Is it safe to increase Seroquel (quetiapine) to 100mg at bedtime and add Wellbutrin (bupropion) 150mg, titrating to 300mg, for an adult female patient with persistent mood symptoms and Attention Deficit Hyperactivity Disorder (ADHD) symptoms?

Medication Adjustment for Mood and ADHD Symptoms

Direct Recommendation

Yes, you can safely increase Seroquel to 100mg at bedtime and add Wellbutrin 150mg with titration to 300mg for this patient, but you must follow a specific titration schedule and monitor for key adverse effects. 1, 2

Quetiapine (Seroquel) Dose Increase

The proposed increase from 50mg to 100mg at bedtime is appropriate and well within FDA-approved dosing parameters. 1

• For bipolar depression specifically, the FDA label indicates quetiapine should be administered once daily at bedtime, starting at 50mg on Day 1, increasing to 100mg on Day 2, then 200mg on Day 3, and 300mg on Day 4, with a target dose of 300mg/day 1
• Your proposed increase to 100mg represents a conservative, gradual titration that is safer than the FDA's standard schedule 1
• Quetiapine at 300-600mg daily has demonstrated efficacy for bipolar depression in multiple randomized controlled trials, with significant improvements in Montgomery-Asberg Depression Rating Scale scores compared to placebo 3
• The current 50mg dose is subtherapeutic for mood disorders; therapeutic dosing for bipolar depression ranges from 300mg daily 1, 3

Bupropion (Wellbutrin) Addition and Titration

Start bupropion at 150mg once daily in the morning, then increase to 300mg once daily after 4 days if tolerated. 2

Specific Dosing Protocol

• Day 1-4: Bupropion XL 150mg once daily in the morning 2
• Day 5 onward: Increase to 300mg once daily in the morning if the patient tolerates the initial dose 2
• The medication must be taken in the morning to minimize insomnia risk, given its activating properties 4
• Swallow tablets whole; do not crush, divide, or chew 2

Evidence for ADHD Treatment

Bupropion 300mg daily demonstrates moderate efficacy for adult ADHD symptoms. 5, 6

• A randomized, double-blind study of 42 adults with ADHD showed bupropion 150mg daily was significantly more effective than placebo in reducing ADHD symptoms on the Conners' Adult ADHD Rating Scale after 6 weeks 5
• A Cochrane systematic review of 438 participants found low-quality evidence that bupropion decreased ADHD symptom severity (standardized mean difference -0.50,95% CI -0.86 to -0.15) and increased the proportion achieving clinical improvement (RR 1.50,95% CI 1.13 to 1.99) 6
• The standard therapeutic dose for ADHD is 300mg daily of the extended-release formulation 4, 6

Critical Safety Considerations

Seizure Risk Management

The most important safety concern with this combination is seizure risk, which requires careful attention to dosing limits. 2

• The maximum dose of bupropion XL is 450mg daily, but you should not exceed 300mg daily in this patient to minimize seizure risk 2
• Gradual dose titration is mandatory to reduce seizure risk 2
• Avoid bupropion if the patient has any history of seizures, eating disorders (bulimia/anorexia), or abrupt discontinuation of alcohol or benzodiazepines 4, 2

Drug Interaction Monitoring

Quetiapine and bupropion do not have significant pharmacokinetic interactions, making this combination generally safe. 1, 2

• Quetiapine is metabolized primarily by CYP3A4, while bupropion is metabolized by CYP2B6 and inhibits CYP2D6 1, 2
• No dose adjustment of quetiapine is needed when adding bupropion 1, 2
• Monitor for additive CNS effects, particularly sedation from quetiapine and activation from bupropion 1, 2

Monitoring Parameters

Monitor the following at baseline and during titration: 4, 2

• Blood pressure (bupropion can increase BP; avoid in uncontrolled hypertension) 4
• Weight and metabolic parameters (quetiapine can cause weight gain and metabolic changes) 3
• Mood symptoms and suicidal ideation, especially in the first few weeks 2
• Sleep quality (quetiapine causes sedation; bupropion can cause insomnia) 4, 1
• ADHD symptoms using standardized rating scales after 6-8 weeks 4, 5

Common Pitfalls to Avoid

Do not dose bupropion twice daily with the XL formulation. 2

• Bupropion XL is designed for once-daily morning administration only 2
• If using the SR formulation instead, dose 150mg twice daily with the second dose before 3 PM 4

Do not increase quetiapine too rapidly beyond 100mg. 1

• While rapid titration to higher doses (300mg) is possible and has been studied, the patient is already on 50mg, so a stepwise increase to 100mg, then reassessing before further increases is prudent 1, 7

Do not forget to counsel about sedation timing. 1, 3

• Quetiapine causes significant sedation and should be taken at bedtime 1
• The most common adverse effects are dry mouth, sedation, somnolence, and dizziness 3

Reassessment Timeline

Evaluate treatment response at 6-8 weeks after reaching target doses. 4, 6

• ADHD symptoms may improve within the first few weeks, but full assessment requires 6-8 weeks at therapeutic doses 4, 6
• Mood symptoms typically require several weeks to months of treatment for full response 2
• If no response after 6-8 weeks at 300mg bupropion and 100-300mg quetiapine, consider alternative treatments 4, 6