What is the best approach for a patient with Attention Deficit Hyperactivity Disorder (ADHD), anxiety, and depression, currently on Vyvanse (lisdexamfetamine) 70mg/day and escitalopram 20mg/day, who is still experiencing focus issues, anxiety, and nightmares, considering adding Wellbutrin (bupropion) and prazosin?

Optimizing Treatment for ADHD, Anxiety, Depression, and Nightmares

Adding bupropion 150mg/day to augment the current regimen is reasonable for persistent ADHD symptoms and depression, while prazosin 3mg at bedtime is strongly recommended for nightmare treatment. 1

Addressing the Nightmares First

Prazosin is the evidence-based first-line pharmacologic treatment for nightmares, particularly when associated with trauma or anxiety disorders. 1

• Start prazosin at 1mg at bedtime and titrate by 1-2mg every few days until effective, with an average effective dose around 3mg (though doses from 1-10mg+ have been used successfully). 1
• The 3mg dose you're considering is appropriate and falls within the typical effective range. 1
• Monitor for orthostatic hypotension, especially during titration. 1
• Prazosin works by reducing CNS adrenergic activity, which disrupts REM sleep and contributes to nightmares. 1

Important caveat: Recent evidence suggests prazosin's efficacy may be reduced in patients taking concurrent antidepressants (like escitalopram), though many patients still respond well and it remains first-choice pharmacologic therapy. 1

Adding Bupropion for ADHD and Depression

Bupropion augmentation of SSRIs is a well-established strategy for treatment-resistant depression and can provide additional benefit for ADHD symptoms. 1, 2

• Bupropion 150mg/day is an appropriate starting dose, with the option to increase to 150mg twice daily if needed (maximum 450mg/day). 1
• The combination of escitalopram and bupropion has demonstrated 62% response and 50% remission rates in treatment-resistant depression, significantly higher than SSRI monotherapy alone. 2
• Bupropion has demonstrated efficacy in controlled trials for ADHD, though it is less effective than stimulants for attentional symptoms. 3
• Give the second dose before 3 PM to minimize insomnia risk. 1

Critical Safety Considerations with Bupropion

Do not exceed 450mg/day total dose due to seizure risk and potential for mood destabilization. 1, 4

• Bupropion should be avoided in patients with seizure disorders. 1
• There is evidence suggesting doses above 450mg/day may trigger manic episodes in susceptible individuals, indicating a dose-related threshold for mood destabilization. 4
• Avoid use in highly agitated patients, as bupropion tends to be activating. 1
• Monitor for increased anxiety initially, as this patient already struggles with anxiety symptoms. 1

Optimizing the Current Regimen

The patient is already on Vyvanse 70mg/day (maximum dose) and escitalopram 20mg/day (maximum dose), yet continues to struggle. 1, 5

• Lisdexamfetamine (Vyvanse) at 70mg represents optimal stimulant dosing and has lower abuse potential as a prodrug. 6
• Escitalopram 20mg is the maximum recommended dose and is generally well-tolerated with minimal drug interactions. 5
• The persistent symptoms despite maximum doses of both medications justify augmentation strategies rather than further dose increases. 2

Monitoring the Combined Regimen

Watch for potential interactions and cumulative side effects:

• The combination of a stimulant (Vyvanse), SSRI (escitalopram), and bupropion is commonly used but requires monitoring for increased anxiety, agitation, or sleep disturbances. 1, 2
• Prazosin may cause orthostatic hypotension, particularly important given the stimulant use. 1
• If anxiety worsens with bupropion addition, consider that SSRIs can sometimes aggravate ADHD symptoms and cause frontal apathy. 3

Implementation Strategy

Start prazosin immediately at 1mg at bedtime, titrating every few days to the target 3mg dose based on nightmare response and tolerability. 1

Add bupropion 150mg in the morning after prazosin is stabilized, monitoring for 2-4 weeks before considering dose increase to 150mg twice daily (second dose before 3 PM). 1, 2

Reassess at 4-8 weeks for therapeutic response, as this is the typical timeframe for antidepressant efficacy. 1, 2