Can bupropion (Wellbutrin) cause aggression?

From the Guidelines

Bupropion can potentially cause aggression in some individuals, as evidenced by the need for monitoring for the development or worsening of serious neuropsychiatric issues, including hostility, as noted in the guidelines for its use 1. This medication, commonly prescribed under brand names like Wellbutrin for depression and smoking cessation, affects brain chemicals norepinephrine and dopamine, which can sometimes lead to increased irritability, hostility, or aggressive behavior as side effects. These reactions are relatively uncommon but more likely to occur when starting treatment or adjusting dosages. Patients with certain psychiatric conditions, history of aggression, or substance use disorders may be at higher risk for this side effect. Key points to consider include:

• The importance of monitoring for neuropsychiatric issues, as advised by guidelines 1
• The potential for bupropion to cause hostility or aggression, particularly in vulnerable populations
• The need for healthcare providers to discuss adverse event profiles with patients before selecting a medication, as recommended by the American College of Physicians 1 If you experience unusual anger, hostility, or aggressive thoughts while taking bupropion, it's crucial to contact your healthcare provider immediately rather than stopping the medication abruptly. Your doctor might recommend dosage adjustments, switching medications, or additional monitoring. The mechanism behind this side effect likely relates to bupropion's stimulant-like properties and its effects on catecholamine neurotransmitters, which regulate mood and behavior. Most patients tolerate bupropion well, but being aware of all potential side effects helps ensure safe and effective treatment.

From the FDA Drug Label

Advise the patient to read the FDA-approved patient labeling (Medication Guide) Suicidal Thoughts and Behaviors Instruct patients, their families, and/or their caregivers to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Although bupropion hydrochloride extended-release tablets (XL) are not indicated for smoking cessation treatment, it contains the same active ingredient as ZYBAN which is approved for this use Inform patients that some patients have experienced changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation and suicide when attempting to quit smoking while taking bupropion

Aggression is listed as a potential symptom that patients should be alert to when taking bupropion. Patients should be instructed to report any symptoms of aggression to their prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. 2

From the Research

Bupropion and Aggression

• There is evidence to suggest that bupropion can cause aggression, particularly when combined with alcohol 3.
• A study published in 2011 reported a case of a healthy individual who experienced aggressive behavior after taking bupropion and consuming alcohol 3.
• However, other studies have not found a significant link between bupropion and aggression 4, 5, 6, 7.
• It is worth noting that bupropion can have varying effects on individuals, and more research is needed to fully understand its potential impact on aggression.

Mechanism of Action

• Bupropion works by inhibiting the reuptake of noradrenaline and dopamine, which can affect emotional processing and reward processing 4.
• A study published in 2018 found that bupropion can reduce negative biases in emotional processing, but may initially exacerbate impaired reward processing 4.
• However, the relationship between bupropion's mechanism of action and aggression is not fully understood and requires further research.

Clinical Implications

• Bupropion is generally well-tolerated and has a low risk of sexual dysfunction and weight gain 5, 6.
• However, the potential risk of aggression, particularly when combined with alcohol, should be considered when prescribing bupropion 3.
• Clinicians should carefully monitor patients taking bupropion for any signs of aggression or other adverse effects.