What is the correlation between bupropion (Wellbutrin) and patients with a history of substance use disorder?

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Last updated: March 10, 2025 • View editorial policy

From the Guidelines

Bupropion (Wellbutrin) should be used with caution in patients with a history of substance use disorder, as it may lower the seizure threshold and trigger cravings or psychological associations with previous drug use, although some studies suggest it may help reduce cravings in certain cases. When considering the use of bupropion in patients with a history of substance use disorder, it is essential to weigh the potential benefits against the risks. According to a study published in 2022 1, bupropion may be beneficial for patients with a history of substance use disorder, particularly those with depression, as it has been shown to be effective in reducing depressive symptoms. However, the study also notes that bupropion may lower the seizure threshold, which is a concern for patients with a history of seizures or substance use disorder.

Some key considerations when using bupropion in patients with a history of substance use disorder include:

  • Monitoring for signs of seizure activity, particularly in patients with a history of seizures or substance use disorder
  • Implementing more frequent follow-ups and drug screening when appropriate
  • Developing clear contingency plans for patients with substance use history taking bupropion
  • Being aware of the potential for bupropion to trigger cravings or psychological associations with previous drug use, particularly in patients with a history of stimulant addiction
  • Considering alternative treatments, such as mutual help meetings or medically supervised withdrawal, for patients with more severe substance use disorders

It is also important to note that bupropion has a lower risk of abuse compared to some other antidepressants, but special monitoring is still warranted in those with substance use history. The standard dosing of bupropion begins at 150 mg daily for 3-7 days, potentially increasing to 150 mg twice daily if tolerated, with a maximum recommended dose of 450 mg daily divided into multiple doses. Side effects that might be confused with withdrawal or trigger relapse include insomnia, agitation, and anxiety. Overall, the use of bupropion in patients with a history of substance use disorder requires careful consideration and monitoring to minimize the risks and maximize the benefits.

From the FDA Drug Label

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance Bupropion is not a controlled substance.

  1. 2 Abuse Humans Controlled clinical studies of bupropion HCl immediate-release conducted in normal volunteers, in subjects with a history of multiple drug abuse, and in depressed patients demonstrated an increase in motor activity and agitation/excitement In a population of individuals experienced with drugs of abuse, a single dose of 400 mg bupropion produced mild amphetamine-like activity as compared to placebo on the Morphine-Benzedrine Subscale of the Addiction Research Center Inventories (ARCI), and a score intermediate between placebo and amphetamine on the Liking Scale of the ARCI These scales measure general feelings of euphoria and drug desirability. Findings in clinical trials, however, are not known to reliably predict the abuse potential of drugs Nonetheless, evidence from single-dose studies does suggest that the recommended daily dosage of bupropion when administered in divided doses is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers. However, higher doses (that could not be tested because of the risk of seizure) might be modestly attractive to those who abuse CNS stimulant drugs

The correlation between bupropion (Wellbutrin) and patients with a history of substance use disorder is that bupropion may have some abuse potential, particularly at higher doses.

  • Key findings include: + Increased motor activity and agitation/excitement in subjects with a history of multiple drug abuse + Mild amphetamine-like activity in individuals experienced with drugs of abuse + Potential for modest attraction to those who abuse CNS stimulant drugs at higher doses However, the recommended daily dosage of bupropion is not likely to be significantly reinforcing to amphetamine or CNS stimulant abusers [2] [3].

From the Research

Correlation between Bupropion and Substance Use Disorder

  • Bupropion, an antidepressant, has been found to have addictive potential due to its structural similarities with psychostimulants 4.
  • Several case reports have been published addressing its misuse, mainly through nasal insufflation and intravenous administration, with most cases citing a history of substance use disorder 4.
  • A study found that bupropion can also be misused by chewing, even at high doses, and can lead to a substance use disorder 4.
  • The use of bupropion in various indications for treating mental disorders, along with its over-the-counter accessibility and lower risk of stigmatization, could increase the prevalence of bupropion misuse 4.

Risk Factors and Interactions

  • Bupropion has been found to be a common cause of drug-related new-onset generalized seizures, particularly in patients with a history of attention deficit disorder, bulimia, and previous heavy alcohol use 5.
  • 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.
  • Bupropion has inhibitory effects on cytochrome P450-2D6 (CYP2D6), which can lead to clinically relevant drug interactions 7.

Treatment Considerations

  • Depression and substance use disorders are highly comorbid conditions, and evidence suggests that treating both conditions simultaneously can lead to the best outcome 8.
  • Practitioners should be aware of treatment recommendations for patients with co-occurring depression and substance use disorders, potential antidepressant interactions with alcohol and drugs of abuse, and the risk of misuse of antidepressants 8.
  • Bupropion has been found to be effective in helping people quit tobacco smoking, but its use in patients with a history of substance use disorder requires careful consideration of the potential risks and benefits 7, 8.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.