iv. Liver function changes

• Long-term or high-dose Wellbutrin is associated with rare liver side effects, occurring in more than 1% of patients taking bupropion. 
• Prolonged use can put more stress on the liver; if the liver becomes overworked or sensitive to medication, this may result in inflammation or decreased liver function, leading to symptoms like jaundice, persistent fatigue, or dark urine. These symptoms can indicate liver damage and should not be ignored. 
• Licensed doctors usually recommend regular blood tests to monitor kidney function over time, especially in patients who already have liver issues or are on higher doses. 

v. Suicidal thoughts 

• Wellbutrin, like antidepressants, can increase the risk of suicidal thoughts or behavior, especially among young people, adolescents, and adults during the first few weeks of treatment. That’s why it’s crucial to read the FDA label and warning before taking medication.
• The exact cause is unknown, but it is early in treatment. Wellbutrin can increase energy and restlessness more quickly than it improves mood, which may temporarily heighten suicidal thinking. 
• Symptoms of suicidal thoughts or behavior can include.

1. Frequent thoughts of death
2. Increased anger
3. Making a plan to harm themself
4. Unusual irritability 

vi. Psychological and cognitive effects 

• Wellbutrin (bupropion) affects cognitive and psychological processes by increasing alertness, norepinephrine, and dopamine, while many people experience improved focus, alertness, and motivation. Some may develop anxiety, agitation, restlessness, or insomnia, blunt emotions, and low feelings, particularly when starting treatment or increasing the dose.
• Rare but serious side effects can include mood swings, irritability, worsening depression, delusions, hallucinations, paranoia, confusion, or problems with concentration. 
• Wellbutrin can also worsen bipolar disorders by triggering manic or hypomanic episodes.

vii. Ophthalmic risk

• Angle-closure glaucoma is a rare but serious eye condition that can be triggered by Wellbutrin in susceptible individuals. 
• Patients younger than 50 on bupropion had twice the risk of angle closure glaucoma.
• It occurs when the drainage angle in the eye becomes blocked, resulting in a sudden increase in eye pressure, which can damage the optic nerves and cause vision loss.

• Symptoms may include eye pain, halos around lights, headaches, nausea, or blurred vision.
• People with a history of narrow-angle or angle-closure glaucoma should use caution when taking Wellbutrin.

viii. Tachyphylaxis (poop-out effect)

• Wellbutrin can cause a long-term effect called tachyphylaxis, or the poop-out phenomenon, where the medication slowly stops working after 12+ months of use. With time, the brain may downregulate dopamine receptors and adjust norepinephrine pathways, reducing the drug’s overall impact.
• As a result, old depressive symptoms such as low mood, fatigue, loss of mood, and loss of motivation can gradually return even if the person continues taking the same dose. This effect most often appears between the 1- and 2-year mark of continuous treatment. 

ix. Tachycardia (Persistent Elevated Heart Rate)

• Wellbutrin may cause tachycardia, a mild but persistent increase in resting heart rate, usually around 5-10 beats per minute, as noted on the FDA and NIH medication safety.
• In most otherwise healthy people, this change is harmless, but it may cause noticeable palpitations or heightened awareness of heartbeat, which some may confuse with anxiety. This effect can persist over long use because Wellbutrin boosts norepinephrine activity. While not usually dangerous, those with existing cardiac issues or sensitivity to stimulants may feel these symptoms more strongly.

Who Is More Likely to Experience Long-Term Side Effects of Wellbutrin? 7 Risks

While Wellbutrin (bupropion) is generally considered safe, certain people have a higher risk of suffering from long-term or persistent side effects. Among them are:

1. People with uncontrolled high blood pressure

2.  Individuals with eating disorders

3. People taking other medications that affect the brain, especially stimulants (e.g., ADHD meds) and other antidepressants. 

4. Long-term smokers or those with liver problems

5. People with a history of seizures

6. Older adults.

7. People sensitive to dopamine/norepinephrine changes

Managing Long-Term Side Effects and Safe Usage of Wellbutrin

Before focusing on how to deal with long-term side effects, it’s crucial to understand that every individual responds to Wellbutrin differently. While many people tolerate the medication well, others may develop side effects over time because of dosage adjustments, underlying health issues, or combinations with other medicines. Knowing how to address these changes early might minimize issues and help you stay on track with therapy.

i. Dose and Formulation

Side effects can often be reduced by modifying the dose or changing the formulation. Your doctor from the therapy fleet may decide to switch you between the IR, SR, or XL versions of Wellbutrin to find the most comfortable option.

ii. Healthy Lifestyle Support

Healthy lifestyle choices, including exercise, proper nutrition, good sleep habits, and stress management, often boost the benefits of Wellbutrin and help reduce unwanted side effects.

iii. Regular Medical Follow-Ups

Ongoing monitoring with BP checks, periodic liver tests, mental health check-ins, and medication reviews keeps long-term Wellbutrin use safe. These follow-ups help your provider adjust treatment when needed.

iv. Stay in Touch With Your Doctor

Keep your healthcare provider informed about any new or worsening side effects, and never discontinue Wellbutrin without medical guidance.

v. Avoid Alcohol

Combining alcohol with Wellbutrin may lower your seizure threshold, making seizures more likely, so it is strongly advised to avoid alcohol during treatment.