Does concomitant use of bupropion (Wellbutrin) and dextroamphetamine/amphetamine (Adderall) increase the risk of seizures?

From the Guidelines

There is no direct evidence from recent high-quality studies to confirm that taking Wellbutrin with Adderall increases seizure risk, but caution is advised due to the potential for both medications to lower the seizure threshold individually. Both Wellbutrin (bupropion) and Adderall (amphetamine salts) have properties that can affect seizure risk. Wellbutrin carries a dose-dependent seizure risk, particularly at doses above 450mg daily 1, while Adderall's stimulant properties can also potentially trigger seizures in susceptible individuals.

Key Considerations

• The combination of these medications should be approached with caution, especially in patients with pre-existing seizure disorders, history of head trauma, eating disorders, or those taking other medications that lower seizure threshold.
• If this combination is necessary for treating conditions like depression with ADHD, healthcare providers typically start with lower doses of both medications and gradually increase while monitoring for adverse effects 1.
• Patients should ensure their doctor knows about all medications they're taking, stay well-hydrated, avoid alcohol, maintain regular sleep patterns, and report any unusual symptoms like confusion, muscle twitching, or loss of consciousness immediately.

Important Factors

• The risk varies between individuals based on personal medical history and other factors, so medical supervision is essential when taking these medications together.
• As noted in the practice parameter for the use of stimulant medications, a thorough medical history of the patient and first-degree family members is crucial before initiating such a combination 1.
• Although there are no studies of the combination of bupropion and stimulants in the treatment of ADHD or other psychiatric conditions, clinicians should proceed with caution until further studies are available 1.

From the FDA Drug Label

The following conditions can also increase the risk of seizure: concomitant use of other medications that lower the seizure threshold (e.g., other bupropion products, antipsychotics, tricyclic antidepressants, theophylline, and systemic corticosteroids), metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia), or use of illicit drugs (e.g., cocaine) or abuse or misuse of prescription drugs such as CNS stimulants. Drugs that lower seizure threshold: Dose bupropion hydrochloride extended-release tablets (XL) with caution. ( 5.3,7.3)

The use of Adderall, a CNS stimulant, with bupropion (Wellbutrin) may increase the risk of seizure due to the additive effect of both medications lowering the seizure threshold.

• Key points:
  • Bupropion can cause seizure, and the risk is dose-related.
  • Concomitant use of other medications that lower the seizure threshold, such as CNS stimulants, can increase the risk of seizure.
  • It is recommended to dose bupropion with caution when used with drugs that lower seizure threshold 2, 2.

From the Research

Seizure Risk with Wellbutrin and Adderall

• There is limited direct evidence on the combined use of Wellbutrin (bupropion) and Adderall (a stimulant) and its effect on seizure risk 3, 4, 5, 6.
• A study on bupropion found that the observed incidence of seizures with bupropion doses of 450 mg/day or less ranged from 0.35%-0.44% 6.
• Another study found that the risk of seizure appears to be higher with bupropion doses above the recommended maximum, and predisposing factors were noted in over half of the reported cases 6.
• Research on stimulants like methylphenidate (MPH) suggests that they may not be associated with an increased risk of seizures, and may even be associated with a reduced risk of seizures in some cases 3.
• However, there is a lack of studies specifically examining the combination of Wellbutrin and Adderall, making it difficult to draw conclusions about the seizure risk associated with this combination.

Factors Influencing Seizure Risk

• Predisposing factors, such as a history of seizures or certain medical conditions, may increase the risk of seizures with bupropion 6.
• The dose of bupropion may also play a role, with higher doses potentially increasing the risk of seizures 6.
• Individual factors, such as the presence of comorbidities or the use of other medications, may also influence the seizure risk associated with the combination of Wellbutrin and Adderall.

Need for Further Research

• More studies are needed to fully understand the potential risks and benefits of using Wellbutrin and Adderall together, particularly with regards to seizure risk 4, 5.
• Further research should aim to clarify the optimal target population for this combination, as well as the potential long-term outcomes 4, 5.