Smoking and depression: Can smoking cessation drugs break the vicious cycle?

Smoking is the leading cause of many chronic diseases and premature death. For patients with depression, smoking may not only aggravate depressive symptoms, but also increase the risk of other diseases, forming a vicious cycle. This article will explore the safety and effectiveness of the most commonly used smoking cessation drugs (varenicline, bupropion, nicotine patch and placebo) in people who are suffering from or have suffered from major depressive disorder (MDD) based on a secondary analysis of a recent double-blind randomized controlled trial in the American Journal of Psychiatry.

In order to have a deeper understanding of the content of the trial, a brief description of the relevant drugs is given below.

Varenicline is a new type of non-nicotine smoking cessation prescription drug, which was approved by the U.S. Food and Drug Administration for adult smoking cessation in 2006, and the evidence level recommended for smokers is A. It reduces cravings and withdrawal symptoms when quitting smoking by simulating the effects of nicotine on the brain, while blocking the pleasurable effects of nicotine on the brain, thereby reducing the pleasure of smoking.
Bupropion was originally used as an antidepressant, but it was later found to help quit smoking as well. Bupropion works by increasing levels of norepinephrine and dopamine in the brain, chemicals involved in mood regulation and pleasure. Bupropion is usually started 1 to 2 weeks before starting to quit smoking, at a dose of 150 mg twice a day. It can cause adverse effects such as headache and nausea, and is not suitable for people with a history of epilepsy or certain other health conditions.

The nicotine patch is an over-the-counter nicotine replacement therapy used to help smokers reduce withdrawal symptoms when they quit smoking. The patch slowly releases nicotine through the skin, simulating the nicotine intake when smoking, thereby reducing dependence on tobacco. Users usually start with a higher dose and gradually reduce the dose until they stop using it completely. Nicotine patches can be worn all day and are usually changed once a day and are attached to clean, hairless skin such as the upper arm, chest, back, or outer thigh. There may be mild adverse reactions to the use of nicotine patches, such as skin irritation or sleep disturbances, but they are generally safe.

A placebo is a substance or treatment used in medical research and clinical treatment that has no specific active ingredient and therefore has no effect on treating a specific disease. Placebos can be in the form of pills, capsules, injections, creams, or any other form of "fake" treatment. They often look like real medicines but do not contain any active drug ingredients. Placebos are used in control groups in clinical trials to compare whether the effect of the test drug exceeds the effect of not receiving the active treatment. The placebo effect is the phenomenon where patients feel an improvement in their symptoms simply because they believe they are receiving a treatment.

Methods and process of this study

This study was a secondary analysis of 6,653 participants aged 18 to 75 years who were divided into three groups: those with MDD (n=2,174), those with MDD (n=451), and those without mental illness (n=4,028). Participants received varenicline, bupropion, a nicotine patch, or a placebo for 12 weeks, supplemented with brief counseling. Safety was assessed by the presence of at least one more severe psychiatric or neurological problem, and efficacy was assessed by the proportion of participants who achieved sustained abstinence from smoking, as confirmed by biochemical testing, during weeks 9 to 12 after treatment.

Research results and drug efficacy analysis

The study found that among all participants, the risk of neuropsychiatric adverse events did not differ significantly between the different medications in the ever-MDD group, the current MDD group, and the non-psychiatric group. However, the difference in the risk of neuropsychiatric adverse events was higher in the MDD group compared with the non-psychiatric group. In the ever-MDD group, the hazard ratios for adverse events were 3.0, 2.1, and 2.1 for varenicline, bupropion, and nicotine patch compared with placebo, respectively.

In the group with active MDD, varenicline had hazard ratios of 2.67 and 2.93 compared with placebo and nicotine patch, respectively.

Varenicline, bupropion, and the nicotine patch were all superior to placebo in the group with ever-MDD. However, the nicotine patch and bupropion were not superior to placebo in the group with current MDD. Varenicline showed good efficacy in both MDD groups and was able to reduce anxiety and depression symptoms in patients with current MDD.

The safety profile of all drugs in the MDD group was generally good. For patients with past or current MDD, varenicline plus counseling may be the best treatment option, given its higher efficacy and similar risk of adverse events. In particular, for patients with current MDD, varenicline can improve mood symptoms while helping to quit smoking.

Scientific smoking cessation treatment can not only improve the physical health of patients with depression, but also promote mental health. Choosing the right medication, combined with psychological counseling and support, will provide a strong guarantee for patients with depression to quit smoking. I hope more people can realize the close connection between smoking and depression, start from themselves, and stay away from tobacco. Let us work together for a healthier and better future!

References:

Kypriotakis G, Cinciripini PM, Green CE, et al. Effects of Varenicline, Bupropion, Nicotine Patch, and Placebo on Treating Smoking Among Persons With Current or Past Major Depressive Disorder: Secondary Analysis of a Double-Blind, Randomized, Placebo-Controlled Trial. Am J Psychiatry(2024). https://psychiatryonline.org/doi/10.1176/appi.ajp.20230855