Is an alpha agonist like guanfacine a reasonable option for a patient with Attention Deficit Hyperactivity Disorder (ADHD) and Post-Traumatic Stress Disorder (PTSD) who failed a trial of Strattera (atomoxetine) and cannot take stimulants due to a history of seizures, while already on 5mg of Prazosin (prazosin) for PTSD?

From the Guidelines

Guanfacine is a reasonable option for a patient with comorbid ADHD and PTSD who failed Strattera and cannot take stimulants due to seizure risk, even while on 5 mg of prazosin for PTSD. I would recommend starting with guanfacine extended-release (Intuniv) at 1 mg daily, taken in the morning, and titrating up by 1 mg weekly as needed and tolerated to a target dose of 3-4 mg daily, as supported by the pharmacological properties of guanfacine 1. Monitor blood pressure and heart rate regularly, especially during dose adjustments, as guanfacine can cause hypotension and bradycardia. While prazosin (an alpha-1 antagonist) and guanfacine (an alpha-2 agonist) work on different adrenergic receptor subtypes, their combined use may potentially enhance hypotensive effects, so careful monitoring is essential. Some key points to consider when prescribing guanfacine include:

• Guanfacine's mechanism of action, which involves stimulating alpha-2A adrenergic receptors in the prefrontal cortex, enhancing working memory and attention while reducing impulsivity 1.
• The differences in potency and specificity between guanfacine and clonidine, with guanfacine being approximately ten times less potent than clonidine and having a higher specificity to alpha-2A receptors 1.
• The potential benefits of alpha-2 agonists in reducing hyperarousal symptoms of PTSD, which may offer dual benefits for this patient's comorbid conditions. Overall, guanfacine's unique mechanism of action and potential benefits for both ADHD and PTSD symptoms make it a viable alternative for this patient.

From the FDA Drug Label

In several well-controlled studies, guanfacine was administered together with diuretics with no drug interactions reported In the long-term safety studies, guanfacine hydrochloride was given concomitantly with many drugs without evidence of any interactions The principal drugs given (number of patients in parentheses) were: ... sedatives and hypnotics (103), ... antihyperlipidemics (29), ... beta blockers (10) There have been spontaneous postmarketing reports of mania and aggressive behavioral changes in pediatric patients with attention-deficit hyperactivity disorder (ADHD) receiving guanfacine hydrochloride

• Guanfacine is used to treat ADHD and hypertension.
• The drug label does not explicitly address the use of guanfacine in patients with PTSD who are taking prazosin.
• However, it does mention that guanfacine has been given concomitantly with many drugs, including sedatives and hypnotics, without evidence of interactions.
• Given the patient's history of seizures and failure of Strattera (atomoxetine), guanfacine may be considered as an option for treating ADHD.
• However, caution should be exercised due to the potential for mania and aggressive behavioral changes in patients with ADHD receiving guanfacine.
• The patient is already taking 5mg of Prazosin (prazosin) for PTSD, and the label does not provide direct information on interactions between guanfacine and prazosin.
• Therefore, a conservative clinical decision would be to proceed with caution and monitor the patient closely for any potential interactions or adverse effects 2.

From the Research

Treatment Options for ADHD and PTSD

• Guanfacine is an alpha agonist that can be used to treat ADHD, and it has a different mechanism of action compared to stimulants and atomoxetine 3.
• Guanfacine stimulates postsynaptic alpha-2A adrenergic receptors, which can improve working memory and attention, and it may also promote growth and maturation of dendritic spines in the prefrontal cortex 3.
• In patients with ADHD and comorbid tic disorders, guanfacine has been shown to reduce ADHD symptoms and improve tic symptoms 4.
• However, the quality of evidence for guanfacine in treating ADHD in children with tics is very low 4.

Considerations for Patients with PTSD

• Psychostimulants, such as those used to treat ADHD, may have a potential off-label use in treating PTSD, as they can increase dopamine release and improve symptoms 5.
• However, this is based on a single case report, and more research is needed to confirm the effectiveness of psychostimulants in treating PTSD 5.
• Guanfacine, as an alpha agonist, may be a reasonable option for patients with ADHD and PTSD who cannot take stimulants due to a history of seizures or other contraindications.
• The patient is already on 5mg of Prazosin (prazosin) for PTSD, and guanfacine can be used concomitantly with prazosin, but the potential interactions and effects should be closely monitored 3, 4.

Previous Treatment with Atomoxetine

• The patient has failed a trial of Strattera (atomoxetine), which is a selective norepinephrine reuptake inhibitor used to treat ADHD 6, 7.
• Atomoxetine has been shown to be effective in treating ADHD in children and adults, but it may not be as effective as stimulants or other treatments in some cases 6, 7.
• The patient's failure to respond to atomoxetine does not necessarily preclude the use of guanfacine, as these medications have different mechanisms of action and may be effective in different patients 3.