Serious neuropsychiatric adverse events have been reported in patients taking bupropion hydrochloride extended-release tablets (SR) for smoking cessation. These postmarketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide [see Adverse Reactions ( 6.2)] . Some patients who stopped smoking may have been experiencing symptoms of nicotine withdrawal, including depressed mood. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication. However, some of these adverse events occurred in patients taking bupropion hydrochloride extended-release tablets (SR) who continued to smoke. 

Neuropsychiatric adverse events occurred in patients without and with pre-existing psychiatric disease; some patients experienced worsening of their psychiatric illness. Observe patients for the occurrence of neuropsychiatric adverse events. Advise patients and caregivers that the patient should stop taking bupropion hydrochloride extended-release tablets (SR) and contact a healthcare provider immediately if agitation, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior. The healthcare provider should evaluate the severity of the adverse events and the extent to which the patient is benefiting from treatment, and consider options including continued treatment under closer monitoring or discontinuing treatment. In many postmarketing cases, resolution of symptoms after discontinuation of bupropion hydrochloride extended-release tablets (SR) was reported. However, the symptoms persisted in some cases; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve.

The neuropsychiatric safety of bupropion hydrochloride extended-release tablets (SR) was evaluated in a randomized, double-blind, active- and placebo-controlled study that included patients without a history of psychiatric disorder (non­psychiatric cohort, n=3,912) and patients with a history of psychiatric disorder (psychiatric cohort n=4,003). In the non-psychiatric cohort, bupropion hydrochloride extended-release tablets (SR) were not associated with an increase composite of the following neuropsychiatric (NPS) adverse events: severe events of anxiety, depression, feeling abnormal, or hostility, and moderate or severe events of agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, and irritability. In the psychiatric cohort, there were more events reported in each treatment group compared with the non-psychiatric cohort and the incidence of events in the composite endpoint was higher for bupropion hydrochloride extended-release tablets (SR) compared with placebo: Risk Difference (95% CI) vs. placebo was 2.2% (-0.5, 4.9) for bupropion hydrochloride extended-release tablets (SR).

In the non-psychiatric cohort, neuropsychiatric adverse events of a serious nature were reported in 0.5% of patients treated with bupropion hydrochloride extended-release tablets (SR) and 0.4% of placebo-treated patients. In the psychiatric cohort, neuropsychiatric events of a serious nature were reported in 0.8% of patients treated with bupropion hydrochloride extended-release tablets (SR), all involving psychiatric hospitalization. In placebo-treated patients, serious neuropsychiatric events occurred in 0.6%, with 0.2% requiring psychiatric hospitalization [see Clinical Studies ( 14)] .