How would you transition a patient with a family history of bipolar disorder and ongoing reactive outbursts, currently on Tenex (guanfacine) 1mg three times a day, to Intuniv (guanfacine extended-release)?

Transitioning from Tenex to Intuniv

Convert the total daily dose of Tenex (immediate-release guanfacine) 1mg three times daily (3mg/day total) to Intuniv (guanfacine extended-release) 3mg once daily in the evening, making the switch directly without tapering or overlap. 1

Critical Safety Consideration: Family History of Bipolar Disorder

This patient requires extremely careful monitoring during the transition due to her family history of bipolar disorder, as guanfacine can precipitate secondary mania or hypomania in vulnerable children with bipolar risk factors. 2 In a case series, all five children who developed behavioral activation (resembling acute hypomanic or manic episodes) on guanfacine had clear clinical or familial risk factors for bipolar disorder. 2

• Monitor closely for signs of behavioral activation including increased irritability, decreased need for sleep, pressured speech, racing thoughts, or escalation of reactive outbursts during and after the transition. 2
• If manic or hypomanic symptoms emerge, discontinue guanfacine immediately and reassess the diagnosis. 2

Direct Conversion Protocol

The conversion is straightforward: switch from Tenex 1mg TID (3mg total daily) to Intuniv 3mg once daily, administered in the evening. 1, 3

• Intuniv extended-release is NOT substitutable on a mg-for-mg basis with immediate-release guanfacine due to different pharmacokinetics, but in this case the total daily doses align appropriately. 3
• Evening administration is strongly preferred to minimize daytime somnolence and fatigue, which are the most common adverse effects. 1
• Make the switch abruptly without tapering the Tenex or overlapping medications—simply stop the Tenex and start Intuniv the next day. 4 A study in healthy adults demonstrated that abrupt cessation of guanfacine extended-release (even at 4mg/day) did not cause clinically significant rebound hypertension compared to tapering. 4

Cardiovascular Monitoring Requirements

Obtain baseline blood pressure and heart rate before making the switch, then monitor these parameters weekly during the first month after transition. 1

• Expect modest decreases in blood pressure (1-4 mmHg) and heart rate (1-2 bpm), which are typically not clinically significant. 1
• However, 5-15% of patients may experience more substantial decreases requiring closer monitoring or dose adjustment. 1
• If bradycardia (heart rate <60 bpm) or symptomatic hypotension develops, reduce the dose or discontinue. 1

Timeline for Therapeutic Response

Counsel the family that Intuniv requires 2-4 weeks before clinical benefits become apparent, unlike stimulants which work immediately. 1

• The reactive outbursts may not improve immediately after the switch—patience and consistent dosing for several weeks are essential before determining treatment response. 1
• Do not prematurely increase the dose or add additional medications during the first 2-4 weeks unless safety concerns arise. 1

Monitoring for Treatment Response

Systematically assess ADHD symptoms and reactive outbursts at 2 weeks and 4 weeks post-transition using parent and teacher reports. 1

• If reactive outbursts persist after 4 weeks on Intuniv 3mg daily, consider that guanfacine may have limited efficacy for oppositional symptoms in this patient. 1
• Guanfacine has effect sizes around 0.7 compared to placebo for ADHD symptoms, which is smaller than stimulants (effect size ~1.0). 1

Alternative Considerations if Intuniv Fails

If reactive outbursts continue after 4 weeks on optimized Intuniv dosing:

• Consider adding a stimulant medication to Intuniv, as extended-release guanfacine is FDA-approved specifically for adjunctive therapy with stimulants. 1
• Alternatively, consider switching to atomoxetine, which has warnings for emergent aggressive behavior or hostility but may be effective for ADHD with comorbid oppositional symptoms. 5
• Avoid adding clonidine to guanfacine, as both work through the same alpha-2A adrenergic receptor mechanism and would increase sedation and cardiovascular effects without clear evidence of superior efficacy. 1

Critical Discontinuation Warning

If Intuniv ultimately needs to be discontinued, taper by 1mg every 3-7 days to avoid rebound hypertension—never stop abruptly. 1 While one study showed abrupt cessation was safe in healthy adults, 4 clinical guidelines recommend tapering in pediatric patients to minimize risk. 1

Common Pitfalls to Avoid

• Do not split, crush, or chew Intuniv tablets—they must be swallowed whole to maintain extended-release properties. 1 If the patient cannot swallow tablets, discuss with pharmacy about appropriate liquid formulations or switching back to immediate-release with adjusted dosing schedules. 1
• Do not expect immediate improvement in reactive outbursts—the delayed onset of 2-4 weeks is a critical counseling point for families. 1
• Do not overlook the bipolar risk—this patient's family history makes her particularly vulnerable to guanfacine-induced behavioral activation. 2