Bupropion vs SSRIs: How the Labels Differ

Two different kinds of antidepressant

The National Institute of Mental Health (NIMH) lists SSRIs and norepinephrine-dopamine reuptake inhibitors (NDRIs) among commonly prescribed antidepressants. Sertraline and escitalopram are SSRIs. The bupropion label calls it an aminoketone antidepressant.

This guide uses sertraline and escitalopram as SSRI examples and the Wellbutrin XL label for bupropion. Comparing them shows real, documented differences. It cannot tell you which one would suit you, because a label does not know your history.

How each is thought to act

The sertraline label says it increases serotonin activity in the central nervous system by blocking serotonin reuptake. The bupropion label says its mechanism is unknown, as with other antidepressants, and is presumed to involve norepinephrine, dopamine or both. It describes bupropion as a relatively weak inhibitor of norepinephrine and dopamine reuptake, and says it does not inhibit the reuptake of serotonin.

Approved uses differ

Each medicine here is listed with the uses on its own FDA label. Any other use would be off-label, and that is a conversation with a prescriber.

• Bupropion extended-release (Wellbutrin XL): major depressive disorder, and prevention of seasonal affective disorder.
• Bupropion sustained-release (Wellbutrin SR): major depressive disorder. Forms of a medicine can have different labeled uses.
• Sertraline (Zoloft): six uses, including major depressive disorder, plus OCD, panic disorder, PTSD, social anxiety disorder and premenstrual dysphoric disorder (PMDD).
• Escitalopram (Lexapro): two uses, depression (adults and ages 12 and up) and generalized anxiety disorder (adults and ages 7 and up).

The seizure warning and other bupropion warnings

The main difference on the labels is seizure risk. The bupropion label says it can cause seizures, and that the risk is related to dose and to personal factors, situations and other medicines that lower the seizure threshold. If a person has a seizure on it, the label says to discontinue it and not restart.

The bupropion label also warns about elevated blood pressure, and says to assess blood pressure before and during treatment. It warns of psychosis and other neuropsychiatric reactions and of severe allergic reactions.

SSRI warnings and shared warnings

The sertraline and escitalopram labels warn about serotonin syndrome, a rare but possibly life-threatening reaction, particularly when combined with other serotonin medicines. They also warn of increased bleeding risk, especially with aspirin, NSAID pain relievers, or blood thinners, and of low sodium and symptoms after stopping. These warning sections do not appear in the same way on the bupropion label.

Some warnings appear on both. The boxed warning says antidepressants increased the risk of suicidal thoughts and behaviors in children, teens and young adults, and that all patients should be watched closely. Both also warn about activation of mania and angle-closure glaucoma, and both must not be combined with MAOIs. If you are in crisis, call or text 988, or call 911. Locascio Wellness does not provide emergency services.

Common side effects on each label

Sexual side effects appear in the SSRI lists, and they are not among the most common listed for bupropion extended-release. These lists come from separate studies, so they are not a direct comparison. Do not stop or change a medicine on your own: the bupropion label gives steps for reducing the dose, and the sertraline label says to reduce gradually where possible.

• Bupropion extended-release: dry mouth, nausea, insomnia, dizziness, sore throat, stomach pain, agitation, anxiety, tremor, pounding heartbeat, sweating, ringing in the ears, muscle pain, loss of appetite, frequent urination and rash.
• Sertraline: mostly stomach and gut effects (nausea, loose stool, indigestion, less appetite), plus tremor, sweating and sexual effects. The label has a separate warning about sexual dysfunction.
• Escitalopram: sleep changes in both directions (insomnia, sleepiness), tiredness, nausea, more sweating, and sexual effects on drive, ejaculation and orgasm.

Talking it through with us

A licensed psychiatrist on our team, a Doctor of Osteopathic Medicine with more than three decades of practice, offers online depression treatment by secure video for people physically located in Pennsylvania or New York during each visit. Whether either kind of medicine is an option for you is a decision for you and your prescriber. Ask us whether our psychiatrist can help, using our medication care contact form.

Our therapists do not prescribe. They see clients in Pennsylvania, West Virginia, Arizona, Colorado and Florida, not New York.