Vancouver—How safe are pharmacotherapies for smoking cessation? A new study points out the medications are widely prescribed, even though worries persist about increased risk of cardiovascular (CV) and neuropsychiatric adverse effects.

A study published in the journal Addiction  assessed the relative CV and neuropsychiatric safety of varenicline and bupropion compared with nicotine replacement therapies (NRT) in adults without a recent history of depression.

To do that, Canadian researchers from the University of British Columbia used U.S. administrative data from 2006 to 2016 from an insurance database covering claims for more than 100 million individuals.

The 618,497 participants, who were from three study cohorts of new users, were adults who had no diagnosis or treatment for depression in the prior 12 months.

Compared with the 32,237 users of nicotine replacement therapy, varenicline—used by 454,698 study participants—was found to be associated with a 20% lower 1-year CV risk (adjusted relative risk [RR] = 0.80; 95% CI, 0.75-0.85). Bupropion, which was prescribed to 131,562 patients, was associated with a 25% lower 1-year CV risk (RR = 0.75; 95% CI, 0.69-0.81).

At the same time, varenicline was associated with a 35% lower 1-year risk of neuropsychiatric hospitalization versus NRT (RR = 0.65; 95% CI, 0.59-0.72), and bupropion was associated with a 21% increase in 1-year risk of neuropsychiatric hospitalization (RR = 1.21; 95% CI,1.09-1.35).

“Varenicline compared with nicotine replacement therapy does not appear to be associated with an increased risk of cardiovascular or neuropsychiatric hospitalizations,” the authors conclude. “Bupropion appears to be associated with a lower risk of cardiovascular hospitalization and a higher risk of neuropsychiatric hospitalization, compared with nicotine replacement therapy.”

In 2009, the FDA’s Adverse Event Reporting System imposed a black box warning on varenicline for psychiatric side effects and included additional warnings in the prescribing information concerning CV events in 2012 and serious neuropsychiatric symptoms and suicidality in 2013. The black box warning was removed in 2016.

Bupropion was subject to the same FDA black box warning as varenicline in 2009, with warnings added regarding hypertension and seizure risk, according to the report.

“While we support the FDA’s efforts to monitor the safety of its approved products, the warnings for varenicline and bupropion have become increasingly inconsistent with evidence from subsequent clinical trials and observational research,” said lead author Greg Carney, PhD. “We hope that our study’s findings will promote a better understanding of these medications for quitting smoking.”

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