Table 5. Varenicline continued...
There are concerns that varenicline and bupropion HCl may be associated with an increased risk of depression and other neuropsychiatric events, including suicidal behaviors.[15,19] This concern is based on postmarketing reports and post hoc analyses.[15,19] Attempted and completed suicides have also been reported in patients taking these medications. These neuropsychiatric events have been reported in patients with or without preexisting psychiatric illness.
In July 2009, the FDA required the manufacturers of both varenicline and bupropion HCl to add a boxed warning to the product labeling, based on the continued review of postmarketing adverse event reports. The warning describes the risk of the following neuropsychiatric events from postmarketing reports:[15,20]
- Changes in mood (including depression and mania).
- Homicidal ideation.
- Suicidal ideation, suicide attempts, and completed suicides.
The warning acknowledges that nicotine withdrawal related to smoking cessation may contribute to these neuropsychiatric events. The warning also acknowledges that causality between the medication exposure and these events cannot be conclusively established and states that the risks of these medications should be weighed against the potential health benefits of quitting smoking.
It is recommended that clinicians closely monitor all patients taking varenicline and bupropion HCl. The premarketing smoking cessation studies of these medications excluded patients with serious psychiatric illness (e.g., schizophrenia, bipolar disorder, and major depressive disorder), suggesting that the safety of these medications for these patients has not been investigated.[15,20] Therefore, during smoking cessation, it is important to especially monitor patients with preexisting psychiatric illness who are receiving varenicline and bupropion HCl for smoking cessation.
Patients can be carefully matched to specific smoking cessation strategies. Some smokers can quit with the help of counseling or psychological interventions, while others might need nicotine replacement therapies. Some smokers might need medications to successfully quit smoking. Given the significant health benefits derived from smoking cessation, medications can be used in these patients with careful monitoring.
Table 6. Bupropion HCl
|HCl = hydrochloride; Rx = prescription.|
|Rx||Zyban||150 mg/d × 3 days, then increase to 300 mg/d × 7–12 weeks||Insomnia, dry mouth, dizziness, rhinitis||Do not take with Wellbutrin or Wellbutrin SR.|
|Higher incidence of seizures in patients treated for bulimia or anorexia.|
|Do not prescribe >300 mg/d for patients being treated for bulimia.|
Although bupropion HCl (Zyban) is the only FDA-approved antidepressant for smoking cessation, fluoxetine HCl (Prozac) has been studied and shown to be effective.[Level of evidence: I] However, fluoxetine HCl also carries a boxed warning describing an increased risk of suicidality in adults younger than 25 years. (Refer to the Depression and Suicide section in the PDQ summary on Pediatric Supportive Care for more information.)