Previous studies of standard smoking cessation interventions in outpatients with schizophrenia have documented a clear benefit of smoking cessation treatment with moderate cessation rates during treatment but high relapse rates following discontinuation of smoking cessation interventions. In this sample of smokers with schizophrenia or schizoaffective disorder who had a long history of heavy smoking and an average of five prior smoking cessation attempts, 17 of 41 (41.5%) attained seven-day point prevalence abstinence at the end of a three-month treatment regimen with bupropion, transdermal nicotine patch, nicotine polacrilex gum and weekly group cognitive behavioral therapy. All those who attained abstinence with this intervention participated in a relapse prevention program consisting of continuation of pharmacotherapy and a tapering schedule of cognitive behavioral therapy groups for 12 months. Participants attended 81% of groups throughout the 12-month relapse prevention phase suggesting relapse prevention treatment is likely to be well-tolerated and feasible in this population. The findings replicate the work of Horst and colleagues (2005)
who randomized 17 smokers with schizophrenia who successfully attained abstinence after three months of treatment with the transdermal nicotine patch to nine months of continuation single blind transdermal nicotine patch or placebo. After nine months of continuation treatment (month 12), thirty three percent of those receiving the nicotine patch were abstinent whereas none of those who received placebo patch were abstinent.
At the end of 12 months of relapse prevention treatment, 65% had biochemically confirmed seven-day point prevalence abstinence and 59% reported four or more weeks of continuous abstinence. This 35% relapse rate is less than half the 77% relapse rate at 12-months after discontinuation of a similar 12-week smoking cessation intervention of cognitive behavioral therapy, bupropion and dual nicotine replacement therapy in a previous study (Evins et al., 2007
) and the 75% relapse rate three months after discontinuation of cognitive behavioral therapy and bupropion in another study (Evins et al., 2005
). While a relapse rate of 36% at 6 months has been reported in smokers with mental illness following a 12-week smoking cessation intervention (Baker et al., 2006
), this was in a sample in which only 57% had a schizophrenia or schizoaffective disorder, which may account for the lower relapse rates following treatment discontinuation. In the current study, almost one quarter (23.5%) demonstrated prolonged continuous abstinence with continuation therapy, a rate that compares favorably to rates of prolonged abstinence in the general population which rarely exceed 30% with approved pharmacologic and behavioral treatments (Fiore et al., 2008
Although existing research has generally indicated that relapse prevention interventions consisting of extended duration pharmacological and behavioral therapies are not efficacious (c.f.,Agboola et al., 2010
) in promoting sustained abstinence in the general population (Hajek et al., 2009
), abnormalities in neuronal nicotinic acetylcholine receptor expression and function in individuals with schizophrenia suggest a neurobiological rationale for better efficacy of extended duration pharmacotherapy in schizophrenia. Nicotinic acetylcholine receptor expression and function are abnormally low in individuals with schizophrenia, independent of smoking status (Breese et al., 2000
; Durany et al., 2000
). Thus, though these receptors are upregulated to some extent with nicotine exposure, nicotine receptor number and function are not expected to return to a normal baseline after smoking cessation among individuals with schizophrenia who attain abstinence. Nicotine has been shown to ameliorate cognitive and neurophysiologic abnormalities associated with schizophrenia (Adler, Hoffer, Griffith, Waldo, & Freedman, 1992
; Adler, Hoffer, Wiser, & Freedman, 1993
; Avila, Sherr, Hong, Myers, & Thaker, 2003
; Barr, et al., 2007
; Julbelt et al., 2009, Smith et al., 2008). Because nicotine may confer greater cognitive benefit to smokers with schizophrenia than to smokers without this psychiatric illness, there may be a stronger drive to return to smoking once abstinent among individuals with schizophrenia than in the general population. Longer-term nicotine dependence treatment could potentially compensate for these abnormalities and by doing so, promote continued abstinence among individuals with schizophrenia. This hypothesis will need to be tested in future trials.
The major limitations of this study are the small sample size and lack of control groups. Another limitation is reliance on self-report for 4-week continuous abstinence rates later in the study when group sessions were less frequent, as biochemical validation of abstinence was performed only at group sessions. In addition, because the intervention had multiple components, it is not possible to identify which component(s) contributed to the sustained abstinence rates. Also, information was not systematically collected on factors that contributed to relapse, such as exposure to smoking-related cues, permission-giving beliefs, or suboptimal adherence to psychiatric or smoking cessation medications. Although we assessed self-report of medication adherence and attempted to count pills and unused nicotine replacement therapy, participants were poorly compliant with this component of the protocol. Additionally, although we did not choose to focus on smokers with other co-occurring substance use disorders in the current study, future work should consider this group given evidence that this group: comprises a large percentage of individuals with schizophrenia, is motivated to stop smoking cigarettes, and rarely receives evidence-based interventions for smoking cessation (Ferron et al., 2011
). Notwithstanding these limitations, the results suggest that relapse prevention treatment may be feasible and may result in higher sustained abstinence rates and lower relapse rates in recently abstinent smokers with schizophrenia. Larger, controlled trials are warranted to further investigate the effect of extended duration treatment for prevention of relapse to smoking in individuals with schizophrenia, as well as to better estimate the optimal components and duration of this treatment in order to maximize sustained smoking abstinence rates and improve health outcomes in this population. If confirmed in larger trials, the results of this study may provide a rational treatment that in clinical practice could reduce the heavy burden of smoking-related morbidity and mortality in this population.