Smoking cessation in patients with mental health illness

Authors

Roselyn Thom MD (biography, no disclosures), Julius Elefante MD (biography and disclosures) and Martha Ignazewski MD, FRCPC (biography and disclosures)

Dr. Julius Elefante’s disclosures: I have received funding from the US National Institute on Drug Abuse (NIDA) Grant: R25-DA037756 as part of the NIDA-funded research training fellowship offered in partnership with the BC Centre on Substance Use, St. Paul’s Hospital, and the University of British Columbia. I have received educational funds for the development of lectures for UBC, Vancouver Coastal Health, Fraser Health, and Provincial Health Services Authority. Mitigating potential bias: None of these organizations have influenced the content of my work at any stage.

Dr. Martha Ignazewski’s disclosures: Has received honoraria for educational lecture (Indivior) and attendance at a regional advisory meeting (Otsuka/Lundbeck). Mitigating potential bias: Only published trial data are included. Recommendations are consistent with published guidelines (CPS, CFP). Recommendations are consistent with current practice patterns. All potential conflicts are disclosed. Treatments or recommendations in this article are unrelated to products/services/treatments involved in disclosure statements.

What I did before

Tobacco use is a leading cause of mortality among patients with mental health illness (PWMHI), yet addressing smoking cessation in this population remains challenging, with suboptimal assessment, misconceptions about patient willingness to quit and perceived risk about interventions leading to low intervention rates.¹ Research among PWMHI shows that about 50% of patients diagnosed with schizophrenia, bipolar disorder and depression eventually died of tobacco-related causes,² and experience an average reduction in life expectancy of 25 years.¹ Smoking cessation can even improve symptoms of depression and anxiety,³ yet many patients may misinterpret the reduction in nicotine withdrawal symptoms, such as restlessness and anxiety, as evidence that smoking benefits their mental health. Although up to 82% of PWMHI desire to quit,⁴ I previously felt limited in my pharmacotherapy options. Former Food and Drug Administration (FDA) black box warnings around increased depression and suicidal ideation left me uncertain about using varenicline or bupropion in PWMHI. This meant that I was often left with only nicotine replacement for these patients—the least effective of the three pharmacotherapy options for smoking cessation (varenicline, bupropion and nicotine replacement therapy).⁵

What changed my practice

With the recent publication of the BC Guidelines for Tobacco Use Disorder recommending combined pharmacotherapy and counselling as the first-line intervention for smoking cessation, I decided to re-evaluate my hesitations around using varenicline or bupropion for patients with psychiatric diagnoses. The EAGLES trial was the most robust trial of effectiveness and neuropsychiatric safety of pharmacologic strategies for smoking cessation in smokers with and without psychiatric disorders. Findings showed that psychiatric patients using varenicline or bupropion have a 4% increased risk of neuropsychiatric side effects compared to their non-psychiatric counterparts.⁶ However, the nuances of prescribing these medications in the psychiatric population remained somewhat unclear, and these interventions remained underutilized due to concerns about destabilizing patients.

In 2021, the authors of the EAGLES trial published a secondary analysis of the study’s psychiatric cohort,⁷ categorizing participants into three categories based on the number of psychiatric diagnoses: single diagnosis, two comorbid diagnoses, or three or more multimorbid diagnoses. They reanalyzed the data looking for differences in medication compliance, smoking abstinence rates and the risk of neuropsychiatric side effects among these groups. To be included in the original study, patients had to be considered clinically psychiatrically stable for the last six months, with no psychiatric medication changes in the last three months. Patients were then randomized to either 12 weeks of varenicline, bupropion or nicotine replacement therapy (NRT). Below is a summary of the key results:

• Having at least two psychiatric diagnoses was associated with higher smoking dependence and a greater number of previous quit attempts.
• Compliance rates with smoking cessation medications were around 75%, regardless of the degree of psychiatric comorbidity.
• The degree of psychiatric morbidity had no effect on treatment success for all smoking cessation medications (varenicline, bupropion or NRT).
• Psychiatric multimorbidity (i.e. having three or more psychiatric diagnoses) was associated with a higher incidence of neuropsychiatric side effects compared to having two or fewer mental health diagnoses.
• The type of medication received had no effect on the risk of developing neuropsychiatric side effects.

What I do now

As the most robust evidence to date has only looked specifically at PWMHI with at least six months of psychiatric stability, it is warranted to offer pharmacotherapy once this is attained. Ongoing motivation strategies are needed at all stages of acuity.

In the setting of acute treatment when there are several other medication adjustments occurring, it would likely be difficult to ascertain which medications to implicate if neuropsychiatric effects do occur in this period.

I approach tobacco use as a chronic, relapsing condition requiring multifactorial intervention as recommended by the BC Guidelines. I start by asking all patients not just about the number of years they have smoked but, importantly, exploring the role of tobacco in their lives and its consequences, consistent with motivational enhancement principles. Acknowledging the natural history of tobacco use as a relapsing condition helps validate a patient’s previous quit attempt, which is especially important for multimorbid PWMHI, who often have the highest number of previous quit attempts. I also try to provide encouragement by educating patients that research indicates there is a wide range in the number of quit attempts corresponding to sustained smoking cessation.⁸ I emphasize that smoking cessation medications work equally well, regardless of their degree of psychiatric comorbidity or number of previous quit attempts. For all patients, I recommend resources such as QuitNow or the FNHA Talk Tobacco Program for further support.

Since there is no difference between NRT versus bupropion versus varenicline in terms of the risk of developing neuropsychiatric effects, I engage in collaborative treatment planning with patients. I offer patient choice while recommending varenicline as a first-line medication in stable psychiatric patients, as it has the most efficacy in achieving sustained smoking cessation (NNT = 6).⁶ Alongside educating patients about common side effects, including vivid dreams and the relatively low potential for neuropsychiatric effects, I explain how varenicline reduces nicotine withdrawal and cravings through partial agonist activity at the nicotine receptors in the brain with rapid effect. I also ensure that I offer close follow-up to monitor for both efficacy and side effects. This is especially important for patients with multiple psychiatric diagnoses, since they may be more likely to experience adverse neuropsychiatric effects. By combining effective pharmacotherapy with patient psychoeducation, I am hopeful that we can tackle one of the leading causes of silent mortality in patients with mental illness.

Resources for patients

• QuitNow
• Talk Tobacco Program

Resources for health-care providers

• BC Guidelines for Tobacco Use Disorder
  • Enhanced Care Pathways: Tobacco Use Disorder – Cessation Algorithm & Medication Table (also available on Pathways BC)

References

1. Cook BL, Wayne GF, Kafali EN, Liu Z, Shu C, Flores M. Trends in smoking among adults with mental illness and association between mental health treatment and smoking cessation. JAMA. 2014;311(2):172-182. doi:10.1001/jama.2013.284985 (View)
2. Callaghan RC, Veldhuizen S, Jeysingh T, et al. Patterns of tobacco-related mortality among individuals diagnosed with schizophrenia, bipolar disorder, or depression. J Psychiatr Res. 2014;48(1):102-110. doi:10.1016/j.jpsychires.2013.09.014 (View on UBC or View Abstract)
3. ‌Taylor GM, Lindson N, Farley A, et al. Smoking cessation for improving mental health. Cochrane Database Syst Rev. 2021;3(3):CD013522. Published 2021 Mar 9.  doi:10.1002/14651858.CD013522.pub2 (View)
4. Lucksted A, McGuire C, Postrado L, Kreyenbuhl J, Dixon LB. Specifying cigarette smoking and quitting among people with serious mental illness. Am J Addict. 2004;13(2):128-138. doi:10.1080/10550490490436000 (View on UBC or View Abstract)
5. Thombs BD, Traversy G, Reynolds DL, et al. Recommendations on interventions for tobacco smoking cessation in adults in Canada. CMAJ. 2025;197(28):E846-E861. Published 2025 Aug 24. doi:10.1503/cmaj.241584 (View)
6. Evins AE, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with psychotic, anxiety, and mood disorders in the EAGLES trial. J Clin Psychopharmacol. 2019;39(2):108-116. doi:10.1097/JCP.0000000000001015 (View)
7. Correa JB, Lawrence D, McKenna BS, et al. Psychiatric comorbidity and multimorbidity in the EAGLES trial: Descriptive correlates and associations with neuropsychiatric adverse events, treatment adherence, and smoking cessation. Nicotine Tob Res. 2021;23(10):1646-1655. doi:10.1093/ntr/ntab056 (View)
8. Chaiton M, Diemert L, Cohen JE, et al. Estimating the number of quit attempts it takes to quit smoking successfully in a longitudinal cohort of smokers. BMJ Open. 2016;6(6):e011045. Published 2016 Jun 9. doi:10.1136/bmjopen-2016-011045 (View)

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