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Cymbalta Vs. Wellbutrin Xl: Drug Comparison

Compare common side effects, interactions, warnings, and more.

Medical Review byMike Bohl, MD, MBA, MPH, MS, ALMNov 4, 2024

Medication Name

Cymbalta

*image for illustrative purpose only

Wellbutrin XL

*image for illustrative purpose only

Summary

Prescription only

Cymbalta® (duloxetine) is a serotonin-norepinephrine reuptake inhibitor (SNRI) used to treat depression and anxiety by increasing the available levels of serotonin and norepinephrine in the brain, which helps improve mood and relieve pain. Its FDA-approved indications include major depressive disorder (MDD), generalized anxiety disorder (GAD), fibromyalgia, and chronic pain conditions such as diabetic peripheral neuropathy and musculoskeletal pain. Off-label uses may include treatment for stress urinary incontinence and as migraine prevention. Cymbalta is available in capsule form, taken orally. Common side effects include nausea, dry mouth, drowsiness, and dizziness, and it carries a boxed warning for an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults, especially during the initial stages of treatment.

Prescription only

Wellbutrin XL® (bupropion extended-release) is an antidepressant that works by inhibiting the reuptake of dopamine and norepinephrine, helping to improve mood and alleviate symptoms of depression. Its FDA-approved indications include the treatment of major depressive disorder (MDD) and the prevention of seasonal affective disorder (SAD). Off-label uses may include smoking cessation, anxiety, and attention-deficit hyperactivity disorder (ADHD). Wellbutrin XL is available in extended-release tablet form, typically taken once daily. Common side effects include insomnia, dry mouth, constipation, and headache, and it has a boxed warning for an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults during the early stages of treatment.

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Drug Category

Serotonin and norepinephrine reuptake inhibitor (SNRI)

Aminoketone antidepressant

Approved Uses

Cymbalta (duloxetine hydrochloride) is indicated for the treatment of the following conditions:

  • Major depressive disorder (MDD) in adults

  • Generalized anxiety disorder (GAD) in adults and pediatric patients 7 years of age and older

  • Diabetic peripheral neuropathic pain (DPNP) in adults

  • Fibromyalgia (FM) in adults and pediatric patients 13 years of age and older

  • Chronic musculoskeletal pain in adults

Wellbutrin XL (bupropion hydrochloride) is indicated for:

  • Treatment of major depressive disorder (MDD)

  • Prevention of seasonal affective disorder (SAD)

Rx Available

Feeling better is possible

Dosage

  • Typically taken orally once daily

  • Comes in 20 mg, 30 mg, and 60 mg delayed-release capsules

  • Typically taken once daily

  • Comes in 150 mg and 300 mg extended-release tablets

Known Common Side Effects

Most common adverse reactions (≥5% and at least twice the incidence of placebo-treated patients):

Adults:

  • Nausea

  • Dry mouth

  • Sleepiness

  • Constipation

  • Decreased appetite

  • Excessive sweating

Pediatric patients:

  • Decreased weight

  • Decreased appetite

  • Nausea

  • Vomiting

  • Fatigue

  • Diarrhea

Most common adverse reactions are (incidence ≥5%; ≥2× placebo rate):

  • Dry mouth

  • Nausea

  • Insomnia

  • Dizziness

  • Inflammation of the throat

  • Abdominal pain

  • Agitation

  • Anxiety

  • Tremor

  • Fluttering heartbeat

  • Sweating

  • Tinnitus

  • Muscle pain

  • Anorexia

  • Urinary frequency

  • Rash

Interactions & Contraindications

  • Concomitant use of an MAOI antidepressant with Cymbalta is contraindicated

  • Use of Cymbalta within 14 days of stopping an MAOI antidepressant is contraindicated

  • In linezolid- or intravenous methylene blue-treated patients, initiation of Cymbalta is contraindicated

  • Drug interactions: potent inhibitors of CYP1A2, potent inhibitors of CYP2D6

  • Seizure disorder

  • Current or prior diagnosis of bulimia or anorexia nervosa

  • Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, antiepileptic drugs

  • Monoamine oxidase inhibitors (MAOIs)

  • Known hypersensitivity to bupropion or other ingredients of Wellbutrin XL

  • Drug interactions: CYP2B6 inducers, drugs metabolized by CYP2D6, drugs that lower seizure threshold, dopaminergic drugs (levodopa and amantadine), MAOIs

  • Drug-laboratory test interactions: Wellbutrin XL can cause false-positive urine test results for amphetamines

Warnings & Precautions

  • Liver toxicity

  • Postural low blood pressure, falls, and fainting

  • Serotonin syndrome

  • Increased risk of bleeding

  • Severe skin reactions

  • Activation of mania or hypomania

  • Angle-closure glaucoma

  • Seizures

  • Blood pressure increases

  • Inhibitors of CYP1A2 or thioridazine: Avoid co-administration with Cymbalta

  • Low blood sodium: Can occur in association with SIADH

  • Glucose control in diabetes

  • Conditions that slow gastric emptying

  • Sexual dysfunction

  • Pregnancy: Third trimester use may increase risk for symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, tremor, irritability) in the neonate

  • Neuropsychiatric adverse events during smoking cessation

  • Seizure risk

  • High blood pressure

  • Activation of mania/hypomania

  • Psychosis and other neuropsychiatric reactions

  • Angle-closure glaucoma

Mental Health Treatment

Feel-good results

Boxed Warning

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants.

Monitor for worsening and emergence of suicidal thoughts and behaviors.

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants.

Monitor for worsening and emergence of suicidal thoughts and behaviors.

References

*This information is from the label for brand name Cymbalta®. See the Full Prescribing Information for more complete information. Duloxetine, the active ingredient in Cymbalta, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient duloxetine.

*This information is from the label for brand name Wellbutrin XL®. See the Full Prescribing Information for more complete information. Bupropion, the active ingredient in Wellbutrin XL, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient bupropion.

The information provided here is NOT MEDICAL ADVICE and is for informational and educational purposes only. The drug comparison tool does not determine eligibility for medications or treatments provided via the Hims/Hers platform. Consultation with a healthcare provider is required to assess suitability for any medical treatment based on individual health and medical history. All product names and associated trademarks are the property of their respective owners.

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