Bupropion is an effective antidepressant but is not as commonly utilized as other antidepressants like the selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). This is likely because it is less well understood and there are some myths about this medication that limit its use.
Bupropion’s mechanism of action is very different than the SSRIs and SNRIs. It is available in an immediate release formulation that is typically dosed 2-3 times per day, a sustained release (SR) formulation that is dosed twice per day, and an extended release (XL) once a day formulation. Some of the potential side effects are less likely with the extended release formulations compared to the immediate release formulations. This is especially true of the seizure risk, which seems to be dose dependent. Many patients experienced seizures when the medication first came on the market in the 1980s but that was with only the immediate release formulation and a maximum recommended dose of 600mg per day. When the maximum recommended dose was reduced from 600mg per day to 450mg per day in the late 1980s, the risk of seizures dramatically decreased. The risk is also significantly less with the SR and XL formulations compared to the immediate release preparation, likely due to patients taking the immediate release doses too close together therefore raising the blood level acutely. It is important to consider the seizure risk in patients who have a seizure disorder or other risk factors for seizures (alcohol use disorder, elderly patients). It is important to note that bupropion doesn’t have the highest risk for seizures when looking at antidepressants. The tricyclic antidepressants carry a higher risk. The risk with bupropion is similar to escitalopram and citalopram.
Many providers have a concern that bupropion can cause or worsen anxiety. Bupropion is FDA indicated for major depression. It does not have FDA approval for the DSM anxiety disorders. It has not fared well in trials for panic disorder, social anxiety disorder and obsessive compulsive disorder, although in a small study on generalized anxiety disorder, it did about as well as escitalopram. Just because it is not a medication recommended to treat an anxiety disorder, it does not need to be avoided in patients presenting with “anxious depression”, i.e. patients who meet criteria for major depression disorder and have some anxiety symptoms but not necessarily meet criteria for a co-morbid anxiety disorder. About one in five patients with major depression can be described as having an anxious depression. While bupropion can cause activation (which can feel like anxiety) early in treatment, so can the SSRIs and SNRIs, especially for adolescents and young adults. This is a common side effect with all antidepressants used to treat teens and young adults. While there can be a period of activation early in treatment with bupropion, there are ways to mitigate the risk. Starting at a low dose and titrating slowly can help reduce the risk of activation for all antidepressants including bupropion. For example starting at 75mg of the immediate release preparation for one week then going to Wellbutrin XL 150mg qday the second week with the initial target dose is 150mg. If the initial target dose is 300mg titrate the immediate release preparation by 75mg every week (75mg qday x 1 week then 75mg bid x 1 week then 150mg qAM and 75mg qPM x 1 week then covert to Wellbutrin XL 300mg qAM).
Bupropion is less likely than the SSRIs and SNRIs to cause sexual side effects, weight gain, and sedation/lethargy. Bupropion can make patients feel more energized compared to other antidepressants. And while it is not a sedating medication, it can improve certain aspects of sleep quality, like normalizing REM latency and increasing the amount of restorative slow wave sleep. This makes it a more attractive option for some patients. Bupropion is known to have a lower rate of “switching” patients with bipolar disorder from a depressive episode to a manic episode compared to other antidepressants. Bupropion has been found to help with inattentive symptoms of ADHD and helpful in smoking cessation so can be useful for co-morbid clinical situations as well.
It is our hope that this primer on bupropion helps primary care providers feel more comfortable with the medication to consider using it for their patients in appropriate clinical cases. We reviewed some of the myths about this medication, which hopefully leads clinicians to have a better understanding of the nuances of using bupropion.