Is sleepiness a side effect of Wellbutrin (bupropion)?

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Sleepiness and Bupropion: Side Effect Profile

No, sleepiness is not a common side effect of Wellbutrin (bupropion). In fact, bupropion is considered an "activating" antidepressant that is more likely to cause insomnia than sleepiness.

Bupropion's Effect on Sleep and Alertness

Bupropion is characterized in clinical guidelines as an "activating" antidepressant that typically increases energy levels rather than causing sedation. According to the American College of Physicians guidelines:

  • Bupropion is described as "activating" with "possible rapid improvement of energy level" 1
  • It "should not be used in agitated patients" due to its stimulating properties 1
  • To minimize the risk of insomnia, the second daily dose should be taken before 3 p.m. 1

Comparative Side Effect Profile

When compared to other antidepressants, bupropion stands out for its activating properties:

  • Trazodone is associated with a "higher incidence of somnolence than bupropion" 1
  • Research shows bupropion "induced somnolence to a lower extent than placebo" in clinical trials 2
  • Bupropion has been shown to have the highest incidence of insomnia among second-generation antidepressants 2

Mechanism and Sleep Architecture Effects

Bupropion's effects on sleep architecture help explain why it tends to cause insomnia rather than sleepiness:

  • It increases REM latency (time to first REM sleep) 3, 4
  • It increases REM activity and density during the first REM period 4
  • Unlike many sedating antidepressants, it does not suppress REM sleep 4

Common Side Effects of Bupropion

According to the FDA label, the most common side effects of bupropion include:

  • Trouble sleeping (insomnia)
  • Feeling anxious
  • Stuffy nose
  • Nausea
  • Dry mouth
  • Constipation
  • Dizziness
  • Joint aches 5

The FDA specifically notes: "If you have trouble sleeping, do not take bupropion hydrochloride extended-release tablets (XL) too close to bedtime" 5.

Clinical Implications

For patients experiencing sleepiness while taking bupropion:

  • Consider alternative causes of sleepiness (poor sleep quality due to insomnia, other medications, medical conditions)
  • Evaluate timing of medication administration (taking too late in the day can disrupt sleep)
  • Consider that paradoxical reactions can occur in some individuals
  • Monitor for neuropsychiatric symptoms, as bupropion carries warnings about depression and suicidal ideation 6

Special Considerations

  • Bupropion carries a seizure risk of approximately 0.1%, which increases with certain risk factors 6
  • It is contraindicated in patients with seizure disorders, eating disorders, or during abrupt discontinuation of alcohol or sedatives 6
  • The medication should not be taken with MAOIs due to risk of hypertensive reactions 1

If a patient is experiencing sleepiness on bupropion, this would be considered an unusual reaction that warrants further investigation of other potential causes or consideration of an alternative antidepressant.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Effect of treatment with bupropion on EEG sleep: relationship to antidepressant response.

The international journal of neuropsychopharmacology, 2004

Guideline

Medication Safety and Interactions

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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.

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