Wellbutrin (bupropion) alternatives: What can I take instead of Wellbutrin?

In this article:

• Wellbutrin alternatives
• Trazodone
• Remeron
• Trintellix
• Viibryd
• Lexapro
• OTC antidepressants
• Natural alternatives
• How to switch
• Choosing the right treatment

In this article

• Wellbutrin alternatives
• Trazodone
• Remeron
• Trintellix
• Viibryd
• Lexapro
• OTC antidepressants
• Natural alternatives
• How to switch
• Choosing the right treatment

Wellbutrin is a brand-name prescription drug that treats major depressive disorder (MDD). The extended-release version, Wellbutrin XL, is also FDA-approved to treat seasonal affective disorder (SAD), a type of depression that comes on in certain seasons, like winter. The active ingredient is bupropion hydrochloride, an atypical antidepressant that does not affect serotonin levels, unlike other antidepressant drug classes, but rather works by blocking the reuptake of norepinephrine and dopamine in the brain. Wellbutrin comes in sustained-release and extended-release oral tablets. If Wellbutrin is not effective or side effects are a problem, prescribers have a wide range of alternative antidepressants or drug combinations that may work better.

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What can I take instead of Wellbutrin?

Wellbutrin typically isn’t a first-choice depression treatment. Instead, the American Psychological Association recommends starting with selective serotonin reuptake inhibitors (SSRIs), such as Prozac (fluoxetine), or serotonin-norepinephrine reuptake inhibitors (SNRIs), such as Cymbalta (duloxetine). 

Wellbutrin is typically a second choice when SSRI or SNRI treatment does not work well or side effects are a problem. Wellbutrin has a lower risk of some serious side effects of drugs that increase serotonin activity, particularly serotonin syndrome. However, like other antidepressants, Wellbutrin can, in rare cases, worsen depression and make patients suicidal.

If Wellbutrin is not effective at improving the symptoms of depression, patients can switch back to first-line treatments like SNRI or SSRI antidepressants. Other atypical antidepressants, including trazodone, mirtazapine, Viibryd (vilazodone), and Trintellix (vortioxetine), may be a better option. For some patients—particularly those with other mental health conditions, such as anxiety disorder, or pain—the best treatment may involve less commonly prescribed drugs like tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs). 

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Top 5 Wellbutrin alternatives

The most common treatment options when Wellbutrin or first-line antidepressant medications are not effective are other atypical antidepressants, including:

1. Trazodone

Trazodone is an atypical antidepressant that affects serotonin levels in the brain. Doses are usually taken twice daily. Adverse effects associated with trazodone include drowsiness, dry mouth, headache, dizziness, and weight loss. Trazodone also carries a black box warning that the drug can worsen depression and bring on suicidal thoughts and behavior.

2. Remeron (mirtazapine) 

Remeron is a tetracyclic antidepressant that affects serotonin and norepinephrine levels in the brain. The tablet or orally disintegrating tablet is usually taken once daily at bedtime. The orally disintegrating tablets dissolve in the mouth and can be swallowed with or without liquid.

The most common side effects of Remeron include increased appetite, weight gain, dry mouth, drowsiness, and dizziness. Remeron also carries the boxed warning about worsening depression and suicidal thoughts or behavior.

3. Trintellix (vortioxetine)

Trintellix blocks serotonin reuptake in the brain but also acts like serotonin, increasing the overall serotonin activity in the brain. Doses are taken once daily. The most common adverse effects of Trintellix are digestive system side effects (nausea, diarrhea, constipation, vomiting, flatulence), dry mouth, dizziness, abnormal dreams, itching, and sexual dysfunction. Trintellix also carries a black box warning about worsening depression and suicidal thoughts or behavior.

4. Viibryd (vilazodone)

Viibryd is an antidepressant that works like an SSRI but also imitates serotonin in the brain, so overall serotonin activity is increased. Doses are taken once daily. The most common adverse effects of Viibryd include digestive system complaints (diarrhea, nausea, vomiting, and stomach pain), insomnia, and headache. Viibryd also carries a black box warning about worsening depression and suicidal thoughts or behavior.

5. Lexapro (escitalopram) plus Wellbutrin SR (bupropion sustained-release)

Although the combination of Lexapro and Wellbutrin SR is not approved by the Food and Drug Administration, clinical trials show that this combination can be highly effective in helping people with treatment-resistant depression. The use of both medications impacts the three major neurotransmitters (serotonin, norepinephrine, and dopamine) that are important in the treatment of depression. Although combining Wellbutrin SR and Lexapro has had positive results, it may not be recommended for some because the combination may have too strong an effect, leading to increased physical, mental, or sexual side effects. Wellbutrin SR can cause blood levels of Lexapro to increase, leading to increased side effects of that drug.

Over-the-counter antidepressants

There are no over-the-counter antidepressants. Some over-the-counter dietary supplements and vitamins can complement antidepressant treatment or improve mood in people who feel down. These include St. John’s wort, probiotics, vitamin D, vitamin B12, folate, vitamin B, niacin, magnesium, zinc, calcium, and iron. No over-the-counter medication or supplement can substitute for prescription antidepressants in the treatment of major depressive disorder.

Natural alternatives to Wellbutrin

Antidepressants are effective and often necessary for treating major depressive symptoms. Natural alternatives to Wellbutrin can help, but should not take the place of prescription medications in people diagnosed with major depressive disorder. The most effective nonpharmaceutical treatment for depression is cognitive behavioral therapy (CBT), which helps people change the way they think and react. In addition, exercise, sunlight or light therapy, and diets that include omega-3 fats and tryptophan (e.g., fish, nuts, poultry, and whole grains) can help improve mood. Obtaining medical advice from a healthcare professional before trying any of these alternatives is important. 

How to switch to a Wellbutrin alternative

Switching from Wellbutrin to another antidepressant may be necessary due to a poor response or unacceptable side effects. However, there are risks such as withdrawal symptoms if the transition isn’t managed correctly. A healthcare professional must manage any discontinuation or change in medicines.

A common switching strategy involves tapering the currently prescribed antidepressant, followed by the appropriate washout period before prescribing the new treatment. Gradual dose reduction, as recommended by a healthcare provider, reduces the chance of withdrawal complications.

Choosing the right path for depression treatment

Always consult with a healthcare provider or other mental health professional about what types of drugs and treatments are best to resolve depression. If Wellbutrin does not work, there are many other antidepressants to choose from, including antidepressants that work differently from standard antidepressants. Consult with the healthcare provider about possible side effects and any adjunctive therapies.