What medications are effective for treating depression associated with nicotine withdrawal?

From the Guidelines

Bupropion SR is the most effective medication for managing depression associated with nicotine withdrawal, as it treats both depression and nicotine addiction. According to the U.S. Preventive Services Task Force recommendation statement published in the Annals of Internal Medicine in 2015 1, bupropion SR has been shown to increase smoking abstinence rates from approximately 11% in control groups to 19% in those using the medication. The typical dosage of bupropion SR is 150mg daily for 3 days, then 150mg twice daily for 7-12 weeks.

Key Considerations

• Bupropion SR is the only pharmacotherapy intervention approved by the FDA for the treatment of tobacco dependence in adults that also has antidepressant properties.
• Combining bupropion SR with behavioral support, such as counseling or therapy, may increase cessation rates and improve management of depression associated with nicotine withdrawal.
• Other medications, such as selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants, may also be used to manage depression, but bupropion SR is specifically approved for smoking cessation and has been shown to be effective in this context 1.

Treatment Approach

• Medication should be combined with counseling or behavioral therapy for optimal results.
• Regular follow-up with a healthcare provider is essential to monitor effectiveness and adjust treatment as needed.
• Side effects of bupropion SR may include nausea, sleep disturbances, or dry mouth, and should be closely monitored by a healthcare provider.

From the FDA Drug Label

Bupropion hydrochloride extended-release tablets (XL) are not approved for smoking cessation treatment; however, bupropion HCl sustained-release is approved for this use. Serious neuropsychiatric adverse events have been reported in patients taking bupropion for smoking cessation These postmarketing reports have included changes in mood (including depression and mania), psychosis, hallucinations, paranoia, delusions, homicidal ideation, aggression, hostility, agitation, anxiety, and panic, as well as suicidal ideation, suicide attempt, and completed suicide Some patients who stopped smoking may have been experiencing symptoms of nicotine withdrawal, including depressed mood. Depression, rarely including suicidal ideation, has been reported in smokers undergoing a smoking cessation attempt without medication.

Bupropion can be used to help with nicotine withdrawal related depression. However, it's essential to monitor patients for neuropsychiatric adverse events, including depression, suicidal ideation, and suicide attempt. Patients should be advised to stop taking bupropion and contact a healthcare provider immediately if they experience any of these symptoms 2.

From the Research

Medications for Nicotine Withdrawal Related Depression

• The antidepressants bupropion and nortriptyline have been shown to aid long-term smoking cessation, as evidenced by multiple studies 3, 4, 5, 6.
• Bupropion has been found to increase the odds of cessation, with a risk ratio of 1.62 in one meta-analysis 6.
• Nortriptyline has also been found to increase the odds of cessation, with a risk ratio of 2.03 in one meta-analysis 6.
• Selective serotonin reuptake inhibitors, such as fluoxetine, have not been found to aid cessation 3, 4, 6.
• Monoamine oxidase inhibitors, such as moclobemide, have also not been found to aid cessation 6.
• The atypical antidepressant venlafaxine has not been found to aid cessation in one trial 6.
• The herbal therapy St John's wort and the dietary supplement SAMe have not been found to aid cessation in two trials and one trial, respectively 6.

Effectiveness in Smokers with Current or Past Depression

• Adding a psychosocial mood management component to a standard smoking cessation intervention has been found to increase long-term cessation rates in smokers with both current and past depression 7.
• Bupropion may increase long-term cessation in smokers with past depression, with a risk ratio of 2.04 in one meta-analysis 7.
• There is limited evidence for the use of bupropion in smokers with current depression 7.
• There is not enough evidence to evaluate the effectiveness of other antidepressants, such as fluoxetine and nortriptyline, in smokers with current or past depression 7.

Safety and Adverse Events

• Bupropion has been associated with a risk of seizures, with an estimated risk of about 1 in 1000 3, 4, 6.
• Bupropion has also been associated with suicide risk, but whether this is causal is unclear 6.
• Nortriptyline has the potential for serious side-effects, but none have been seen in the few small trials for smoking cessation 6.