Schizophrenia and Nicotine Dependence: What Psychopharmacological Treatment Options are Available for the Duo Perturbationes?

Author(s): Yoong Mei Theng, Suzaily Wahab*, Noor Alaudin A. Wahab, Hatta Sidi, Srijit Das.

Journal Name: Current Drug Targets

Volume 20 , Issue 2 , 2019

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Graphical Abstract:


Nicotine dependence has progressively become a foremost community health interest in both the developed and developing nations due to the economic burden and health-related problems. Smoking was significantly higher among patients with schizophrenia in comparison to the general population. Nicotine dependence is not only associated with public stress, but among patients with schizophrenia, smoking brings major challenges to the management. Nicotine may diminish the therapeutic efficacy of the bioavailability of the psychopharmacological agents in-vivo. These duo perturbations, i.e. two clinical conditions co-existed may prevent psychotic symptoms remission among patients suffering from schizophrenia who smoke at the same time. The aim of this review was to highlight the role of pharmacological treatment options and strategies for patients with nicotine dependence in schizophrenia with emphasis on the underlying neurobiological process. The role of nicotine replacement therapy, i.e. norepinephrine-dopamine reuptake inhibition (NDRI) e.g. bupropion and selective partial agonist of α4β2 and full α7-nicotinic acetylcholine receptor e.g. varenicline was deliberated. An ideal choice of drug targets for patients with schizophrenia with nicotine dependence is pivotal to foster a better therapeutic alliance.

Keywords: Nicotine dependence, schizophrenia, treatment options, smoking, psychoactive agents, drug targets.

World Health OrganizationWHO report on the global tobacco epidemic, 2013: enforcing bans on tobacco advertising, promotion and sponsorship. World Health Organization 2013.
Prochaska JJ. Smoking and mental illness-breaking the link. N Engl J Med 2011; 365(3): 196-8.
Sadock BJ, Sadock VA. Kaplan and Sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry. Lippincott Williams & Wilkins 2014; pp. pp. 680-685.
Laursen TM, Munk-Olsen T, Vestergaard M. Life expectancy and cardiovascular mortality in persons with schizophrenia. Curr Opin Psychiatry 2012; 25(2): 83-8.
Himelhoch S, Lehman A, Kreyenbuhl J, Daumit G, Brown C, Dixon L. Prevalence of chronic obstructive pulmonary disease among those with serious mental illness. Am J Psychiatry 2004; 161(12): 2317-9.
Dickerson F, Origoni A, Schroeder J, et al. Mortality in schizophrenia and bipolar disorder: clinical and serological predictors. Schizophr Res 2016; 170: 177-83.
Desai HD, Seabolt J, Jann MW. Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective. CNS Drugs 2001; 15: 469-94.
Tidey JW, Rohsenow DJ. Smoking expectancies and intention to quit in smokers with schizophrenia, schizoaffective disorder and non-psychiatric controls. Schizophr Res 2009; 115(2-3): 310-6.
Williams JM. Eliminating tobacco use in mental health facilities: patients’ rights, public health, and policy issues. JAMA 2008; 299: 571-3.
Ragg M, Gordon R, Ahmed T, Allan J. The impact of smoking cessation on schizophrenia and major depression. Australas Psychiatry 2013; 21: 238-45.
George TP, Ziedonis DM, Feingold A, et al. Nicotine transdermal patch and atypical antipsychotic medications for smoking cessation in schizophrenia2000 Am J Psychiatry 2000; 157(1): 835-42.
Evins AE, Cather C, Culhane MA, 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(4): 380-6.
Medicines Information Centre, Pharmacy Department, Smoking and Drug Interactions, Mersey Care NHS Trust. http:// Date of access: 9 August 2017
Grizzell JA, Echeverria V. New insights into the mechanisms of action of cotinine and its distinctive effects from nicotine. Neurochem Res 2015; 40(10): 2032-46.
Dickerson F, Stallings CR, Origoni AE, et al. Cigarette smoking among persons with schizophrenia or bipolar disorder in routine clinical settings, 1999-2011. Psychiatr Serv 2013; 64(1): 44-50.
Benowitz NL. Nicotine addiction. N Engl J Med 2010; 362(24): 2295-303.
Benowitz NL, Henningfield JE. Establishing a nicotine threshold for addiction--The implications for tobacco regulation. N Engl J Med 1994; 331(2): 123-5.
Balfour DJ. The psychobiology of nicotine dependence. Eur Respir Rev 2008; 17(110): 172-81.
Stahl SM. Stahl's essential psychopharmacology: Neuroscientific basis and practical applications. Cambridge university press; 2013 Apr 11.
Kelley AE. Memory and addiction: Shared neural circuitry and molecular mechanisms. Neuron 2004; 44(1): 161-79.
Kelly C, McCreadie R. Cigarette smoking and schizophrenia. Adv Psychiatr Treat 2013; 15(5): 322-7.
de Leon J, Dadvand M, Canuso C, White AO, Stanilla JK, Simpson GM. Schizophrenia and smoking: An epidemiological survey in a state hospital. Am J Psychiatry 1995; 152(3): 453-5.
de Leon J, Tracy J, McCann E, McGrory A, Diaz FJ. Schizophrenia and tobacco smoking: A replication study in another US psychiatric hospital. Schizophr Res 2002; 56(1-2): 55-65.
Prochaska JJ, Benowitz NL. The past, present, and future of nicotine addiction therapy. Annu Rev Med 2016; 67: 467-86.
de Leon J, Diaz FJ. Genetics of schizophrenia and smoking: An approach to studying their comorbidity based on epidemiological findings. Hum Genet 2012; 131(6): 877-901.
Hall SE, Prochaska JJ. Clinical issues and strategies associated with smoking cessation. Psychiatr Times 2015; 32(3): 57.
de Leon J, Diaz FJ, Rogers T, Browne D, Dinsmore L. Initiation of daily smoking and nicotine dependence in schizophrenia and mood disorders. Schizophr Res 2002; 56(1-2): 47-54.
Manzella F, Maloney SE, Taylor GT. Smoking in schizophrenic patients: A critique of the self-medication hypothesis. World J Psychiatry 2015; 5(1): 35.
Schwartz K, Iancu I, Stryjer R, et al. Reduced platelet vesicular monoamine transporter density in smoking schizophrenia patients. Eur Neuropsychopharmacol 2005; 15: 557-61.
Annamalai A, Singh N, O’Malley SS. Focus: Addiction: Smoking use and cessation among people with serious mental illness. Yale J Biol Med 2015 Sep; 88(3): 271.
Vokes NI, Bailey JM, Rhodes KV. “Should I give you my smoking lecture now or later?” Characterizing emergency physician smoking discussions and cessation counseling. Ann Emerg Med 2006; 48(4): 406-14.
Williams JM, Ziedonis D. Addressing tobacco among individuals with a mental illness or an addiction. Addict Behav 2004; 29(6): 1067-83.
Himelhoch S, Riddle J, Goldman HH. Barriers to implementing evidence-based smoking cessation practices in nine community mental health sites. Psychiatr Serv 2014; 65(1): 75-80.
Mitchell JE, Dahlgren LA. Prevalence of smoking among psychiatric outpatients. Am J Psychiatry 1986; 143(8): 993-7.
Kalman D, Morissette SB, George TP. Co-morbidity of smoking in patients with psychiatric and substance use disorders. Am J Addict 2005; 14(2): 106-23.
García-Portilla MP, Bobes J. Smoking cessation programs for persons with schizophrenia: An urgent unmet need. Rev Psiquiatr Salud Ment 2016; 9(4): 181.
de Leon J, Diaz FJ. A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophr Res 2005; 76(2): 135-57.
Paolini M, De Biasi M. Mechanistic insights into nicotine withdrawal. Biochem Pharmacol 2011; 82(8): 996-1007.
Tuesta LM, Fowler CD, Kenny PJ. Recent advances in understanding nicotinic receptor signaling mechanisms that regulate drug self-administration behavior. Biochem Pharmacol 2011; 82(8): 984-95.
Dawe S, Gray JA, Russell MA, Gerda C. Nicotine intake in smokers increases following a single dose of haloperidol. Psychopharmacology (Berl) 1995; 117(1): 110-5.
Zhang XY, Liang J, Xiu MH, et al. Cigarette smoking in male patients with chronic schizophrenia in a Chinese population: prevalence and relationship to clinical phenotypes. PLoS One 2012; 7(2): e30937.
Stead LF, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2012; 11(11): CD000146.
Tønnesen P, Lauri H, Perfekt R, Mann K, Batra A. Efficacy of a nicotine mouth spray in smoking cessation: a randomised, double-blind trial. Eur Respir J 2012; 40(3): 548-54.
Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta‐analysis. Cochrane Database Syst Rev 2013; (5): CD009329.
Ziedonis DM, George TP. Schizophrenia and nicotine use: Report of a pilot smoking cessation program and review of neurobiological and clinical issues. Schizophr Bull 1997; 23(2): 247-54.
Addington J, El-Guebaly N, Campbell W, Hodgins DC, Addington D. Smoking cessation treatment for patients with schizophrenia. Am J Psychiatry 1998; 155(7): 974-5.
Ezat WS, Selahuddeen AA, Aljunid SM, Zarihah Z. Patterns and predictors of smoking cessation among smokers attending smoking cessation clinics in Peninsular Malaysia. Jurnal Kesihatan Masyarakat 2008; 14(1): 17-23.
Hughes JR, Stead LF, Hartmann‐Boyce J, Cahill K, Lancaster T. Antidepressants for smoking cessation. The Cochrane Libr 2014.
Cinciripini PM, Robinson JD, Karam-Hage M, et al. Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on prolonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal. JAMA Psychiatry 2013; 70(5): 522-33.
Rau KS, Birdsall E, Hanson JE, et al. Bupropion increases striatal vesicular monoamine transport. Neuropharmacology 2005; 49(6): 820-30.
Weiner E, Ball MP, Buchholz AS, et al. Bupropion sustained release added to group support for smoking cessation in schizophrenia: a new randomized trial and a meta-analysis. J Clin Psychiatry 2012; 95-102.
Tsoi DT, Porwal M, Webster AC. Efficacy and safety of bupropion for smoking cessation and reduction in schizophrenia: Systematic review and meta-analysis. Br J Psychiatry 2010; 196(5): 346-53.
Turner JR, Castellano LM, Blendy JA. Parallel anxiolytic-like effects andupregulation of neuronal nicotinic acetylcholine receptors following chronic nicotine and varenicline. Nicotine Tob Res 2011; 13(1): 41-6.
Smith RC, Amiaz R, Si TM, et al. Varenicline effects on smoking, cognition, and psychiatric symptoms in schizophrenia: A double-blind randomized trial. PLoS One 2016; 11(1): e0143490.
Gonzales D, Rennard SI, Nides M, et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 2006; 296(1): 47-55.
Jorenby DE, Hays JT, Rigotti NA, et al. Varenicline Phase 3 Study Group. Efficacy of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 2006; 296(1): 56-63.
Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2012; 4: CD006103.
Mills EJ, Wu P, Lockhart I, et al. Comparisons of high-dose and combination nicotine replacement therapy, varenicline, and bupropion for smoking cessation: a systematic review and multiple treatment meta-analysis. Ann Med 2012; 44(6): 588-97.
Eisenberg MJ, Filion KB, Yavin D, et al. Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled trials. CAMJ 2008; 179(2): 135-44.
Gibbons RD, Mann JJ. Varenicline, smoking cessation, and neuropsychiatric adverse events. Am J Psychiatry 2013; 170(12): 1460-7.
Freedman R. Exacerbation of schizophrenia by varenicline. Am J Psychiatry 2007; 164(8): 1269.
Kohen I, Kremen N. Varenicline-induced manic episode in a patient with bipolar disorder. Am J Psychiatry 2007; 164(8): 1269-70.
Nino-Gomez J, Carlini S, Nemani K, et al. Safety and efficacy of varenicline in schizophrenia: Preliminary data from 12-week trial. InAbstract presented at the 16th Annual Meeting of the Society for Research on Nicotine and Tobacco 2010 Feb 24.;
Ismail Z, Syms J, Blumberger D, George TP. Varenicline induced polydipsia and hyponatremia in a patient with schizophrenia. Schizophr Res 2010; 119: 268.
Evins AE, Goff DC. Varenicline treatment for smokers with schizophrenia: A case series. J Clin Psychiatry 2008; 69(6): 1016.
Patterson F, Jepson C, Strasser AA, et al. Varenicline improves mood and cognition during smoking abstinence. Biol Psychiatry 2009; 65(2): 144-9.
Ebbert JO, Wyatt KD, Hays JT, Klee EW, Hurt RD. Varenicline for smoking cessation: efficacy, safety, and treatment recommendations. Patient Prefer Adherence 2010; 4: 355.
Smith RC, Lindenmayer JP, Davis JM, et al. Cognitive and antismoking effects of Varenicline in patients with schizophrenia or schizoaffective disorder. Schizophr Res 2009; 110(1-3): 149-55.
Weiner E, Buchholtz A, Coffay A, et al. Varenicline for smoking cessation in people with schizophrenia: a double blind randomized pilot study. Schizophr Res 2011; 129(1): 94.
Pachas GN, Cather C, Pratt SA, et al. Varenicline for smoking cessation in schizophrenia: Safety and effectiveness in a 12-week open-label trial. J Dual Diagn 2012; 8(2): 117-25.
Matthews AM, Wilson VB, Mitchell SH. The role of antipsychotics in smoking and smoking cessation. CNS Drugs 2011; 25(4): 299-315.
McEvoy JP, Freudenreich O, Levin ED, Rose JE. Haloperidol increases smoking in patients with schizophrenia. Psychopharmacology (Berl) 1995; 119(1): 124-6.
Chatterton R, Sanderson L, Van Leent S, Plant K. Does clozapine affect smoking rates? Aust N Z J Psychiatry 1998; 32(6): 890-1.
George TP, Sernyak MJ, Ziedonis DM, Woods SW. Effects of clozapine on smoking in chronic schizophrenic outpatients. J Clin Psychiatry 1995; 56(8): 344-6.
McEvoy J, Freudenreich O, McGee M, VanderZwaag C, Levin E, Rose J. Clozapine decreases smoking in patients with chronic schizophrenia. Biol Psychiatry 1995; 37: 550-2.
Palazzolo DL. Electronic cigarettes and vaping: a new challenge in clinical medicine and public health. A literature review. Front Public Health 2013; 1: 56.
Caponnetto P, Auditore R, Russo C, Cappello GC, Polosa R. Impact of an electronic cigarette on smoking reduction and cessation in schizophrenic smokers: a prospective 12-month pilot study. Int J Environ Res Public Health 2013; 10(2): 446-61.
Orr KK, Asal NJ. Efficacy of electronic cigarettes for smoking cessation. Ann Pharmacother 2014; 48(11): 1502-6.

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Article Details

Year: 2019
Page: [173 - 181]
Pages: 9
DOI: 10.2174/1389450118666171017163741
Price: $58

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