Introduction to Bupropion Side Effects
The Covid-19 pandemic seems far behind us; however, we still face its consequences. Depression is one of them. In January 2023, around 22% of surveyed adults in the U.S. reported a depressive symptom (1), similar to 21.4% of depressive symptom reports in December 2021. (2) About 2 out of 3 patients receive medication treatment; bupropion is one of them. (3)
Bupropion, since 1989, has been available for treating major depressive disorder (MDD) (4, 5). But what about the safety profile? Does bupropion have the same side effects as other drugs for treating depression?
Unlike selective serotonin reuptake inhibitors (SSRIs), well-known antidepressants, bupropion has a different mechanism of action. It inhibits the enzymes engaged in the uptake of certain neurotransmitters. Therefore, the possible side effects vary. While you are not at risk of experiencing serotonin syndrome if you take bupropion, suicidal thoughts, and behavior are common serious side effects for both groups of medications.
Keep reading to learn about possible side effects that are associated with bupropion. It is essential to understand the situation when you or your family, or caregivers ask for medical help.
How Does Bupropion Work?
Bupropion is approved for treating a major depressive disorder (MDD) (4, 5) and smoking cessation treatment (6).
This medication belongs to the group of norepinephrine/dopamine-reuptake inhibitors (NDRI). Bupropion inhibits the enzymes responsible for the uptake of norepinephrine and dopamine from the synaptic cleft (space between two neurons where the neurotransmitter passes on the impulse). Norepinephrine (noradrenaline) and dopamine are neurotransmitters (body chemicals that carry messages from a nerve cell to other cells) that help to make you feel good and happy). This enzyme inhibition allows norepinephrine and dopamine to act longer within the neuronal synapse, and so do their effects. (7-10)
Such dual and selective reuptake inhibition makes bupropion an antidepressant with a different clinical profile comparable to other antidepressants.
Common Bupropion Side Effects
Like any other medication, bupropion has possible side effects that patients may have. If you start using bupropion, you may experience some of the most common side effects, such as dry mouth, agitation, insomnia, headache or migraine, tremor, nausea or vomiting, and constipation. In most cases, side effects are acceptable and manageable due to the benefit of bupropion that weighs over the safety profile. (4, 5)
For example, you can relieve your dry mouth if you chew gum, drink water, reduce coffee intake, or breathe through the nose. (11) Painkillers chosen by a doctor’s recommendation can help your headache, or using bupropion extended-release (XL) in the morning, once daily, may improve sleep disturbance.
Bupropion has no serotonergic activity. Therefore, unlike SSRIs, bupropion is not associated with common antidepressant-associated side effects, such as sexual dysfunction, weight gain, and sedation. (7, 12)
Yet, approximately 10% of the clinical patients stopped using bupropion due to the troublesome side effects. Agitation or mental status changes, nausea or vomiting, seizures, headaches, sleep disturbance, and rashes were the main reason for quitting bupropion therapy. (4, 5)
You can find the whole list of possible side effects in the Medication guide. Some described side effects can be mild and disappear after a few days. Call your doctor if you experience an adverse event that does not go away. (4, 5)
You can also report adverse events to your doctor or send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
In this section, you can learn about serious side effects and the cases when you need to call a doctor immediately and stop taking the therapy.
Clinical Worsening and Suicide Risk
Bupropion is used for the treatment of depression, yet, there are reported cases of its worsening. As with other antidepressants, it may also increase the risk of suicidal thinking and behavior in children and young adults. (3-4)
Short-term clinical studies where children and adolescents were using different antidepressants showed a twice higher risk of suicidal behavior or thinking than the placebo group. Although the incidence in the treatment group was only 4%, this finding was sufficient for warning patients who are using antidepressants. This risk is even higher in those with a history of suicidal behavior or young adults. (4, 5, 13)
There were no suicide cases in these short-term trials among children and adolescents. There is no evidence that this risk exists in treatment longer than several months.
The doctor will closely follow how you react to the treatment during the first weeks. Your family and caregivers can also monitor your behavior and thoughts. Call a doctor if you or they recognize anxiety, panic attacks, insomnia, irritability, aggressiveness, impulsivity, mania, and some others. (4, 5, 13, 14)
Seizures are a rare side effect of bupropion that may occur in 4 out of 1,000 patients when using up to 450 mg daily. The risk is strongly associated with the daily dose; in the range of 450 to 600 mg daily, this risk increases ten folds. A sudden dose increase and with high strength brings a higher risk. (4, 5)
Seizures may occur at the beginning of the treatment, within 6 hours after drug exposure, and several weeks after treatment initiation. In case of seizures, your doctor will discontinue bupropion and will prescribe you another medication for the treatment of depression. (4, 5, 11)
Head trauma, brain tumor, severe hepatic cirrhosis, excessive use of alcohol and sedatives, drug addiction, oral hypoglycemic, insulin, and antipsychotics are some of the risk factors for seizures in the concomitant use of bupropion. (4, 5, 11)
Because of this, you should take this medication in a dose precisely as the doctor prescribed.
Manic episodes in patients at risk of Bipolar Disorder
Bupropion is not approved for use in bipolar disorder. However, a major depressive episode may be an initial form of undiagnosed bipolar disorder. If this episode is treated with antidepressants, it may increase the risk of manic or mixed episodes or latent psychosis if the patient is at risk of bipolar disorder. (4, 5)
Due to this risk, the doctor will check if the patient has a history of bipolar disorder in the family and is at risk.
Precautions when using bupropion
Agitation and insomnia – agitation, anxiety, increased restlessness, and insomnia are symptoms that may occur shortly after the initiation of treatment. Yet, approximately 2% of patients reported severe symptoms that required treatment discontinuation with bupropion. (4, 5)
Psychosis, confusion, and other neuropsychiatric phenomena – delusions, paranoia, hallucinations, concentration disturbance, psychosis, and confusion may occur but with unknown incidence. (4, 5)
Altered appetite and weight – 28% of the patients treated with bupropion may lose weight greater than 5 lbs, the opposite of patients treated with tricyclic antidepressants or placebo that gained weight in a placebo-controlled trial. (4, 5)
Allergic Reactions – pruritus, angioedema, urticaria, and dyspnea have been reported in clinical trials and required medical treatment. Moreover, rare spontaneous postmarketing reports of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock associated with bupropion were reported. (4, 5)
Hypertension – may occur when using bupropion. (4, 5)
Wellbutrin: Recommended dose and risk of overdose
Bupropion is available as immediate-release tablets of 75 and 100 mg strength. The usual dosage is 300 mg daily, divided into three doses. The treatment begins with 100 mg twice daily, and at least after three days, your doctor may increase the dose to 100 mg three times daily. (4)
It takes about four weeks of treatment to get the maximal effect. Your doctor may increase the daily dose to 450 mg/day if needed. You’ll need to take the medication four times a day with at least four hours between doses. (4)
Your doctor may prescribe long-acting bupropion as sustained-release tablets (Wellbutrin SR or other brand names of 100, 150, or 200 mg strength) or extended-release tablets (Wellbutrin XL 150 or 300 mg, Aplenzin® of 174, 348, and 522 mg, Forfivo XL 450 mg or other brand names) mainly to reduce the risk of seizure occurrence. In both cases, the initial dose would be 150 mg once daily, taken in the morning. Then, after your doctor is convinced that you can tolerate it, the dose can be increased:
- After four days, to 300 mg of bupropion SR twice daily, or
- After a week, to 300mg of bupropion XL once daily in the morning. (4, 5)
If you take bupropion SR, take your second dose at least eight hours after the morning one.
The maximal dose of bupropion SR is 400 mg, with 200 mg as a single dose, and 300mg of bupropion XL.
Medical treatment of depression takes a long period, months, or even more. Be patient and follow the doctor’s recommendations for maintenance treatment, either with bupropion immediate, sustained, or extended-release tablets. The treatment goal is to keep remission with the lowest bupropion dose.
Overdose of 30 g or more bupropion was reported by about one-third of patients who experienced seizures. Overdose can cause other serious reactions such as hallucinations, loss of consciousness, tachycardia, arrhythmias, fever, muscle rigidity, hypotension, coma, respiratory failure, and many more. (4, 5)
Most of the patients recover after the medically managed overdose. However, bupropion overdose is associated with death. Call an emergency immediately if you or someone else notice multiple uncontrolled seizures, bradycardia, cardiac failure, and cardiac arrest signs that can appear before death. (4, 5)
The bottom line
Bupropion has been a well-known and effective antidepressant since 1989. It helps adults in the treatment of their depression.
Nausea, vomiting, agitation, seizures, or sleep disturbance are common side effects and, if not treatable, can be a cause to change the therapy. Rarely, bupropion can cause suicidal thoughts or behavior that need medical care. Call your doctor and report adverse events to FDA online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
Read the Medication Guide and talk with your doctor about the possible side effects that concern you.
Depression treatment requires long-time effort and other lifestyle changes. A healthy diet with lots of fruit and vegetables and regular physical activity will boost your serotonin level, improve mental health and support overall depression improvement. (15, 16)
Take care of yourself and be persistent in making yourself feel better again.
- Statista, Percentage of respondents in the U.S. who reported symptoms of depressive disorder in the last seven days or two weeks from April 2020 to January 2023*, 2023 Feb, https://www.statista.com/statistics/1132438/depressive-symptoms-us-adults-in-last-week/
- National Institute of Mental health, Major Depression, 2022 Jan, https://www.nimh.nih.gov/health/statistics/major-depression
- National Institute of Mental health, Major Depression, 2022 Jan, https://www.nimh.nih.gov/health/statistics/major-depression
- Food and Drug Administration, WELLBUTRIN® (bupropion hydrochloride) tablets Prescribing information, WELLBUTRIN SR® (bupropion hydrochloride) Sustained-Release Tablets prescribing information, 2006 https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018644s33s34,020358s37s40,021515s14lbl.pdf
- Food and Drug Administration, WELLBUTRIN XL® (bupropion hydrochloride extended-release tablets), Prescribing information, 2009, https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021515s023s024lbl.pdf
- Food and Drug Administration, ZYBAN® (bupropion hydrochloride) sustained-release tablets, Prescribing information, 2011, https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020711s026lbl.pdf
- S.M. Stahl, J.F. Pradko, B.R. Haight, et al., A Review of the Neuropharmacology of Bupropion, a Dual Norepinephrine and Dopamine Reuptake Inhibitor, Prim Care Companion J Clin Psychiatry. 2004;6(4):159-166. https://pubmed.ncbi.nlm.nih.gov/15361919/
- Britannica, Neurotransmitter, 2023 Feb, https://www.britannica.com/science/neurotransmitter#ref784691
- Endocrine Society, Adrenal Hormones, 2022 Jan, https://www.endocrine.org/patient-engagement/endocrine-library/hormones-and-endocrine-function/adrenal-hormones#:~:text=What%20Does%20Norepinephrine%20Do%3F,more%20energy%20to%20the%20body.
- Harvard Health Publishing, Dopamine: The pathway to pleasure, 2021 Jul, https://www.health.harvard.edu/mind-and-mood/dopamine-the-pathway-to-pleasure
- Mayo Clinic, Dry mouth treatment: Tips for controlling dry mouth, 2017 Feb https://www.mayoclinic.org/diseases-conditions/dry-mouth/expert-answers/dry-mouth/faq-20058424
- National Library of Medicine, Bupropion, 2022 Oct, https://www.ncbi.nlm.nih.gov/books/NBK470212/
- MedlinePlus, Bupropion, 2018 Feb, https://medlineplus.gov/druginfo/meds/a695033.html
- National Alliance on Mental Illnesses, Bupropion (Wellbutrin), 2023 Jan, https://www.nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Bupropion-(Wellbutrin)#:~:text=Bupropion%20hydrochloride%20is%20available%20in,4%2D6%20hours%20between%20doses.
- Głąbska D, Guzek D, Groele B, Gutkowska K. Fruit and Vegetable Intake and Mental Health in Adults: A Systematic Review. Nutrients. 2020 Jan 1;12(1):115. doi: 10.3390/nu12010115. PMID: 31906271; PMCID: PMC7019743. https://pubmed.ncbi.nlm.nih.gov/31906271/
- Serotonin: The natural mood booster, Harvard Medical School, July 20, 2021, https://www.health.harvard.edu/mind-and-mood/serotonin-the-natural-mood-booster