Comparative Effectiveness of Smoking Cessation Medications among Schizophrenic Smokers



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BACKGROUND: Schizophrenic patients have higher smoking rates when compared to people in the general population. Additionally, they tend to have much lower smoking cessation rates and higher nicotine dependence level. A variety of pharmaceutical cessation aids are available, which include nicotine replacement therapy (NRT), Bupropion SR, and Varenicline.

OBJECTIVES: To compare different pharmacotherapies in smoking cessation and to examine which medication could lead to a higher smoking abstinence rate for both short (12 weeks + 4 weeks) and long term (one year) among schizophrenic patients (1st objective). Further, to assess which cessation medication exposure would have lower risks in developing risk factors of cardiovascular diseases (2nd objective) and suicide behaviors/attempts (3rd objective).

METHODS: A population-based retrospective cohort study was conducted using the General Electric (GE) electronic medical record database (1995 – 2011). The cohort consisted of patients with a diagnosis of schizophrenia or schizoaffective disorder (ICD-9 code 295.00-295.99) and who had newly initiated use of any smoking cessation medication. This cohort was then followed for 12 weeks (up to 16 weeks) and 1 year to observe their smoking status at short and long term after cessation treatment. Multivariate logistic regression models were used to determine which cessation medication was more effective in quitting. For our second objective, we excluded our cohort who (1) were not prescribed atypical antipsychotics and (2) already had diagnosis of diabetes, hyperlipidemia or hypertension prior to index date. Follow up period was from 12 weeks onwards index date up to one year. The relative risk of developing cardiovascular risks was assessed using Cox proportional hazards regression model after controlling for other covariates. Similarly, for our third objective, relative risk of suicide behaviors/attempts risks was assessed using Cox proportional hazards regression model with one year follow up from index date.

RESULTS: The sample comprised of a total of 3,976 schizophrenic smokers who had used at least one type of cessation medication. Abstinence rate was about 18.02% at week 12 and 17.20% at year 1. Among those who quit at 12th week, about 75.22% of the quitting effect sustained at 1 year. We did not find any differences between cessation medications after 12 weeks and 1 year of cessation treatment. Other predictors we found that were associated with quitting included being older, white, whose residential area was in the west part of U.S., and without smoking counseling. Patients who reported not smoking at week 12 and who did not receive cessation medications during week 16 to year 1 were more likely to be abstinent from smoking at year 1. After excluding those who had diabetes, hyperlipidemia, or hypertension prior to cessation medications, we had 580 schizophrenic smokers. Among those, nearly half (n=276, 47.59%) developed one or more criteria of the metabolic syndromes within just one year after the treatment. We found that smokers who were prescribed NRT were less likely to develop metabolic syndromes as compared to those who were prescribed Varenicline. Rates of suicide ideations/behaviors were 2.65% within one year after the exposure. We did not find any differences in leading suicide between the medications. The only predictor we found to be associated with suicide was comorbidity index.

CONCLUSIONS/IMPORTANCE: This was the first retrospective study that examined comparative effectiveness of smoking cessation medications among schizophrenic smokers. Predictors identified in this study should be considered when designing smoking cessation interventions. This minority population may need more tailored approaches to achieve a successful cessation outcome. Further, physicians are advised to carefully weigh the risks against the benefits before prescribing cessation medications since risks for metabolic syndromes and suicide were found to be very high. Healthcare providers should monitor patients’ lab data regularly and pay close attention to all the possible signs of suicide thoughts among this high risk population, especially those who are on pharmacological cessation intervention attempting to quit smoking.



Smoking cessation, Schizophrenia, Nicotine replacement therapy (NRT), Bupropion, Varenicline