Comparison of Cardiovascular Risks following Smoking Cessation Treatments Using Varenicline vs. NRT among Schizophrenic Smokers
Main Article Content
Abstract
Background: Schizophrenic patients have a lot higher smoking rates when compared to people in the general population. A variety of pharmaceutical cessation aids are available, which include nicotine replacement therapy (NRT), Bupropion SR, and Varenicline. Our objective was to assess which cessation medication would have lower risks in developing risk factors of cardiovascular diseases.
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. 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 hazard ratio of developing cardiovascular risks was assessed using Cox proportional hazards regression model after controlling for other covariates.
Results: A total of 580 patients were included in our cohort. Among those, nearly half (n=276, 47.59%) developed one or more criteria of the metabolic syndromes. We found that smokers who were prescribed NRT were less likely to develop metabolic syndromes as compared to those who were prescribed Varenicline.
Conclusions: Physicians are advised to carefully weigh the risks against the benefits before prescribing cessation medications since risks for metabolic syndromes were found to be very high. Healthcare providers should monitor patients’ lab data regularly as this minority population is under higher risks.
Article Details
Copyright (c) 2017 Wu IH, et al.

This work is licensed under a Creative Commons Attribution 4.0 International License.
Evins AE, Cather C, Culhane MA, Birnbaum A, Horowitz J, et al. A 12-week double-blind, placebo controlled study of bupropion SR added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia. J Clin Psychopharmacol. 2007; 27: 380-386. Ref.: https://goo.gl/T6KsxS
Ferchiou A, Szöke A, Laguerre A, Méary A, Leboyer M, et al. Exploring the relationships between tobacco smoking and schizophrenia in first-degree relatives. Psychiatry Res. 2012; 200: 674-678. Ref.: https://goo.gl/sBbFCb
George TP, Vessicchio JC, Sacco KA, Weinberger AH, Dudas MM, et al. A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia. Biological Psychiatry. 2008; 63: 1092-1096. Ref.: https://goo.gl/34Sxoh
Lo S, Heishman SJ, Raley H, Wright K, Wehring HJ, et al. Tobacco craving in smokers with and without schizophrenia. Schizophrenia Res. 2011; 127: 241-245. Ref.: https://goo.gl/kJ9FJX
Leonard S, Mexal S, Freedman R. Smoking, genetics and schizophrenia: evidence for self medication. J Dual Diagnosis. 2007; 3: 43-59. Ref.: https://goo.gl/ee3xqr
Tsoi DT, Porwal M, Webster AC. Efficacy and safety of bupropion for smoking cessation and reduction in schizophrenia: systematic review and meta-analysis.British J Psychiatry. 2010; 196: 346-353. Ref.: https://goo.gl/zTx4rB
7.Pierce JP, Gilpin EA. Impact of over-the-counter sales on effectiveness of pharmaceutical aids for smoking cessation. JAMA. 2002; 288: 1260-1264. Ref.: https://goo.gl/o1Esp6
Jimenez-Ruiz C, Berlin I, Hering T. Varenicline: a novel pharmacotherapy for smoking cessation. Drugs. 2009; 69: 1319-1338. Ref.: https://goo.gl/8roqNE
Fava M, Rush AJ, Thase ME, Clayton A, Stahl SM, et al. 15 years of clinical experience with bupropion HCl: from bupropion to bupropion SR to bupropion XL. Primary Care Com J Clinical Psyc. 2005; 7: 106-113. Ref.: https://goo.gl/pkbryL
Fiore, Michael C. Treating tobacco use and dependence. Clinical practice guideline. DIANE Publishing. 2008; Ref.: https://goo.gl/XpbSLR
Singh S, Loke YK, Spangler JG, Furberg CD. Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ. 2011; 183: 1359-1366. Ref.: https://goo.gl/pU4Jhf
Erhardt L. Cigarette smoking: an undertreated risk factor for cardiovascular disease. Atherosclerosis. 2009; 205: 23-32. Ref.: https://goo.gl/E5ddsG
Filozof C, Pinilla F, Fernández-Cruz A. Smoking cessation and weight gain. Obesity Reviews. 2004; 5: 95-103. Ref.: https://goo.gl/9eeXaa
Parsons AC, Shraim M, Inglis J, Aveyard P, Hajek P. Interventions for preventing weight gain after smoking cessation. Cochrane Database Syst Rev. 2009; 1. Ref.: https://goo.gl/kR6Qzk
Yeh HC, Duncan BB, Schmidt MI, Wang NY, Brancati FL. Smoking, Smoking Cessation, and Risk for Type 2 Diabetes Mellitus A Cohort Study. Ann Internal Medicine. 2010; 152: 10-17. Ref.: https://goo.gl/rdgtMA
Janzon E, Hedblad B, Berglund G, Engström G. Changes in blood pressure and body weight following smoking cessation in women. J iIternal Med. 2004; 255: 266-272. Ref.: https://goo.gl/reut8M
Gerace TA, Hollis J, Ockene JK, Svendsen K. Smoking cessation and change in diastolic blood pressure, body weight, and plasma lipids. Preventive Medicine. 1991; 20: 602-620. Ref.: https://goo.gl/2KqfuQ
Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, et al. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophrenia Res. 2010; 123: 225-233. Ref.: https://goo.gl/F6uc7v
Chakos M, Lieberman J, Hoffman E, Bradford D, Sheitman B. Effectiveness of second-generation antipsychotics in patients with treatment-resistant schizophrenia: a review and meta-analysis of randomized trials. FOCUS: The J Lifelong Learning in Psy. 2004; 2: 111-121. Ref.: https://goo.gl/n4GsTm
Benowitz NL. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Ann Pharmacol Toxicol. 2009; 49: 57. Ref.: https://goo.gl/UwUvFA
Evins AE, Cather C, Deckersbach T, Freudenreich O, Culhane MA, et al. A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia. J Clinical Psyc. 2005; 25: 218-225. Ref.: https://goo.gl/DM1YGN
Zammit S, Allebeck P, David AS, Dalman C, Hemmingsson T, et al. A longitudinal study of premorbid IQ score and risk of developing schizophrenia, bipolar disorder, severe depression, and other nonaffective psychoses. Arch General Psy. 2004; 61: 354-360. Ref.: https://goo.gl/39AoQh
Lund BC, Perry PJ, Brooks JM, Arndt S. Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach. Arch General Psyc. 2001; 58: 1172. Ref.: https://goo.gl/L2Djw1
Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, et al. The Metabolic Syndrome and Cardiovascular RiskA Systematic Review and Meta-Analysis. J American College of Card. 2010; 56: 1113-1132. Ref.: https://goo.gl/fXUFCm
Rigotti NA, Pipe AL, Benowitz NL, Arteaga C, Garza D, et al. Efficacy and Safety of Varenicline for Smoking Cessation in Patients With Cardiovascular Disease A Randomized Trial. Circulation. 2010; 121: 221-229. Ref.: https://goo.gl/LgwNxF
Cleland JG, Gemmell I, Khand A, Boddy A. Is the prognosis of heart failure improving?. European J Heart Failure. 1999; 1: 229-241. Ref.: https://goo.gl/ug1w5u
Lambert BL, Cunningham FE, Miller DR, Dalack GW, Hur K. Diabetes risk associated with use of olanzapine, quetiapine, and risperidone in veterans health administration patients with schizophrenia. Am I Epidemiol. 2006; 164: 672-681. Ref.: https://goo.gl/EHSSYA
Lin HC, Chien CW, Ho JD. Herpes zoster ophthalmicus and the risk of stroke A population-based follow-up study. Neuro. 2010; 74: 792-797. Ref.: https://goo.gl/LBd4Fy
de Leon J, Correa JC, Ruaño G, Windemuth A, Arranz MJ, et al. Exploring genetic variations that may be associated with the direct effects of some antipsychotics on lipid levels. Schizophrenia Res. 2008; 98: 40-46. Ref.: https://goo.gl/fBPdy6
Lambert BL, Chou CH, Chang KY, Tafesse E, Carson W. Antipsychotic exposure and type 2 diabetes among patients with schizophrenia: a matched case-control study of California Medicaid claims. Pharma Drug Saf. 2005; 14: 417-425. Ref.: https://goo.gl/Lwsj2W
De Hert M, Schreurs V, Sweers K, Van Eyck D, Hanssens L, et al. Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: a retrospective chart review. Schizophrenia Res. 2008; 101: 295-303. Ref.: https://goo.gl/7mijz1
Galassi A, Reynolds K, He J. Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. The Am J Med. 2006; 119: 812-819. Ref.: https://goo.gl/ehN3CD
Stone NJ, Saxon D, Approach to treatment of the patient with metabolic syndrome: lifestyle therapy. The Am I Cardiol. 2005; 96: 15-21. Ref.: https://goo.gl/tdc1CA
Gadde KM, Xiong GL. Bupropion for weight reduction. Expert Rev Neurotherapeutics. 2007; 7: 17-24. Ref.: https://goo.gl/LgqXjQ
Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, et al. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. New England J Med. 1999; 340: 685-691. Ref.: https://goo.gl/eKoVD5
Paeratakul S, Lovejoy JC, Ryan DH, Bray GA. The relation of gender, race and socioeconomic status to obesity and obesity comorbidities in a sample of US adults. Int J Obesity & Rel Metabolic Dis. 2002; 26: 1205-1210. Ref.: https://goo.gl/iirb5a
Sullivan PW, Morrato EH, Ghushchyan V, Wyatt HR, Hill JO. Obesity, inactivity, and the prevalence of diabetes and diabetes-related cardiovascular comorbidities in the US, 2000–2002. Diabetes Care. 2005; 28: 1599-1603. Ref.: https://goo.gl/gW2j5d
Wang G, Zheng ZJ, Heath G, Macera C, Pratt M, et al. Economic burden of cardiovascular disease associated with excess body weight in US adults. Am J Preventive Med. 2002; 23: 1-6. Ref.: https://goo.gl/JpVZYL
Pilote L, Dasgupta K, Guru V, Humphries KH, McGrath J, et al. A comprehensive view of sex-specific issues related to cardiovascular disease. CMAJ. 2007; 176: 1-44. Ref.: https://goo.gl/aCYmbB
Vermeire E, Hearnshaw H, Van Royen P, Denekens J. Patient adherence to treatment: three decades of research. A comprehensive review. J Clin Pharmacy Ther. 2001; 26: 331-342. Ref.: https://goo.gl/NJU4Bk