Wellbutrin alternatives: what to try next and why

Looking for an alternative to Wellbutrin (bupropion)? Maybe the side effects don’t sit right, or it didn’t help your symptoms. There are several proven options that work in different ways. Below I’ll walk you through common drug alternatives, what they tend to do, and simple non-drug strategies you can combine with medication. Use this as a start for a conversation with your prescriber—not a prescription plan.

Common drug alternatives and what sets them apart

SSRIs (selective serotonin reuptake inhibitors) are often the first switch doctors consider. Examples: sertraline (Zoloft), escitalopram (Lexapro), and fluoxetine (Prozac). They help mood, anxiety, and come with a relatively safe track record. Watch for sexual side effects, mild nausea, and sleep changes. Fluoxetine has a longer half-life, so it stays in your system longer after stopping.

SNRIs (serotonin-norepinephrine reuptake inhibitors) like venlafaxine (Effexor) and duloxetine (Cymbalta) can help both depression and certain types of pain. Venlafaxine may raise blood pressure at higher doses; duloxetine is often chosen when pain and mood problems overlap.

Mirtazapine (Remeron) is often used if sleep or appetite are issues—people commonly feel more sleepy and may gain weight. Trazodone is another option used at lower doses mainly for sleep but it can help mood too. Vortioxetine (Trintellix) may help cognitive symptoms and tends to cause fewer sexual side effects.

If your depression is resistant or complicated, doctors sometimes consider MAOIs (like tranylcypromine) or augmentation with atypical antipsychotics (such as aripiprazole or brexpiprazole). These choices come with special rules: MAOIs need dietary caution and washout periods; antipsychotic augmentation needs close monitoring for side effects.

Non-drug choices and safe switching tips

Medication is only one piece. Cognitive behavioral therapy (CBT), regular exercise, consistent sleep, and reducing alcohol or stimulants can all boost response. For some people, combining therapy with a medication switch gives the best results.

Switching meds requires care. Your doctor may suggest tapering, a direct switch, or a washout period depending on the drugs involved. Fluoxetine’s long half-life can shorten withdrawal risk when switching; others may need a short break to avoid interactions. Always follow a prescriber’s plan—abrupt changes can cause withdrawal, mood shifts, or drug interactions.

If you want a quick next step: note the symptoms that bothered you on Wellbutrin (sex drive changes, anxiety, sleep, energy) and share them with your provider. That helps pick the option most likely to improve your specific problems. If you experience severe side effects, suicidal thoughts, or sudden mood changes, seek urgent care right away.

Want links to deeper reads on specific drugs, side effects, or how to switch safely? I can pull the most relevant articles and guides from our site so you can take those notes to your clinician.