Can Wellbutrin (bupropion) help a patient on Depakote (valproate) with Attention Deficit Hyperactivity Disorder (ADHD) and excessive sleepiness?

Bupropion for ADHD and Excessive Sleepiness in Patients on Depakote

Yes, bupropion (Wellbutrin) can help treat ADHD symptoms in patients taking Depakote (valproate), and it may also counteract sedation caused by valproate, though it is a second-line agent compared to stimulants. 1

Evidence for Bupropion in Adult ADHD

Bupropion has demonstrated efficacy for adult ADHD as an alternative to stimulants. The evidence shows:

• Low-quality evidence indicates bupropion decreases ADHD symptom severity (standardized mean difference -0.50) and increases the proportion of patients achieving clinical improvement (risk ratio 1.50) compared to placebo 2

• Extended-release bupropion at doses of 150-450 mg daily has been studied in multiple trials, with typical maintenance doses of 100-150 mg twice daily (SR formulation) or 150-300 mg daily (XL formulation) 3, 2

• Bupropion works as a norepinephrine-dopamine reuptake inhibitor (NDRI), modulating the reward-pleasure mesolimbic dopaminergic system while also affecting noradrenergic neurotransmission 4

• A randomized controlled trial in 42 adults with ADHD showed significant improvement in CAARS scores after 6 weeks of bupropion 150 mg/day compared to placebo 5

Addressing Valproate-Induced Sedation

Bupropion may specifically help with excessive sleepiness caused by Depakote:

• Stimulants and bupropion have been used to treat apathy and sedation due to medications or medical conditions, though typically at lower doses than used for ADHD 1

• Valproate commonly causes sedation as a side effect, and bupropion's activating properties can counteract this 3

Safety Considerations When Combining with Valproate

The combination of bupropion and valproate requires monitoring but is not contraindicated:

• No published studies specifically examine bupropion combined with stimulants or other psychotropic medications for ADHD, and the Physicians' Desk Reference does not warn against such combinations 3

• Monitor for seizure risk, as bupropion lowers seizure threshold in high doses, though this is primarily a concern in patients with eating disorders, seizure history, or abrupt benzodiazepine/alcohol withdrawal 3

• Monitor cardiovascular parameters including blood pressure and heart rate regularly, particularly during initial therapy and dose adjustments 3

• Watch for psychiatric side effects including anxiety, insomnia, and agitation, which may be exacerbated when combining medications 3

Clinical Algorithm for This Patient

Start with the following approach:

1. Begin bupropion SR 100-150 mg daily or XL 150 mg daily in the morning, as this timing minimizes insomnia risk 3

2. Titrate gradually over 3-4 weeks to maintenance doses of 150-300 mg daily (XL) or 100-150 mg twice daily (SR), monitoring for side effects 3, 2

3. Schedule monthly follow-up visits initially to assess ADHD symptom response, sedation improvement, and monitor for adverse effects 3

4. Assess response at 6 weeks, as this is the timeframe used in efficacy studies 2, 5

5. If inadequate response to bupropion alone, consider adding a stimulant medication (methylphenidate or amphetamine), as bupropion and stimulants can be combined with appropriate monitoring 1, 3

Important Caveats

Bupropion is a second-line agent for ADHD:

• Stimulants remain first-line treatment with more robust evidence for efficacy in ADHD 1

• Bupropion's effect sizes are smaller than methylphenidate based on teacher and parent ratings, though head-to-head trials show comparable efficacy 6

• The evidence quality is low, meaning further research may change these effect estimates 2

Specific monitoring requirements:

• Check blood pressure and heart rate at each visit during combination therapy 3

• Screen for contraindications including seizure history, eating disorders, and abrupt alcohol/benzodiazepine withdrawal 3

• Monitor for worsening anxiety, insomnia, or mood changes, which are common side effects of both bupropion and can be problematic in ADHD patients 3, 2

Tolerability profile:

• Bupropion's tolerability is similar to placebo in clinical trials, with withdrawal rates due to adverse effects comparable between groups (risk ratio 1.20) 2

• Common side effects include decreased appetite, insomnia, anxiety, headache, and dry mouth, but these are generally manageable 3, 2