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Wellbutrin XL side effects and how to avoid them

The most common Wellbutrin XL side effects aren’t severe and may resolve within a couple of weeks
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Key takeaways

  • Wellbutrin XL is an antidepressant that mainly causes temporary side effects like headaches, weight loss, and nausea, which typically improve over time.

  • Serious side effects of Wellbutrin XL are rare but can include a skin rash, anxiety, and angle-closure glaucoma.

  • To minimize Wellbutrin XL side effects, it’s recommended to provide a complete medical history to the prescriber, take the medication as directed, and monitor for any serious reactions requiring medical attention.

Wellbutrin XL is a brand-name antidepressant approved to treat symptoms of depression in adults. The generic version of Wellbutrin XL is bupropion hydrochloride (HCl) extended-release (ER). Like Wellbutrin SR, Wellbutrin XL blocks the reuptake of norepinephrine and dopamine in the brain to alleviate symptoms of depression. The main difference between Wellbutrin SR and Wellbutrin XL is their standard dosage. Wellbutrin XL is an extended-release medication that is taken once daily, while Wellbutrin SR is a sustained-release medication that is taken twice daily. They share similar side effects.

Common side effects of Wellbutrin XL

The most common side effects of Wellbutrin XL are headache, weight loss, dry mouth, trouble sleeping, nausea, dizziness, constipation, fast heartbeat, and sore throat, according to the National Alliance on Mental Illness (NAMI). These side effects tend to resolve within the first two weeks of starting the medication.

Serious side effects of Wellbutrin XL

Serious side effects of Wellbutrin XL are rare. According to NAMI, less than 10% of patients experience the following serious side effects:

Wellbutrin XL and weight loss

Weight loss is a common side effect of Wellbutrin XL. In clinical trials of Wellbutrin SR, 28% of patients who took 300 mg or 400 mg per day lost more than five pounds. Appetite loss is also another significant side effect. The stimulant qualities of bupropion may also contribute to weight loss. 

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Although it is generally safe to take Wellbutrin XL for weight loss, it may not be safe for patients with a diagnosis of an eating disorder or a seizure disorder, patients taking monoamine oxidase inhibitors (MAOIs), or those with a known allergic reaction to bupropion HCl. 

How soon do Wellbutrin XL side effects start?

Many common side effects of Wellbutrin XL are experienced early in treatment, sometimes after the first dose. These side effects include headache, dry mouth, agitation, nausea, dizziness, and diarrhea (constipation may happen a little more delayed as well). Some side effects may take a few days or weeks to manifest. Weight changes may take several weeks or months before they’re noticed. Most of the serious side effects of Wellbutrin XL are delayed side effects, but severe allergic reactions, including airway closure, can happen within minutes of taking the first dose.

How long do Wellbutrin XL side effects last?

Bupropion breaks down into active drugs, so the half-lives of both bupropion and its active metabolites are 24 to 72 hours. That means that it will take at least a week for the body to clear out a dose of bupropion and its active metabolites from the bloodstream.

Research has shown that side effects of bupropion usually correspond to the times when the drug’s concentration peaks in the bloodstream. This will only happen once per day with Wellbutrin XL, so side effects should improve as the day goes on. 

As with all drugs, many of the common side effects of Wellbutrin XL, such as nausea, headache, or sleeping problems, may improve after the drug has been taken for a few days or weeks. In a 52-week study, researchers found that people experienced fewer side effects the longer the treatment continued. 

What are the long-term side effects of Wellbutrin XL?

Most side effects of Wellbutrin XL are temporary. They will go away during treatment or, if not, when the drug is discontinued. The only side effect associated with long-term use of Wellbutrin XL is weight changes.

Wellbutrin XL interactions

As with many drugs that affect the brain, Wellbutrin has several drug interactions. Most of these drug interactions are minor, but some drug combinations are risky and may require avoiding certain medications, changing dosages, or carefully watching for side effects. 

Because of serious side effects, the following drugs should never be taken with Wellbutrin XL:

  • Monoamine oxidase inhibitors (MAOIs), such as phenelzine, selegiline, and linezolid
  • The antipsychotic drugs pimozide and thioridazine

Wellbutrin should also not be taken when discontinuing certain medicines, such as:

People taking Wellbutrin XL should avoid drinking alcohol or drink as little as possible. The combination could bring on psychiatric disorders. Wellbutrin XL should not be taken by someone experiencing alcohol withdrawal. 

Because of the potential risk of seizures, people taking Wellbutrin XL with drugs that lower the seizure threshold have to be monitored carefully. These medications include: 

Bupropion can slow down the body’s metabolism of other drugs, increasing the risk of side effects caused by them. Dosages of bupropion or these other drugs may need modification.

Another potential problem involves drugs that raise dopamine levels. Increasing dopamine is one of the effects of bupropion, so the combination of dopamine-increasing medications and bupropion might increase dopamine in the brain to dangerous levels. 

Safety measures while using Wellbutrin XL

While it is an effective drug, there are some safety considerations to keep in mind when taking Wellbutrin XL:

  • Children, teens, and young adults: The Food and Drug Administration (FDA) has not approved Wellbutrin XL for anyone younger than 18 years of age. Wellbutrin XL has a boxed warning from the FDA about the possibility of it causing suicidal thoughts and behaviors in children, adolescents, and young adults. People younger than 25 years of age should be carefully watched by parents, caregivers, or loved ones for worsening depression or suicidality when taking Wellbutrin XL.
  • Breastfeeding or pregnancy: Women who are breastfeeding should be cautious about taking Wellbutrin XL. The drug is present in breast milk, but so far, there’s no evidence that it can affect a nursing baby. There is also no evidence that Wellbutrin XL causes problems to a developing fetus or adverse effects during pregnancy. As with any medication, though, the benefits and risks of Wellbutrin XL should still be evaluated by a healthcare professional if you are planning to or have become pregnant. 
  • Liver or kidney problems: Doses may need to be reduced in people with liver or kidney disease. 
  • Bipolar disorder: Anyone with bipolar disorder must be cautious when taking antidepressants like Wellbutrin XL. Antidepressants can trigger manic episodes in people with bipolar disorder.
  • Tic disorders: People who have tic disorders, including Tourette’s syndrome, may find that their tic disorders worsen while taking bupropion.
  • High blood pressure: Wellbutrin XL can raise blood pressure, so people being treated for hypertension or who have had a recent heart attack will require closer monitoring when taking Wellbutrin. They may be asked to check their blood pressure regularly.
  • Risk of abuse: Although the FDA does not consider Wellbutrin XL to be a drug that can cause physical dependence, withdrawal, or abuse, it is sometimes used as a street drug because of its stimulant qualities. Taking too much of the drug could cause serious side effects, such as seizures. 

Contact Poison Control or go to an emergency department if you take too much Wellbutrin XL. There is a risk of severe side effects, such as seizures. Other symptoms of an overdose include loss of consciousness, racing heartbeat, irregular heartbeat, and hallucinations. A Wellbutrin overdose can be particularly dangerous if other drugs are taken, too. Some people have died from overdosing on Wellbutrin. 

How to avoid Wellbutrin XL side effects

1. Make sure your prescriber has a complete medical history. 

Wellbutrin XL can make some medical conditions worse. It can also interact with a wide variety of drugs. Make sure your prescriber has a complete medical history and knows about all the prescription drugs, over-the-counter (OTC) medications, and supplements that you’re taking.

2. Take Wellbutrin XL as directed. 

Take Wellbutrin XL as instructed. The typical dose is 300 mg per day, but the starting dose may be 150 mg per day. Wellbutrin can be taken with a meal or on an empty stomach.

3. Take Wellbutrin XL in the morning.

Side effects of Wellbutrin XL typically occur when the drug levels in the blood are at their peak. Take the daily pill as early as possible in order to minimize side effects and avoid difficulty sleeping at night.

4. Don’t take a missed dose.

If a dose is missed, skip it. Take the next dose as scheduled. Do not take extra medicine to make up for a missed dose.

5. Don’t stop taking Wellbutrin XL without talking to your prescriber.

When it’s time to stop taking Wellbutrin, a healthcare provider may prescribe a smaller dose of 150 mg per day. Sudden discontinuation of Wellbutrin can produce new symptoms.

How to treat side effects of Wellbutrin XL

Many of the common side effects of Wellbutrin XL can be managed with OTC medications or home remedies, but serious side effects will require immediate medical attention: 

  • Insomnia: If you have trouble sleeping, take the pill as early as possible in the morning. Practice good sleep hygiene at night. If insomnia persists, talk to the prescriber about possibly lowering the dose or changing the dosage form. Taking the SR or IR formulation at an earlier scheduled time may help. 
  • Headaches: Headaches can be treated with OTC pain relievers, such as ibuprofen or acetaminophen. If Wellbutrin XL is causing migraine headaches, talk to your prescribing healthcare provider.
  • Nausea and vomiting: OTC nausea remedies or dietary changes may help reduce nausea and vomiting, but if symptoms don’t improve within a few weeks, talk to your prescriber.
  • Weight changes: If your weight increases or decreases while taking Wellbutrin XL, talk to your prescriber. Dietary and lifestyle adjustments are usually enough to fix this side effect.
  • Hypertension: If blood pressure increases, immediately inform your prescriber. 
  • Suicidality: Immediately call your prescriber or other healthcare professional if depression symptoms worsen or there is an increased risk of suicide.
  • Seizures: If seizures are experienced, call your prescribing healthcare professional. The prescriber may permanently discontinue Wellbutrin XL or switch it to a lower dose.
  • Allergic reactions: Wellbutrin XL should be stopped at any sign of an allergic reaction or skin reaction. Immediate medical help may be needed if the symptoms are severe. The drug may have to be discontinued if it is determined to be the cause.

Expert takeaway 

“Wellbutrin XL can be a safe and effective treatment for depression under the right circumstances,” says Josephine Bawab, Pharm.D., member of the SingleCare Medical Board. “It is important to weigh the risks and benefits of taking it with a healthcare provider before starting it.”  

Bottom line: Is Wellbutrin XL safe?

Wellbutrin has a long track record. Adverse effects are commonly experienced, but they tend to be minimal. Clinical experience has shown that side effects improve the longer the drug is taken. Serious side effects are rare, but they are more likely to occur if certain medical conditions are present or certain medications are taken as well. Bupropion is considered to have a low risk of drug abuse and dependence, but people have been known to abuse it and may hurt themselves by taking too much. In summary, Wellbutrin XL can be considered safe as long as people take certain precautions and watch for warning signs. If you have any doubts, get medical advice about the pros and cons of Wellbutrin from a mental health professional.

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