What is the recommended treatment for a patient with depression and a desire to quit smoking, specifically a combination of medications for smoking cessation and depression management?

From the Guidelines

For patients with depression who want to quit smoking, bupropion is the recommended first-line treatment, as it addresses both conditions simultaneously by affecting dopamine and norepinephrine levels, with a dose of 150 mg daily for 3 days, then 150 mg twice daily for 7-12 weeks for smoking cessation, which also treats depression at doses of 300-450 mg daily 1. This approach is supported by evidence suggesting that bupropion may be particularly beneficial as a smoking cessation agent for persons with depression, with similar efficacy to nicotine patch but less than that for varenicline 1. Some key points to consider when using bupropion for smoking cessation in patients with depression include:

• Bupropion reduces the seizure threshold, and should be avoided in patients with brain metastases who have a history or elevated risk of seizure 1
• Neuropsychiatric effects have been identified as a safety concern with bupropion, although recent systematic reviews of the data have found that serious neuropsychiatric adverse events were rarely associated with bupropion prescribed for smoking cessation, including studies of bupropion in patients with mental illness 1
• Recent meta-analyses do not show elevated risk of serious adverse cardiovascular effects as a result of bupropion use for smoking cessation 1 It is essential to continue treatment for at least 3 months for smoking cessation, while depression treatment typically requires 6-12 months or longer, with regular monitoring for side effects and effectiveness, as well as behavioral therapy to support both conditions 1.

From the FDA Drug Label

Bupropion hydrochloride extended-release tablets (XL) are a prescription medicine used to treat adults with a certain type of depression called major depressive disorder and for the prevention of autumn-winter seasonal depression (seasonal affective disorder). Varenicline is a nicotinic receptor partial agonist indicated for use as an aid to smoking cessation treatment.

The recommended treatment for a patient with depression and a desire to quit smoking is a combination of bupropion for depression management and varenicline for smoking cessation.

• Bupropion is used to treat major depressive disorder and can also be used as an aid to smoking cessation.
• Varenicline is used as an aid to smoking cessation treatment. It is essential to note that both medications have potential side effects and interactions, and patients should be closely monitored by their healthcare provider. Key considerations include:
• Seizure risk: Both bupropion and varenicline can increase the risk of seizures, especially in patients with a history of seizure disorders.
• Neuropsychiatric adverse events: Varenicline can cause changes in mood, psychosis, and suicidal ideation, and patients should be instructed to discontinue the medication and contact a healthcare provider if they experience such adverse events.
• Interaction with alcohol: Varenicline can increase the effects of alcohol, and patients should be instructed to reduce their alcohol consumption. Patients should be provided with appropriate educational materials and counseling to support their quit attempt and depression management. 2 3

From the Research

Treatment Options for Depression and Smoking Cessation

• The combination of varenicline and bupropion SR for smoking cessation can increase smoking abstinence rates, but it may also be associated with increased depressive symptoms, particularly in the first two weeks of treatment 4.
• Bupropion SR has been shown to be effective for smoking cessation in patients with a history of depressive disorders who are being maintained on treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants, with minimal weight gain and no evidence of emergent depression 5.
• Bupropion has been found to decrease depressive symptoms in highly nicotine-dependent smokers during active treatment, but may also lead to a rebound in depressive symptoms when discontinued 6.

Efficacy of Bupropion for Smoking Cessation and Depression

• Bupropion is superior to placebo and non-inferior to SSRIs such as escitalopram in treating major depressive disorder, and has been found to be an effective anti-smoking drug with synergistic benefits when used as a combination therapy 7.
• There is high-certainty evidence that bupropion increases smoking cessation rates when compared to placebo or no pharmacological treatment, and moderate-certainty evidence that a combination of bupropion and varenicline may result in superior quit rates to varenicline alone 8.

Safety and Tolerability of Bupropion

• Bupropion may increase serious adverse events (SAEs) and trial dropouts due to adverse events (AEs) compared to placebo or no pharmacological treatment, although the evidence is imprecise 8.
• There is high-certainty evidence that bupropion results in more trial dropouts due to AEs than placebo or no pharmacological treatment 8.

Comparison with Other Treatments

• Bupropion has been found to be less effective than varenicline and combination nicotine replacement therapy (NRT) for smoking cessation, but may be as successful as single-form NRT 8.
• Nortriptyline has also been found to aid smoking cessation when compared with placebo, although bupropion may be more effective 8.