Bupropion (Wellbutrin) Patient Guide: Benefits, Dosing, and Side Effects Explained

Table of Contents

This guide is adapted from the clinician guide authored by Sebastián Malleza, M.D., M.Sc. at the Psychopharmacology Institute. For the complete clinical resource, visit: Bupropion Guide: Pharmacology, Indications, Dosing Guidelines and Adverse Effects

What is Bupropion?

Bupropion (brand names include Wellbutrin, Wellbutrin SR, Wellbutrin XL, and others) is a medication used to treat major depressive disorder (MDD)[15]. It works differently from many other antidepressants because it affects norepinephrine and dopamine instead of serotonin[1]. Bupropion may be particularly helpful for people experiencing depression with fatigue, poor concentration, or lack of enjoyment in activities[5,16,17].

The medication is also FDA-approved for:

  • Preventing seasonal affective disorder (SAD) – Wellbutrin XL only[19]
  • Helping people quit smoking – generic SR formulation[22]

How Does This Medication Work?

Bupropion works by increasing levels of two important brain chemicals[1]:

  • Norepinephrine: Helps regulate mood, energy, and attention
  • Dopamine: Involved in motivation, pleasure, and reward

Unlike most other antidepressants, bupropion does not affect serotonin levels[2]. This unique mechanism may explain why it:

  • Has a lower risk of sexual side effects compared to other antidepressants[1,3]
  • Does not typically cause weight gain[1,3]
  • May help with energy and motivation[5]

How to Take This Medication

Bupropion comes in three different formulations, each taken differently:

Extended-Release (XL) – Once Daily

This is the preferred formulation for most patients[7,14]

  • Tablets: 150 mg, 300 mg, 450 mg
  • Take once in the morning with or without food
  • Swallow whole – do not crush, chew, or split

Sustained-Release (SR) – Twice Daily

  • Tablets: 100 mg, 150 mg, 200 mg
  • Take twice daily with at least 8 hours between doses
  • Swallow whole – do not crush, chew, or split

Immediate-Release – Three to Four Times Daily

  • Tablets: 75 mg, 100 mg
  • Take 3-4 times daily with at least 6 hours between doses
  • Rarely used due to inconvenient dosing schedule

Important instructions:

  • Take at the same time(s) each day
  • Morning dosing may help prevent sleep problems
  • If you miss a dose, take it as soon as you remember unless it’s close to your next dose. Never double up on doses
  • The tablet shell may appear in your stool – this is normal and doesn’t affect the medication

Typical Dosing

For Depression (Extended-Release XL)

  • Starting dose: 150 mg once daily in the morning
  • After 4 days: May increase to 300 mg once daily
  • Maximum dose: 450 mg once daily

For Seasonal Affective Disorder Prevention (XL only)

  • Start in autumn before symptoms begin
  • Initial dose: 150 mg once daily
  • After 7 days: May increase to 300 mg once daily
  • Continue through winter, then taper in spring

For Smoking Cessation (SR formulation)

  • Start 1 week before quit date
  • Days 1-3: 150 mg once daily
  • Day 4 onward: 150 mg twice daily
  • Continue for at least 12 weeks after quitting

Common Side Effects

Many side effects improve as your body adjusts to the medication.

Most Common Side Effects

Sleep and Mood Effects:

  • Insomnia or trouble sleeping (11-40%)[7]
    • Taking medication in the morning can help
    • Usually improves with continued treatment[42,43]
  • Agitation or anxiety (2-32%)[10,44]
    • Despite this, studies show bupropion helps anxiety symptoms in depression as much as SSRIs[45]
    • More common in first few weeks[43]

Physical Effects:

  • Headache (up to 34%)
  • Dizziness (6-22%)
  • Tremor or shaking (1-21%)
  • Dry mouth (10-28%)
  • Excessive sweating (5-22%)[10,50]

Digestive Effects:

  • Nausea/vomiting (9-23%)
    • Taking with food may help[47]
    • Usually temporary[1,42]
  • Constipation (8-26%)[10]
  • Weight loss (14-28%)
    • More common than with other antidepressants[48]
    • May be beneficial if weight gain is a concern
    • Tell your doctor if you’re losing too much weight

Heart-Related Effects:

  • Fast heartbeat (11%)
  • Increased blood pressure (2% in some studies)
    • Risk higher when combined with nicotine replacement[10]

Important Safety Information

Do Not Take Bupropion If:

  • You have or have had seizures or epilepsy[1]
  • You have an eating disorder (especially bulimia or anorexia)
  • You are taking or have recently taken (within 14 days) MAO inhibitors
  • You are abruptly stopping alcohol or sedatives
  • You are taking other forms of bupropion

Talk to Your Doctor Before Taking Bupropion If You Have:

  • Head injury or brain tumor
  • Heavy alcohol use
  • Liver problems
  • Kidney problems
  • High blood pressure
  • Diabetes
  • Glaucoma[10,57]
  • History of drug or alcohol misuse[60-63]

Important Drug Interactions

Bupropion can interact with many medications. Tell your doctor about all medications you take, especially:

  • Other antidepressants (particularly venlafaxine, duloxetine, or vortioxetine)
  • Antipsychotics
  • Beta-blockers like metoprolol
  • Tamoxifen
  • Medications for Parkinson’s disease[10]

Avoid While Taking Bupropion:

  • Alcohol (can increase seizure risk)
  • Diet pills or other stimulants
  • Other forms of bupropion
  • Driving or operating machinery until you know how it affects you

When to Contact Your Doctor Immediately

Contact your healthcare provider right away if you experience:

  • Seizure or convulsion
  • Severe agitation or panic attacks
  • Thoughts of suicide or worsening depression
  • Hallucinations or paranoid thoughts[56]
  • Severe allergic reaction: rash, hives, swelling, trouble breathing[58]
  • Eye pain or vision changes[10,57]
  • Rapid or irregular heartbeat
  • Severe headache or confusion

Seizure Risk – Important Information

Bupropion has a higher risk of causing seizures compared to other antidepressants[55]. The risk increases with:

  • Higher doses (especially over 450 mg/day)[10]
  • Immediate-release formulation
  • Eating disorders
  • Head injury
  • Alcohol withdrawal
  • Other medications that lower seizure threshold

To reduce seizure risk:

  • Take exactly as prescribed
  • Do not exceed recommended doses
  • Use extended-release formulation when possible[7]
  • Avoid alcohol

Starting and Stopping the Medication

Starting:

  • It may take 4-6 weeks to feel the full benefits
  • Side effects often improve after the first 1-2 weeks
  • Take consistently as prescribed, even if you don’t feel different right away

Stopping:

  • Do not stop suddenly without talking to your doctor
  • While bupropion has fewer withdrawal symptoms than some antidepressants, gradual tapering is still recommended
  • Your doctor will create a tapering schedule for you

Special Considerations

Pregnancy and Breastfeeding

  • Studies have not shown increased birth defects with bupropion use during pregnancy[64,65]
  • Bupropion passes into breast milk in small amounts (~2% of maternal dose)[74]
  • Discuss risks and benefits with your doctor if you are pregnant, planning pregnancy, or breastfeeding

Older Adults

  • No routine dose adjustment needed
  • May need closer monitoring[78]
  • Consider starting at lower doses

Liver Problems

  • Requires significant dose reduction
  • Your doctor will adjust your dose based on severity[10]

Kidney Problems

  • May need dose reduction if you have moderate to severe kidney disease[77]

Weight Considerations

  • If you are significantly overweight (BMI ≥35), the medication may stay in your system longer[79]
  • Tell your doctor if you have obesity

Benefits of Bupropion

Many patients choose bupropion because it:

  • Has minimal sexual side effects compared to SSRIs[1,3]
  • Does not cause weight gain (may cause modest weight loss)[48]
  • May improve energy and motivation[5,16]
  • Can help with concentration[17]
  • Is effective for seasonal depression prevention[19]
  • Can help with smoking cessation[22]

Important Notes

  • Bupropion may cause false-positive drug tests for amphetamines[11,12]
  • The medication has been misused by some people, particularly in correctional facilities[60-63]
  • Never crush or snort tablets – this is dangerous and can cause seizures[63]

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Disclaimer: This guide is for general informational purposes and is not a substitute for professional medical advice. Always discuss any questions about your medication with your healthcare provider.

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