Disclaimer: None of the information in this article constitutes medical advice, and is just the opinion of the writer(s) and published for informational purposes only. We recommend that patients follow their doctor’s guidance in regard to prescription medication.
Bupropion is a prescription antidepressant that’s one of the most commonly-prescribed in the U.S. Bupropion is the term for the generic version of the medication, and Wellbutrin is the branded name. These terms refer to the same active pharmaceutical ingredient, so we’ll refer to them interchangeably throughout this article.
In this article we’ll review medical studies on bupropion to determine if it’s safe and effective for treating depression. We’ll explain whether the drug can cause weight loss, highlight its side effects, and suggest some over-the-counter (OTC) that may be beneficial for patients with mild or moderate depression.
Does Bupropion Work?
As we noted in our Wellbutrin reviews article, there have been many medical studies testing the effects of bupropion for treating depression. Significant research backing is required for a drug to be approved by the Food and Drug Administration (FDA) in the U.S. to treat depression, as bupropion is.
A meta-study published in 2016 analyzed a number of clinical trials on bupropion as an antidepressant. The study authors found that the drug reduced depression on average in 24 of 27 trials. This is an impressive result in our opinion.
In trials where bupropion was compared with placebo, it was superior in 5 of the 6 trials. It’s useful for researchers to compare the efficacy of a pharmaceutical drug to placebo, which refers to inert pills with filler material.
Because the human mind can experience subjective benefit based on the expectation of benefit, placebo-controlled trials help scientists determine whether the drug is truly effective because it must be more effective than placebo to truly work, since both the active drug group and the placebo group will have the expectation of benefit.
Another medical review, published in the Primary Care Companion journal, found similarly positive results. Bupropion was effective for treating Major Depressive Disorder (MDD) in all of its dosing formats (extended release, standard release, twice-daily). The reviewers also found that the medication caused fewer side effects such as sexual dysfunction and weight gain which are common with antidepressants.
A more recent clinical trial evaluated whether bupropion is an effective adjunctive treatment (a drug used at the same time as another drug) for patients with depression who aren’t responding well to Selective Serotonin Reuptake Inhibitors (SSRI), which are the most common class of prescription antidepressants.
The researchers found that when bupropion was used as an add-on therapy in this manner, it reduced depression scores by more than the group taking SSRI alone. Researchers used a clinical grading scale for depression called the Hamilton Depression Rating Scale (HDRS). 60% of patients using bupropion and SSRI experienced a significant reduction in their depression symptoms, while only 24% of patients on SSRI alone did.
We will conclude based on the available medical research that bupropion is effective for treating depression.
How Does Bupropion Work?
Bupropion is a member of a class of drugs called norepinephrine-dopamine reuptake inhibitors (NDRI). When the drug is taken, the body’s natural processing and clearance of these important neurotransmitters is delayed, which causes artificially increased levels of them in the brain.
Dopamine directly affects mood, motivation and reward-seeking behavior, and low levels of this neurotransmitter are thought to be associated with higher risk of depression.
Norepinephrine is critically involved with proper sympathetic nervous system function, which affects the response to various stimuli. Similar to dopamine, low levels of this compound have been associated with increased risk of depression.
By artificially increasing levels of dopamine and norepinephrine, bupropion theoretically normalizes their levels in the brain and normalizes depression symptoms. However, it has not been conclusively proven that patients with depression have naturally low levels of these neurotransmitters.
Does Bupropion Cause Weight Loss?
Patients are often curious about whether bupropion causes weight loss, because there were some early clinical trials which found reduced body weight as a side effect of the drug.
One medical study published in 2002 found that the standard release (SR) form of bupropion did cause an average weight loss throughout the trial. Obese patients using bupropion lost 4.6% of their baseline weight over 12 weeks, while the placebo group lost an average of 1.8% of their baseline weight. This is a pretty significant weight loss, and equates to weight loss of 11.5 pounds (lbs) for someone who started the trial at 250 lbs.
A recent medical review of bupropion for weight loss analyzed data from three individual clinical trials on the topic, and found that the medication did cause an average weight loss across all three trials. The researchers noted that although bupropion isn’t approved by the FDA for weight loss, “There might be a role for this drug as a second-line consideration for obesity”.
Bupropion is actually one of two active ingredients in a prescription medication that’s approved by the FDA called Contrave. However, we described in our recent Contrave reviews article how this medication has a documented side effect of suicidal thoughts, so it may be better for patients to speak with their doctor about alternative weight loss medications.
Based on the available preliminary research, bupropion does appear to be effective for weight loss, but more studies are needed to conclusively say so. We don’t recommend using bupropion for weight loss alone, because it’s not approved by the FDA for that health outcome. We would consider weight loss to be a beneficial secondary outcome for overweight patients prescribed the drug for depression, but using it for weight loss alone would be an “off-label” use.
Bupropion Side Effects
Bupropion does cause side effects in some patients, as do most prescription antidepressants. A medical review documents that “many side effects occur” in over 10% of patients on the medication. Some of the most common side effects are tachycardia (rapid heart beat), headache, insomnia and constipation.
The more rare, but more concerning side effect in our opinion is the risk for suicidal thoughts and actions. Bupropion’s FDA label contains a “black box” warning indicating this side effect, which is the most severe category of warning issued by the FDA. It indicates a side effect that may be life-threatening.
According to the FDA label, bupropion may increase the risk of suicidal behavior in children, adolescents and young adults. The risk does not appear to be increased relative to placebo in patients over the age of 24.
This information suggests that young adult patients or parents caring for their child may want to speak with their doctor or pediatrician about an alternative medication for depression. There are other drugs which don’t cause an increased risk of suicide, and this risk seems like a very concerning one that may be best to avoid altogether.
OTC Antidepressants Worth Considering
There are some OTC dietary supplements with significant research backing that patients with mild-to-moderate depression may benefit from considering. We’re not suggesting these compounds are as effective as bupropion; but they may have a more favorable side effect profile.
St. John’s Wort
St. John’s Wort is one of the most well-studied herbal compounds with antidepressant effect. It’s sourced from a flowering plant native to Europe and North Africa.
This botanical compound, when taken in extract form, has been proven in medical studies to treat mild-to-moderate depression as effectively as prescription medication with no side effects. It’s not as well-studied for treating major depression, which is the clinical diagnosis that often precedes a prescription drug treatment.
The St. John’s Wort format used in most medical trials that we’ve reviewed is standardized to 2-5% hyperforin and 0.3% hypericin. These are the active chemical compounds in the plant. A botanical extract is a more potent form of the plant, as ethanol is used to create a higher percentage of the active chemical constituents.
Omega-3 Fats
Omega-3 fatty acids, which are predominantly sourced from fish, are linked to many favorable health outcomes. As we documented in our article on are fish oil supplements beneficial, one of these benefits is an antidepressant effect.
One clinical trial found that omega-3 supplementation at a dose of 6.6 grams (g) per day effectively treated major depressive disorder, which is impressive given that severe depression is often more challenging to treat with dietary supplements. Recall that St. John’s Wort is only proven effective for mild-to-moderate depression.
A more recent meta-study, published in the Translational Psychiatry journal, analyzed 26 clinical trials on omega-3 fatty acids and depression. The researchers concluded that omega-3 supplementation even at as low a dose as 1 g or less daily is an effective antidepressant.
Fish oil doesn’t need to be sourced from supplements; it can be obtained from whole fish consumption as well. It’s just harder to measure dosage with whole foods.
Bupropion and Alcohol
Bupropion may negatively interact with alcohol if the alcohol is consumed at high doses. Bupropion’s FDA label mentions that patients who consume high amounts of alcohol should speak with their doctor prior to taking the medication, and that patients consuming high amounts of alcohol that abruptly stop while using bupropion may be at higher risk for severe side effects such as seizure.
The amount of drinks categorized as “high” is not described on the label.
It seems as though bupropion has no interactions with alcohol consumed in moderate amounts, but we would strongly suggest that patients who regularly consume alcohol speak with their doctor about what constitutes a “high” amount in the context of this potential medication interaction.
Should I Take the Branded Version of Bupropion?
As referenced in the intro of this article, the branded version of bupropion is called Wellbutrin. Patients are often confused about which of the two medications they should take, because both contain the same active drug ingredient.
We would recommend that patients speak with their doctor about bupropion rather than Wellbutrin.
An extensive medical review published in 2019 compared the effectiveness of branded and generic versions of drugs, and found them to be equally effective on average. This makes logical sense, given that both categories of drugs contain the same active ingredient.
Generic drugs are often significantly cheaper than branded drugs. On CostPlusDrugs, which is Mark Cuban’s generic drug venture, the cost of 30 days worth of bupropion SR is only $5.10.
Can Bupropion Treat ADHD?
Attention Deficit Hyperactivity Disorder (ADHD) has been theorized to be related to dopamine dysfunction, so patients are often curious about whether bupropion can treat this condition given that it modulates dopamine levels.
An extensive medical review published in 2017 examined whether bupropion was an effective treatment for ADHD. The researchers analyzed a data set of six individual clinical trials, totalling 438 patients. While the drug was found to reduce symptoms of ADHD, the study authors described the evidence as “low-quality” due to methodological issues in some of the studies.
We would not recommend using bupropion for ADHD, as the drug is not approved by the FDA for this purpose and this would be an “off-label” use. There are existing medications with much more research backing for treating ADHD in adults that patients can speak to their doctor about.
Can Bupropion Treat Anxiety?
Bupropion has been studied in clinical trials for its efficacy in treating anxiety disorders.
A medical review compared data on bupropion to SSRI drugs for treating anxiety. 6% more anxious patients responded favorably to SSRI drugs than bupropion, which is to be expected given that SSRI drugs are commonly used to treat anxiety.
Bupropion is not approved by the FDA to treat anxiety and we would not recommend using it off-label for this purpose.
Does Bupropion Cause Sexual Side Effects?
Many prescription antidepressants cause sexual side effects, particularly in men, so patients often ask whether bupropion carries the risk of these side effects.
An extensive meta-study published in the Cureus journal examined the side effect profile of bupropion and contains some interesting findings on sexual side effects. Not only was bupropion found to be more favorable than SSRIs in regard to sexual side effects, the drug may actually improve sexual function.
The researchers noted that some medical research found bupropion to increase sexual desire and sexual frequency compared to placebo.
We will conclude based on the available research that bupropion is unlikely to cause sexual side effects in either sex.
Does Bupropion Cause Withdrawal Symptoms?
Withdrawal symptoms can be caused by the addictive nature of a drug, and the body’s tolerance to it. Not all prescription drugs cause withdrawal symptoms.
While there are some case reports in the medical literature (example 1, example 2) of bupropion causing withdrawal symptoms, we cannot locate a comprehensive study proving this drug causes withdrawal symptoms in a subset of patients.
A case report documents one single patient’s response to a drug, and while it can be valuable for further research, it doesn’t necessarily prove that a drug causes the documented effect on average, given that bupropion is prescribed millions of times annually.
Bupropion’s FDA label does not mention withdrawal symptoms other than in regard to concurrent nicotine use. Patients who smoke while using bupropion should speak to their doctor about this risk.
Bupropion doesn’t appear to cause withdrawal symptoms in patients who don’t smoke.
Is Bupropion an SSRI?
Patients are often curious about whether or not bupropion is an SSRI, because this class of drugs is typically prescribed for depression. Bupropion is not an SSRI, but is rather an NDRI as described in the above section outlining how the drug works.
Both of these classes of medication have similar mechanisms of action. SSRI drugs inhibit the body’s natural processing of serotonin, allowing its levels to remain artificially elevated in the brain. NDRI drugs inhibit the body’s processing of dopamine and norepinephrine, causing levels of these two neurotransmitters to remain artificially elevated in the brain.
Bupropion Dosage
Bupropion is prescribed at a wide range of doses, and in a wide variety of different formats. The drug has an Immediate Release (IR) form, and an Extended Release (XR) form.
According to StatPearls, which is one of the largest free medical databases in the U.S., the effective daily dose range for bupropion is between 75 milligrams (mg) and 522 mg. The IR pills range between 75 and 100 mg, while the XR pills range between 100 and 450 mg.
Doctors will typically prescribed bupropion at a lower starting dose of around 75 or 100 mg, and may increase the dose slowly over the course of weeks if the patient isn’t experiencing benefit. Lower doses generally confer lower risk of side effects, so if a patient has success on a lower dose it’s a good sign.
