Guanfacine (Intuniv)

Mechanism of Action
Guanfacine is not a stimulant. It's a selective alpha-2A adrenergic receptor agonist. It works by stimulating these receptors in the prefrontal cortex, a brain region responsible for attention, impulse control, and working memory. The stimulation leads to reduced sympathetic nerve activity, improving the regulation of attention and emotional responses. Unlike stimulants, guanfacine primarily affects norepinephrine signaling and does not increase dopamine levels.
This makes guanfacine an alternative for treating ADHD, especially for individuals who cannot tolerate stimulants due to side effects, contraindications, or concerns about misuse. Additionally, it can help with sleep issues and emotional dysregulation often associated with ADHD.
Sources:
  1. Wilens TE, et al. "Clinical practice with non-stimulant treatments for ADHD." Journal of the American Academy of Child & Adolescent Psychiatry.
  2. Prescribing Information for Intuniv (Guanfacine Extended-Release), Shire Pharmaceuticals.
  3. Kratochvil CJ, et al. "The role of alpha-2 agonists in ADHD treatment." CNS Drugs.
Clinical Benefits
  1. ADHD (Attention-Deficit/Hyperactivity Disorder):
    • Helps reduce impulsivity, hyperactivity, and distractibility.
    • May be particularly beneficial for individuals with emotional dysregulation or co-occurring sleep issues.
    • Often used as a monotherapy or adjunct to stimulants in children and adolescents.
  2. Sleep Regulation:
    • Its sedative properties can improve sleep onset and quality, especially in individuals with ADHD.
  3. Off-Label Uses:
    • Anxiety disorders
    • Post-Traumatic Stress Disorder (PTSD)
    • Tic disorders

Dosage
Guanfacine is available in two formulations:
  1. Extended-Release (Intuniv):
    • Starting Dose: 1 mg once daily, taken at bedtime or in the morning.
    • Titration: Increase by 1 mg per week based on response and tolerability.
    • Maintenance Dose: Typically 1-4 mg per day.
  2. Immediate-Release:
    • Less commonly used for ADHD but prescribed for conditions like hypertension.
  • Dosage should not exceed 4 mg/day in children aged 6-12 and 7 mg/day in adolescents aged 13-17.

Prevalence of Side Effects
Side effects are dose-dependent and generally mild, with a sedative effect being the most prominent.
  • Common Side Effects (10-30%):
    • Drowsiness or fatigue
    • Dry mouth
    • Dizziness
    • Irritability
  • Less Common Side Effects (1-10%):
    • Low blood pressure (hypotension)
    • Bradycardia (slow heart rate)
    • Abdominal pain
  • Rare but Serious Side Effects (<1%):
    • Syncope (fainting)
    • Rebound hypertension upon abrupt discontinuation

Efficacy and Safety
  • Guanfacine is effective as both monotherapy and adjunct therapy for ADHD, particularly in cases where stimulant medications are insufficient or contraindicated.
  • It is considered safer than stimulants regarding abuse potential but requires monitoring for cardiovascular effects.

Sources
  1. Prescribing Information for Intuniv (Guanfacine Extended-Release), Shire Pharmaceuticals.
  2. Wilens TE, et al. "Clinical practice in treating ADHD with alpha-2 agonists." Journal of the American Academy of Child & Adolescent Psychiatry.
  3. Scahill L, et al. "Extended-release guanfacine in the treatment of ADHD." Clinical Therapeutics.