Smoking is one of the leading causes of morbidity and mortality in the United States and worldwide.1 Nearly 41% of smokers report having a current mental health diagnosis,2 and 60% of smokers report a mental health diagnosis at some point in their lifetimes.3 Adults with mental illness have a smoking rate that is 70% higher than adults with no mental illness4 and die approximately 25 years earlier than the general population, due largely to their high rates of substance use—including cigarette smoking.5 Quit rates among smokers with mental illness are significantly lower than those among the general population.2
Individuals with severe psychotic illness (schizophrenia, schizoaffective disorder, and bipolar disorder with psychotic features) have higher rates of smoking abuse than those with other mental illnesses. A recent study assessed the comorbidity of cigarette smoking and severe psychotic disorders in patients drawn from the Genomic Psychiatry cohort (a multiethnic sample consisting of 9,142 individuals with severe psychotic disorders, and 10,195 population control individuals).5 The researchers found “markedly higher” cigarette use than in the general population “at a rate that far exceeded previous estimates based on assessments in individuals with mild mental illness.”5 The researchers concluded that their findings highlight “the need for targeting substance use, specifically among individuals with severe psychotic illness, because protective influences may not carry over from the general population.”5
Pharmacologic Treatment Options for Smokers with Mental Illness
Seven FDA-approved pharmacologic interventions are available to aid in smoking cessation—five nicotine replacement therapies (NRT), bupropion, and varenicline.6 A recent meta-analysis found higher rates of smoking cessation associated with NRT (17.6% and bupropion (19.1%) compared with placebo (10.6%). Varenicline (27.6 percent) and combination NRT (31.5%) were most effective for achieving smoking cessation. None of the therapies was associated with an increased rate of serious adverse events.7,8
In 2009, the US FDA issued a black box warning for varenicline regarding neuropsychiatric events, based on data from randomized controlled trials and a large Department of Defense (DOD) observational study of patients receiving varenicline or NRT.9 A recent re-analysis of data from these trials (N=8027) and the DOD (N= 35,800) found no evidence that varenicline is associated with adverse neuropsychiatric events. Moreover, the evidence supported superior efficacy of varenicline, relative to placebo and bupropion. However, the authors acknowledged that current or past psychiatric illness increased the risk of neuropsychiatric events equally in all patients.9 By contrast, a British study of 119,654 patients treated with either bupropion or varenicline found no difference in risk of suicidal behavior in varenicline versus NRT products.10
Two recent trials have looked specifically at varenicline as maintenance therapy for smoking cessation in patients with mental illness. Evins et al compared maintenance varenicline versus standard treatment in achieving tobacco abstinence in patients with serious mental illness. The researchers found that abstinence at one year was three times higher among those assigned to maintenance varenicline treatment (60 percent) versus those assigned to placebo (19%). Varenicline was well-tolerated, with no significant psychiatric adverse events.
A study of varenicline maintenance treatment in adults with stably treated current or past depression found that varenicline-treated participants had higher continuous abstinence rates versus placebo at weeks nine to 52 (20.3% vs.10.4% respectively), with no clinically relevant differences between groups in suicidal ideation or behavior, and no overall worsening of depression or anxiety.11 And NRT has been found helpful in reducing agitation in patients with schizophrenia in the emergency department,12 although a meta-analysis failed to find convincing evidence of its utility in longer-term smoking cessation.13