Can varenicline (Chantix) be retried in a patient who previously developed severe depression while taking it?

From the Guidelines

Varenicline should not be retried in a patient who previously developed severe depression while taking it, due to the significant risk of recurrence and potential for serious neuropsychiatric side effects. According to the 2016 NCCN clinical practice guidelines in oncology 1, varenicline has been associated with an increased risk of neuropsychiatric events, including depression and suicidal ideation. Although a 2015 systematic review and meta-analysis found no evidence to suggest that varenicline increases the risk of suicide or suicide attempts, suicidal ideation, depression, or death 1, the guidelines still recommend caution when using varenicline in patients with a history of depression.

Alternative Options

If smoking cessation medication is needed, alternative options like:

• Nicotine replacement therapy
• Bupropion should be considered instead. The FDA has issued warnings about serious neuropsychiatric side effects with varenicline, including depression, suicidal ideation, and suicidal behavior 1.

Mechanism and Monitoring

The mechanism involves varenicline's action on nicotinic acetylcholine receptors in the brain, which can affect dopamine and other neurotransmitters involved in mood regulation. If a healthcare provider does consider retreatment with varenicline in exceptional circumstances, it should only be done with:

• Extremely close monitoring
• A clear safety plan
• Involvement of mental health professionals
• After a thorough discussion of risks and benefits with the patient. The patient should be monitored frequently for any signs of:
• Depression
• Mood changes
• Suicidal thoughts, especially during the first few weeks of treatment 1.

Key Considerations

Key considerations for the use of varenicline include:

• Contraindication in patients with brain metastases due to seizure risk
• Monitoring for the development or worsening of serious neuropsychiatric issues
• Weighing the substantial benefits of immediate smoking cessation versus risks of increased hostility, depression, or suicidal behavior 1.

From the FDA Drug Label

Patients who are motivated to quit, and who did not succeed in stopping smoking during prior varenicline tablets therapy for reasons other than intolerability due to adverse events or who relapsed after treatment, should be encouraged to make another attempt with varenicline tablets once factors contributing to the failed attempt have been identified and addressed

The patient who previously developed severe depression while taking varenicline should not be retried on the medication, as the label specifies that it can be retried in patients who did not succeed due to reasons other than intolerability due to adverse events. Severe depression is considered an adverse event, and therefore, retrying varenicline in this patient is not recommended 2.

From the Research

Varenicline Retrial in Patients with Severe Depression

• The decision to retry varenicline in a patient who previously developed severe depression while taking it should be made with caution, as the medication has been associated with an increased risk of neuropsychiatric adverse events, including depression and suicidal behavior 3, 4, 5.
• Studies have shown that varenicline can exacerbate psychotic symptoms in patients with severe mental illness, and the risk of neuropsychiatric adverse events is higher in patients with a history of psychiatric illness 3, 4.
• However, some studies suggest that varenicline can be effective and well-tolerated for smoking cessation in patients with serious mental illness, including bipolar disorder and major depressive disorder, when used in combination with behavioral support and close monitoring 6.
• A case report of a patient with a history of alcohol abuse and major depression who developed neuropsychiatric symptoms after initiation of varenicline highlights the importance of careful assessment and monitoring of patients with a history of psychiatric illness who are prescribed varenicline 7.
• The Naranjo adverse drug reaction probability scale can be used to assess the likelihood of a causal relationship between varenicline and neuropsychiatric adverse events, and a score of 6 or higher indicates a probable relationship 3, 7.

Considerations for Varenicline Retrial

• Patients who have previously developed severe depression while taking varenicline should be closely monitored for signs of depression and suicidal behavior if the medication is retried 5.
• The benefits and risks of retrying varenicline should be carefully weighed, and alternative smoking cessation treatments should be considered if the patient has a history of severe mental illness or neuropsychiatric adverse events 4, 6.
• Behavioral support and close monitoring are essential for patients with serious mental illness who are prescribed varenicline, and the medication should only be used under the guidance of a healthcare professional 6.