What is the suicide risk associated with the anti-smoking drug Chantix?
In November 2007, a year and three months after varenicline became available to the American public, the FDA announced it had received reports that patients using it for smoking cessation had experienced several serious psychological symptoms, including suicidal ideation and occasional suicidal and agitated behavior. On February 1, 2008, the FDA issued an alert, noting that "it appears increasingly likely that there is an association between varenicline and serious neuropsychiatric symptoms."
As of February 2008, 491 cases of suicidal thinking or behavior were reported, including 420 in the United States. Thirty-nine of the 491 cases resulted in suicide, including 34 in the United States. More than 6 million people have been prescribed the pill since it was launched. When considering the number of prescriptions, the risks of serious psychological symptoms are extremely low, and the risk that those symptoms will result in death is even lower. When weighing such risks against the risks of continued smoking, varenicline actually ends up being safer than continued tobacco use.
When considering the number of prescriptions, the risks of serious psychological symptoms are extremely low, and the risk that those symptoms will result in death is even lower.
Sorting out the cases individually in order to determine what role, if any, varenicline has in contributing to or even causing these symptoms remains a daunting task. One of the more celebrated cases, the case of Carter Albrecht who was shot by his neighbor after striking his girlfriend and entering his neighbor's house, was probably due to mixing the drug with large amounts of alcohol. Suicidal thinking is a complex behavior with multiple contributing factors, including personality, mood, environment, history, and other substance or prescription medication use. But the end result is often extremely tragic and traumatic, prompting public outcry and a large amount of press. It is important to keep these issues in mind when considering the risks of using this medication against the risks of continuing to smoke.
What other non-NRTmedication therapies are available, if any?
A number of other medications have been studied, but only two are currently recommended as second-line therapies, should individuals either fail the first-line therapies or experience side effects that contraindicate future use. It is important to remember when selecting medications that prior failure with a medication does not predict future failure. Thus, second-line therapies are generally used when first-line therapies are contraindicated or some other compelling clinical reason suggests their trial over a first-line therapy. An example would be for those who have migraines in addition to tobacco dependence, where the clinician would suggest trying nortriptyline as a first-line therapy because it is commonly used to treat migraine headaches. Additionally, there is some evidence demonstrating that women tend to have poor response rates to NRTs and therefore non-NRT medications should be considered, such as bupropion, varenicline, nortriptyline, and clonidine.
The other medications that have been extensively studied, which have not been found to be successful include selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, paroxetine, citalopram, etc., and naltrexone (ReVia). Tobacco dependence is a common problem with depression, and treating the depression can assist the patient in following through with a smoking cessation program. While SSRIs can be used in conjunction with the other smoking cessation medications to treat depression, their use as standalone agents is not effective. Naltrexone has been found to be effective in treating alcoholism in order to assist in abstinence and decrease craving. Naltrexone acts by blocking opiate receptors, but it is not helpful in decreasing craving for cigarettes. Other medications that have not been found to be helpful include benzodiazepines, beta-blockers, silver acetate, and mecamylamine. Mecamylamine is a nicotine antagonist that may prove useful in boosting the effectiveness of antidepressants, but it is too early to tell if this medication will actually pan out.
Two medications that have proven to be effective as second-line therapies include the tricyclic antidepressant, nortriptyline (trade name, Pamelor), and the antihypertensive, clonidine. Nortriptyline blocks the transporter pump and prevents the reuptake of norepinephrine, thus increasing levels of this neurotransmitter in the brain. Norepinephrine release (previously described in Question 9) is stimulated by nicotine, so that nortriptyline may aid as an indirect replacement therapy through this action. Clonidine is a more complicated medication. It generally reduces what is called sympathetic tone—that is, it reduces the "fight or flight response" by reducing the release of norepinephrine. Clonidine is used not only to reduce blood pressure, but also to treat neuropsychiatric conditions such as Tourette's disorder and ADHD (attention deficit hyperactivity disorder, discussed further in Question 83). It is also used to reduce the effects of opiate withdrawal in opiate-dependent patients. Clonidine, in a sense, does the exact opposite of nortriptyline, demonstrating the underlying complexity of nicotine addiction and how oversimplified our current theories are about this drug and its effects on the brain and body.