Can Qelbree (Viloxazine) 200mg be combined with Auvelity (dextromethorphan/bupropion), Wellbutrin (Bupropion) 300mg, and Zoloft (Sertraline) 25mg?

Combining Qelbree with Auvelity, Wellbutrin, and Zoloft: Safety Concerns

The combination of Qelbree (viloxazine) 200mg with Auvelity (dextromethorphan/bupropion), Wellbutrin (bupropion) 300mg, and Zoloft (sertraline) 25mg is not recommended due to significant risk of serotonin syndrome, drug-drug interactions, and overlapping side effects that could increase morbidity and mortality.

Major Safety Concerns

1. Duplicate Medications and Drug Interactions

• Auvelity already contains bupropion, making the additional Wellbutrin redundant and potentially dangerous
• Qelbree (viloxazine) is a moderate sensitive CYP1A2 substrate and is not recommended for coadministration with other medications that affect this pathway 1
• Bupropion is a CYP2D6 inhibitor that can increase blood levels of SSRIs like sertraline (Zoloft), increasing toxicity risk 2

2. Serotonin Syndrome Risk

• The combination of multiple serotonergic agents (Qelbree, Zoloft, and potentially Auvelity via dextromethorphan) significantly increases the risk of serotonin syndrome 3
• Serotonin syndrome can develop within 24-48 hours of combining serotonergic medications with symptoms including:
  • Mental status changes (confusion, agitation, anxiety)
  • Neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity)
  • Autonomic hyperactivity (hypertension, tachycardia, diaphoresis)
  • In severe cases: fever, seizures, arrhythmias, unconsciousness, and death 3

3. Seizure Risk

• Both bupropion products (Wellbutrin and Auvelity) carry seizure risks that are dose-dependent 4
• Combining two bupropion-containing products significantly increases this risk
• The American Academy of Family Physicians cautions that bupropion should not be used in patients with seizure disorders 5

Specific Medication Interactions

Qelbree (viloxazine) with other medications:

• As a norepinephrine reuptake inhibitor, Qelbree can interact with other medications affecting norepinephrine and serotonin systems
• FDA labeling specifically warns against combining with moderate sensitive CYP1A2 substrates 1

Auvelity (dextromethorphan/bupropion) interactions:

• Contains dextromethorphan which has serotonergic properties
• The FDA label specifically warns against combining with other serotonergic drugs including SSRIs like Zoloft 4
• Contains bupropion, making additional Wellbutrin redundant and dangerous

Wellbutrin (bupropion) interactions:

• Increases risk of seizures, especially at higher doses
• Inhibits CYP2D6, potentially increasing sertraline levels 5
• Combining with Auvelity would result in excessive bupropion exposure

Zoloft (sertraline) interactions:

• As an SSRI, increases serotonin levels and risk of serotonin syndrome when combined with other serotonergic agents 3
• Metabolism affected by bupropion, potentially leading to increased sertraline levels and toxicity 2

Recommended Approach

1. Do not combine these four medications
2. Choose one antidepressant approach:
   • If targeting depression: Consider either Auvelity OR a combination of Wellbutrin with Zoloft (at appropriate doses) 6
   • If targeting ADHD: Consider Qelbree alone or with a single antidepressant after careful evaluation
3. When combining any two psychotropic medications:
   • Start with low doses
   • Increase doses slowly
   • Monitor closely for adverse effects, especially in the first 24-48 hours after dose changes 3
   • Watch for signs of serotonin syndrome, seizures, or other adverse effects

Common Pitfalls to Avoid

• Assuming that "more is better" when treating psychiatric conditions
• Overlooking duplicate mechanisms (two bupropion products in this case)
• Failing to recognize the increased risk of serotonin syndrome with multiple serotonergic agents
• Ignoring the pharmacokinetic interactions that can increase blood levels of medications
• Not considering that symptoms like agitation, confusion, or tremor might be medication side effects rather than worsening of the underlying condition 2

The evidence clearly demonstrates that this four-medication combination presents significant risks without additional benefits, and alternative approaches should be considered to optimize both efficacy and safety.