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Wellbutrin Vs. Zoloft: Drug Comparison

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

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

Medication Name

Wellbutrin SR

*image for illustrative purpose only

Zoloft

*image for illustrative purpose only

Summary

Prescription only

Wellbutrin SR® (bupropion sustained-release) is an antidepressant that works by inhibiting the reuptake of norepinephrine and dopamine in the brain, which helps improve mood and reduce symptoms of depression. Its FDA-approved indication includes the treatment of major depressive disorder (MDD). Off-label uses may include smoking cessation, anxiety, and attention-deficit hyperactivity disorder (ADHD). Wellbutrin SR is available in sustained-release tablet form, typically taken once or twice 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 initial stages of treatment.

Prescription only

Zoloft® (sertraline) is a selective serotonin reuptake inhibitor (SSRI) used to treat mood disorders by increasing available serotonin levels in the brain, which helps improve mood and reduce symptoms of anxiety and depression. Its FDA-approved indications include the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder (PD), post-traumatic stress disorder (PTSD), social anxiety disorder (SAD), and premenstrual dysphoric disorder (PMDD). Off-label uses may include the treatment of eating disorders and generalized anxiety disorder (GAD). Zoloft is available in tablet and oral solution forms, typically taken once daily. Common side effects include nausea, dizziness, insomnia, and sexual dysfunction, and it carries a boxed warning for an increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults, particularly during the initial treatment period.

Online Mental Health

More for your mind

Drug Category

Aminoketone antidepressant

Selective serotonin reuptake inhibitor (SSRI)

Approved Uses

Wellbutrin SR (bupropion hydrochloride) is indicated:

  • For the treatment of major depressive disorder (MDD)

Zoloft (sertraline hydrochloride) is indicated for the treatment of:

  • Major depressive disorder (MDD)

  • Obsessive-compulsive disorder (OCD)

  • Panic disorder (PD)

  • Posttraumatic stress disorder (PTSD)

  • Social anxiety disorder (SAD)

  • Premenstrual dysphoric disorder (PMDD)

Rx Available

Feeling better is possible

Dosage

  • Typically taken orally twice daily

  • Comes in 100 mg, 150 mg, and 200 mg tablets

  • Typically taken orally once daily

  • Comes in 25 mg, 50 mg, and 100 mg tablets and 20 mg/mL oral solution

Known Common Side Effects

Most common adverse reactions (incidence ≥5% and ≥2% more than placebo rate) are:

  • Headache

  • Dry mouth

  • Nausea

  • Insomnia

  • Dizziness

  • Inflammation of the throat

  • Constipation

  • Agitation

  • Anxiety

  • Abdominal pain

  • Ringing in the ears

  • Tremor

  • Fluttering heartbeat

  • Muscle pain

  • Sweating

  • Rash

  • Anorexia

Most common adverse reactions (≥5% and twice placebo) in pooled placebo-controlled MDD, OCD, PD, PTSD, SAD and PMDD clinical trials were:

  • Nausea

  • Diarrhea/Loose stool

  • Tremor

  • Indigestion

  • Decreased appetite

  • Excessive sweating

  • Ejaculation failure

  • Decreased libido

Interactions & Contraindications

  • 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 SR.

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

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

  • Concomitant use of monoamine oxidase inhibitors (MAOIs), or use within 14 days of stopping MAOIs

  • Concomitant use of pimozide

  • Known hypersensitivity to sertraline or excipients

  • Zoloft oral solution only: Concomitant use of disulfiram

  • Drug interactions: protein-bound drugs, CYP2D6 substrates

Warnings & Precautions

  • Neuropsychiatric adverse events during smoking cessation

  • Seizure risk

  • High blood pressure

  • Activation of mania/hypomania

  • Psychosis and other neuropsychiatric reactions

  • Angle-closure glaucoma

  • Serotonin syndrome

  • Increased risk of bleeding

  • Activation of mania/hypomania

  • Seizures

  • Angle closure glaucoma

  • QTc prolongation

  • Sexual dysfunction

  • Pregnancy: Third trimester use may increase risk for persistent pulmonary hypertension and withdrawal in the neonate

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

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients.

Closely monitor for clinical worsening and emergence of suicidal thoughts and behaviors.

References

*This information is from the label for brand name Wellbutrin SR®. 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.

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

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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