Bupropion - Adverse Effects - Psychiatric

Psychiatric

The FDA requires all antidepressants, including bupropion, to carry a black box warning stating that antidepressants may increase the risk of suicide in persons younger than 25. This warning is based on a statistical analysis conducted by the FDA which found a 2-fold increase of the suicidal ideation and behavior in children and adolescents, and 1.5-fold increase of suicidality in the 18–24 age group.

Suicidal ideation and behavior in clinical trials are rare. For the above analysis, the FDA combined the results of 295 trials of 11 antidepressants for psychiatric indications in order to obtain statistically significant results. Considered separately, bupropion and nine other antidepressants were not statistically different from placebo. Only fluoxetine caused a significant decrease in suicidal ideation.

Suicidal behavior is less likely when bupropion is prescribed for smoking cessation. According to a 2007 Cochrane Database review, there have been four suicides per one million prescriptions and one case of suicidal ideation per ten thousand prescriptions of bupropion for smoking cessation in the UK. The review concludes, "Although some suicides and deaths while taking bupropion have been reported, thus far there is insufficient evidence to suggest they were caused by bupropion."

Two years later, the FDA issued a health advisory, which warned that the prescription of bupropion and varenicline for smoking cessation has been associated with reports about unusual behaviour changes, agitation and hostility. Some patients have become depressed or have had their depression worsen, have had thoughts about suicide or dying, or have attempted suicide. This advisory was based on the postmarket review of anti-smoking products, which identified 153 reports of the suicidal adverse events for varenicline over the first year it was marketed and 75 reports for bupropion over ten years. No clear association with suicidality was identified for nicotine patch products.

Mania is one of the rare side effects of bupropion. The prescribing information notes that "it is generally believed (though not established in controlled trials)" that, should an episode of depression actually be the first presentation of bipolar disorder, treating it with antidepressants, including bupropion, may precipitate a manic episode. More recent data indicate that the addition of newer antidepressants, including bupropion, to a mood stabilizer does not cause the switch to mania more often than the addition of placebo. Moreover, when added to a mood stabilizer, bupropion and sertraline had a twice lower switch risk than venlafaxine.

Like many of the antidepressants, bupropion is associated with the potential risk for causing anxiety as a side effect. How common or severe this anxiety is remains to be fully discovered. Some studies show that it has similar anxiety side effects to the SSRI antidepressants, while others show an elevated risk for akathisia, or extreme anxiety, as high as 13.9%, or three times that from sertraline.

Psychotic symptoms associated with bupropion are rare. They may include delusions, hallucinations, paranoia, and confusion. Often, these symptoms can be reduced or eliminated by decreasing the dose or ceasing treatment. In many of these case reports, psychotic symptoms are associated with such risk factors as old age, the history of bipolar disorder or psychosis, and concomitant medications, for example, lithium or benzodiazepines. Most researchers have attributed the psychosis to bupropion's dopaminergic action.

According to several case reports, stopping bupropion abruptly may result in discontinuation syndrome expressed as dystonia, irritability, anxiety, mania, headache, aches and pains. The prescribing information recommends dose tapering after bupropion has been used for seasonal affective disorder; however it states that dose tapering is not required when discontinuing treatment for smoking cessation.