Guanfacine HCl

Guanfacine, a drug that belongs to a class of medications called α2a specific  adrenergic receptor agonists, more commonly known as alpha agonists, had originally been introduced to the market as an antihypertensive agent. Recently, however, it has also been approved for the treatment of ADHD and represents a represents a novel approach in its pharmacotherapy. Unlike the more traditional stimulant (methylphenidate, amphetamines) and non-stimulant medications (atomoxetine, bupropion) acting mainly on catecholaminergic presynaptic mechanisms, guanfacine acts at postsynaptic level. Its mechanism of action seems to be related to the activation of 2α a-adrenergic receptors in the brain,  tricking the sympathetic nervous system the autonomous system nerve into tuning down its response, which results not only in lower blood pressure, but also a a significant decrease in hyperactivity, impulsivity, insomnia, and emotional dysregulation.

By acting like anxiolytics, guanfacine and other α2A-adrenergic receptor agonists dampen the emotional responses of the amygdala and fortify the prefrontal cortex’s ability to regulate emotion, behavior, and cognition. These effects arise from both the suppression of stress-induced catecholamine release and prominent, post-synaptic actions in the pre-frontal cortex, which are believed to be mediated by the stimulation of post-synaptic α2A-adrenoceptors on dendritic spines.

Studies in monkeys have shown that guanfacine can improve working memory, attention regulation, and behavioral inhibition.

While current scientific evidence suggests that guanfacine is generally more effective than placebo in improving ADHD symptoms among those with ADHD or ASD, the most marked improvement was typically observed in the 6-12 age group. In two systematic reviews focused on children and adolescents, guanfacine was not significantly different than methylphenidate in clinician-rated symptoms, parent-rated symptoms, teacher-rated symptoms, or the ADHD-RS score.

Unlike stimulant medications, guanfacine possesses no abuse potential. Conversely, it might actually help reduce addictive behavior, including compulsive drug use (i.e., nicotine, cocaine). As such, it might be the drug of choice for ADHD patients with the history of drug addiction.

While it is generally not considered the first-line treatment, guanfacine can complement and synergistically enhance the action of stimulants, as it might aid it the facets of ADHD where stimulants do not fully succeed, such as hyperactivity, impulsivity, and self-regulation of behavior and emotions. Moreover, its calming properties make it seem to be tailored to be used to control the side effect profile of stimulant medications. It might also be the drug of choice for patience that do not tolerate stimulant medications well or those for whom they are strongly contraindicated.

The atennuating potential of guanfacine on emotional hyperreactivity has led to multiple studies exploring its applications in the treatment of post-traumatic stress disorder (PTSD). While their results are mostly inconclusive, one study reported favorable outcomes in children with comorbid ADHD. It might also be helpful for adult PTSD patients who do not respond well to selective serotonin reuptake inhibitors (SSRIs).

Guanfacine has also been researched for the treament of withdrawal symptoms from opioids, alcohol, and nicotine. Empyrical data indicates that guanfacine can diminish stress-induced cravings for nicotine in individuals attempting to quit smoking, potentially by enhancing self-control mediated by the prefrontal cortex.

It has been investigated for addressing cognitive, behavioral and emotional difficulties in conditions affecting prefrontal cortex function, such as cognitive and attention difficulties in individuals with traumatic brain injury, stroke, schiztypal disorders, and the elderly.

Lately, guanfacine is being investigated as possible treatment of long COVID.

 

Benefits of taking guanfacine:

• improved executive function;
• better decision making;
• enhanced self-control;
• lessened hyperreactivity;
• improved emotional regulation;
• enhanced working memory;
• better sleep quality;
• reduced hyperactivity;
• improved attention regulation;
• reduced anxiety and restlessness;
• diminished stress-induced compulsive behaviors;
• synergizes with stimulant medication;
• helps with stimulant side effect management;
• possible treatment for long COVID;
• potential alternative treatment for PTSD;
• possible aid in drug use cessation.

Side effects

Severe adverse reactions to guanfacine are rare, occurring in less than 2% of users.
Some of the below side effects are, however, more likely to be experienced upon commencing treatment.

• dry mouth;
• tiredness;
• weakness;
• headache;
• irritability;
• decreased sexual ability;
• decreased appetite;
• abdominal pain;
• nausea;
• vomiting;
• constipation.

It is advised to seek medical advice if the above adverse effects persist and / or are severe. In rare cases, guanfacine might also cause low blood pressure, fainting, blurred vision, rash, and bradycardia – if one is experiencing these symptoms, one should contact their doctor immediately.

 

Interactions and contraindications*

• NSAIDs;
• alcohol;
• CYP3A4 inhibitors, i.e., diltiazem, itraconazole, clarithromycin, erythromycin, ritonavir, ketoconazole, verapamil, goldenseal and grapefruit juice) – reduced dose is recommended;
• CYP3A4 inducers: i.e., glucocorticoids, phenobarbital, phenytoin, rifampicin and St. John’s wort – might require increasing the dose up to double;
• those who suffer from bradyarrhythmia, depression, hypotension, or kidney or liver disease should consult their doctor before prior to introducing guanfacine;
• guanfacine might exacerbate the sedative effects of barbiturates, first generation antihistamines and first generation antipsychotics;
• pregnancy – it is generally contraindicated to take guanfacine during pregnancy.

Dosage

Guanfacine is avalable in immediate and extended release formulation. In case of the former, guanfacine is dosed up to twice daily, with single dose ranging from 1 to 2 mg.

Extended release formulation requires a single 1-4 mg dose per day, taken in the morning or evening at approximately the same time each day. In order to reduce dizziness or daytime sleepiness, it is advised to take guanfacine in the evening.

High-fat meals could potentially speed up th release of the medication, increasing the likelihood of adverse effects.

Typically, it takes about 2-3 weeks to experience the therapeutic effects of guanfacine.