“Wellbutrin helps your mood get well”. Bupropion (Wellbutrin), the #28 most prescribed overall medication, is a stimulating antidepressant that enhances norepinephrine and dopamine activity. Unlike most other modern antidepressants, it does not enhance serotonin activity. It is used for smoking cessation because it is stimulating like nicotine. These stimulating properties also make it useful for ADHD. Bupropion has demonstrated cognitive benefits. Clinicians tend to avoid prescribing it to individuals with anxiety disorders, but despite its stimulating properties, bupropion does not appear to exacerbate anxiety (Wiseman, 2012).
The serotonergic antidepressants cause sexual dysfunction. Bupropion is not serotonergic and actually improves sexual functioning. It is used as an add-on to SSRIs to ameliorate sexual problems (off-label).
Bupropion is contraindicated in patients with a current or prior diagnosis of bulimia or anorexia because of a higher reported incidence of seizures in such patients taking Wellbutrin.
Wellbutrin suppresses appetite and may cause modest weight loss. As with other stimulant-type medications, bupropion decreases appetite via adrenergic and dopaminergic receptors in the hypothalamus. The incidence of weight loss greater than 5 pounds is about 28%. CONTRAVE is a fixed-dose combination of bupropion with the opioid antagonist naltrexone, approved for long term treatment of obesity.
If taken by individuals with bipolar disorder, bupropion appears less likely to induce mania compared to serotonergic antidepressants.
Bupropion’s chemical structure is similar to synthetic “bath salt” drugs. Wellbutrin is not a controlled substance and is not generally considered a drug of abuse. It increases dopamine levels in the prefrontal cortex (underactive in ADHD) but not in the nucleus accumbens (reward center), at least not at standard doses. However, bupropion is avoided by many prescribers in correctional facilities because inmates have collected tabs to crush and snort as “poor man’s cocaine”.
Bupropion, an NDRI, is a much weaker inhibitor of DA and NE reuptake than the Schedule II controlled stimulants approved for ADHD like methylphenidate (Ritalin) and amphetamine (Adderall). Ritalin and Adderall are referred to as DNRIs because their dopaminergic effect is stronger than their noradrenergic effect. Solriamfetol (Sunosi), approved for excessive daytime sleepiness (due to narcolepsy or sleep apnea) is a Schedule IV NDRI.
Bupropion has anti-inflammatory properties as a tumor necrosis factor (TNF) inhibitor. For treatment-resistant depression, adding bupropion to an SSRI is effective for patients who are overweight or have high C-reactive protein (CRP), a marker of inflammation (Jha MK, 2017). Otherwise, adding bupropion to an SSRI appears to be of no benefit for treatment-resistant depressant.
Risk of overdose mortality with bupropion is higher than with most other modern antidepressants. Of 51,118 single-drug exposures to bupropion reported to Poison Control, there were 3,239 major serious outcomes and 47 deaths (Nelson & Spyker, 2017).