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

In this article:

• What can I take in place of Wellbutrin?
• Compare Wellbutrin (bupropion) alternatives
• Top 5 Wellbutrin alternatives
• Natural alternatives to Wellbutrin
• How to switch to a Wellbutrin alternative

In this article

• What can I take in place of Wellbutrin?
• Compare Wellbutrin (bupropion) alternatives
• Top 5 Wellbutrin alternatives
• Natural alternatives to Wellbutrin
• How to switch to a Wellbutrin alternative

Bupropion hydrochloride, also known by the trade name Wellbutrin, is an atypical antidepressant. It is approved by the Food and Drug Administration (FDA) for treating major depressive disorder. Wellbutrin works by increasing the levels of norepinephrine and dopamine in the brain. It differs from the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors SNRIs because they don’t affect serotonin levels. 

Bupropion immediate-release comes in a generic form as a 75 and 100 mg tablet. It is also available as Wellbutrin SR (sustained-release) in 100, 150, and 200 mg tablets and Wellbutrin XL (extended-release) in 150 and 300 mg tablets. In addition to the treatment of depression, bupropion is available under the brand name Zyban, which has been FDA approved as a smoking cessation medication.

What can I take in place of Wellbutrin?

The American Psychological Association guidelines recommend second-generation antidepressant medications, which include SSRIs, such as Prozac (fluoxetine), Paxil (paroxetine), and Zoloft (sertraline), or SNRIs, such as Cymbalta (duloxetine), Pristiq (desvenlafaxine), and Effexor (venlafaxine), as first-line treatments. However, these two subclasses of antidepressants don’t always work for everyone, and, in many cases, atypical antidepressants are prescribed. Atypical antidepressant drugs have mechanisms of action that differ from SSRIs and SNRIs. 

There are other options available to treat depression if Wellbutrin is not effective or if there are concerns about side effects or drug interactions with other medicines. These alternative prescription medications include SSRIs, SNRIs, and other less commonly prescribed classes of antidepressants, such as tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs). These options may suit certain individuals due to their different uses, side effect profiles, and dosages. The table below focuses on the most common alternatives of Wellbutrin.

Other alternatives to Wellbutrin

• Abilify (aripiprazole)
• Amitriptyline HCl
• Anafranil (clomipramine)
• Celexa (citalopram)
• Eldepryl (selegiline)
• Nardil (phenelzine)
• Norpramin (desipramine)
• Pamelor (nortriptyline)
• Parnate (tranylcypromine)
• Pristiq (desvenlafaxine)
• Protriptyline HCl
• Serzone (nefazodone)
• Surmontil (trimipramine)
• Tofranil (imipramine)

Top 5 Wellbutrin alternatives

With the likelihood that the first-line antidepressants from the SSRI and SNRI drug classes have been eliminated as alternatives due to ineffectiveness or side effect concerns, the following are some of the most common alternatives to Wellbutrin.

1. Remeron (mirtazapine) 

Remeron is in a class of medicines known as tetracyclic antidepressants. It is a serotonin antagonist that stimulates the release of norepinephrine. Remeron is available as a 15, 30, and 45 mg oral tablet and a 15, 30, and 45 mg oral disintegrating tablet. It is usually prescribed to be taken once daily at bedtime. The orally disintegrating tablets dissolve in the mouth and can be swallowed with or without liquid.

Adverse effects of Remereron include increased appetite, weight gain,  dry mouth, drowsiness, and dizziness. Serious, though uncommon, side effects include a low white blood cell count, serotonin syndrome, angle-closure glaucoma, abnormal heart rhythm, manic episodes, seizures, and low sodium levels in the blood (hyponatremia). Remeron also carries the black box warning about worsening depression and suicidal thoughts and behavior.

2. Trazodone

Trazodone, known by the brand name Desyrel, increases the neurotransmitters serotonin and noradrenaline levels in the brain. It is available as a 50, 100, 150, and 300 mg oral tablet, and an initial dose of 150 mg per day in divided doses is recommended. The dosage may be increased gradually, and if drowsiness occurs, the major portion of the daily dose may be given at bedtime.

Adverse effects associated with trazodone include drowsiness, dry mouth, headache, dizziness, and weight loss. Serious, though uncommon, side effects include orthostatic hypotension (low blood pressure when changing from a standing to a sitting or lying position), priapism (a painful erection that lasts more than 6 hours), irregular heartbeat (QT prolongation), serotonin syndrome, bleeding problems, manic episodes, vision problems, and low sodium levels in the blood (hyponatremia). Trazodone also carries a black box warning cautioning about worsening depression and suicidal thoughts and behavior.

3. Trintellix (vortioxetine)

Trintellix works as an antidepressant by enhancing the activity of the neurotransmitter serotonin in the brain by blocking serotonin reuptake. Trintellix is available as 5, 10, and 20 mg oral tablets. The recommended starting dose is 10 mg once daily, which may be increased to 20 mg daily as tolerated.

The most common adverse effects of Trintellix are GI side effects (nausea, diarrhea, constipation, vomiting, flatulence), dry mouth, dizziness, abnormal dreams, itching, and sexual dysfunction. Less common serious side effects include serotonin syndrome, bleeding problems, activation of mania or hypomania in patients with bipolar disorder, angle-closure glaucoma, and low sodium levels. Trintellix also carries the black box warning cautioning about worsening depression and suicidal thoughts and behavior.

4. Viibryd (vilazodone)

Viibryd is an antidepressant that has both selective serotonin reuptake inhibitor (SSRI) activity and serotonergic (5-HT1A) receptor partial agonist activity, which allows it to increase serotonin activity in the brain. Viibryd is available as 10, 20, and 40 mg oral tablets. The recommended initial dosage is 10 mg once daily with food for seven days, then it may be increased to 20 mg once daily and up to 40 mg once daily after a minimum of seven days between dosage increases.

The most common adverse effects of Viibryd include GI side effects (diarrhea, nausea, vomiting, stomach pain), insomnia, headache, dry mouth, dizziness, blurred vision, dry eye, sexual dysfunction, and changes in appetite. Less common serious side effects include serotonin syndrome, increased risk of bleeding, activation of mania or hypomania, abnormally low sodium levels, and angle-closure glaucoma. Viibryd also carries a black box warning cautioning about worsening depression and suicidal thoughts and behavior.

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

Although the combination of Lexapro and Wellbutrin SR is considered off-label, clinical trials show that this combination can be highly effective in controlling depression symptoms. 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. For example, the combination treatment has increased the risk of seizures. Also, Wellbutrin SR can cause blood levels of Lexapro to increase, leading to increased common side effects of that drug.

When considering combining Wellbutrin SR with Lexapro, discussing the correct dosage with one’s healthcare professional is essential. In clinical studies, Lexapro was initiated at 10 mg once daily, and Wellbutrin SR was added after seven days, starting at 150 mg once daily. The maximum dose of Lexapro was 20 mg per day, and the maximum dose of Wellbutrin SR was 400 mg per day.

Natural alternatives to Wellbutrin

Antidepressants are effective and often necessary for treating major depressive symptoms, but some people may benefit from natural remedies that have antidepressant effects. Serotonin levels may be increased by other measures such as exercise, sunlight or light therapy, and diets that include omega-3 fats and tryptophan (e.g., fish, nuts, poultry, and whole grains), which naturally increase serotonin levels. Over-the-counter dietary supplements and vitamins to consider include St. John’s wort, probiotics, vitamin D, vitamin B12, folate, vitamin B, niacin, magnesium, zinc, calcium, and iron. Besides the lifestyle and diet options, talk therapy remains a major non-smoking medicine alternative for the management of symptoms of depression. It’s important to obtain medical advice from a healthcare professional before trying any of these alternatives. 

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. Any discontinuation or change in medicines must be managed by a healthcare professional because antidepressants may cause withdrawal symptoms if discontinued too abruptly.

Common switching strategies involve 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.