential. However, stimulant medications still remain the first-line treatment for ADHD, and guanfacine is typically only prescribed by itself in patients who cannot take stimulant medications (due to mental or physical side effects).

For attention deficit hyperactivity disorder (ADHD), it is claimed that guanfacine helps individuals better control behavior, inhibit inappropriate distractions and impulses, and inhibit inappropriate aggressive impulses. Systematic reviews and meta-analyses have found guanfacine to be effective in the treatment of ADHD in both children and adults, with a moderate effect size found in adults (Hedges' g = -0.66). A systematic review and meta-analysis also found that guanfacine reduced oppositional behavior in children and adolescents with ADHD who also had or did not also have oppositional defiant disorder, with a small-to-moderate effect size. In any case, guanfacine and other α₂-adrenergic receptor agonists are considered to be less effective than stimulants in the treatment of ADHD, at least when compared on rating scales developed to assess stimulant efficacy.

Guanfacine is also used off-label to treat tic disorders, anxiety disorders such as generalized anxiety disorder, and PTSD. Guanfacine and other α_2A-adrenergic receptor agonists have anxiolytic-like action, thereby reducing the emotional responses of the amygdala, and strengthening prefrontal cortical regulation of emotion, action, and thought. These actions arise from both inhibition of stress-induced catecholamine release, and from prominent, post-synaptic actions in the prefrontal cortex. Due to its prolonged elimination half-life, it also has been seen to improve sleep interrupted by nightmares in PTSD patients. All of these actions likely contribute to the relief of the hyperarousal, re-experiencing of memory, and impulsivity associated with PTSD. Guanfacine appears to be especially helpful in treating children who have been traumatized or abused.

Other indications for guanfacine are drug (opioid, nicotine, cocaine) withdrawals, migraine prophylaxis, and Fragile X Syndrome, among others.