Treatments for smoking cessation include counseling without pharmacological intervention (“cold turkey”) and a variety of nicotine replacement products, bupropion (an antidepressant), and varenicline (a partial agonist of a4ß2 nicotinic acetylcholine
The U.S. Food and Drug Administration (FDA) has required Boxed Warnings (a.k.a. “Black Box Warnings”) for physicians, and a mandatory Medication Guide for patients regarding serious psychiatric side effects for two pharmacological treatments, varenicline and bupropion.
The warnings refer to suicidal behaviors prominently, but also mention depression while noting “Depressed mood may be a symptom of nicotine
While suicidal behaviors are not associated with smoking cessation itself, they are linked to at least 58 different approved prescription drugs that have Boxed Warnings, Warnings or Precautions in the package inserts.
The list includes varenicline, 23 antidepressant drugs including bupropion, 17 anti-epileptic drugs, and treatments for asthma, viral illness, malaria prevention and acne.
Inspection of the warnings for the various compounds reveals that suicidal events were rare in clinical trials. Class warnings for anti-epileptic and antidepressant drugs were based on FDA meta-analyses of numerous clinical trials and were extended to drugs with similar indications or mechanisms of action. Most other warnings were based on adverse event
In this study researchers examine the comparative neuropsychiatric safety profiles of varenicline, bupropion and nicotine replacement products with regard to suicidal/self-injurious behavior and depression as reflected in adverse drug event data.
These data support three conclusions about suicidal/self-injurious behavior and depression in smoking cessation treatment.
First, the risks of these reported serious events were higher among nicotine replacement patients compared to a broader population prescribed commonly used antibiotics, suggesting higher risks in the smoking cessation treatment population employing pharmacological
Second, bupropion has some additional excess reported risk when used for smoking cessation compared to the nicotine
Finally, varenicline has markedly higher reported risk than any of the comparators, a risk that was not reduced regardless of the form of adjustment used.
In addition, these findings were consistent with a simpler study using United Kingdom adverse event data and a prospective cohort study in New Zealand.
Thomas J. Moore, Curt D. Furberg, Joseph Glenmullen, John T. Maltsberger, Sonal
Suicidal Behavior and Depression in Smoking Cessation Treatments