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Published in: European Archives of Psychiatry and Clinical Neuroscience 3/2015

01-04-2015 | Original Paper

Varenicline for smoking cessation in people with schizophrenia: systematic review and meta-analysis

Authors: Taro Kishi, Nakao Iwata

Published in: European Archives of Psychiatry and Clinical Neuroscience | Issue 3/2015

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Abstract

We performed an updated meta-analysis of randomized double-blind placebo-controlled trials (RCTs) on the effects of varenicline adjuvant therapy for smoking cessation in people with schizophrenia, on the basis of a previous meta-analysis (Tsoi in Cochrane Database Syst Rev 2:CD007253, 2013). We searched PubMed, the Cochrane Library databases, and PsycINFO up to August 1, 2014. RCTs comparing varenicline adjuvant therapy with placebo in schizophrenia were included. The risk ratio (RR), number needed to harm (NNH), and standardized mean differences with its 95 % confidence interval (CI) were used. Seven studies (total n = 439), including 6 with only schizophrenia (total n = 352), 1 with both schizophrenia (n = 77) and bipolar disorder (n = 10), were included. Varenicline was not superior to placebo in smoking cessation (RR = 0.79, 95 % CI 0.58–1.08, p = 0.14, 5 RCTs, n = 322). Varenicline failed to show its superiority to placebo for overall, positive, negative, and depressive symptoms. Moreover, there was no significant difference in the discontinuation rate due to all causes, clinical deterioration, or side effects between varenicline and placebo. Although varenicline caused less abnormal dreams/nightmares than placebo (RR = 0.47, 95 % CI 0.22–0.99, p = 0.05, NNH = not significant, 4 RCTs, n = 288), it caused more nausea (RR = 1.79, 95 % CI 1.20–2.67, p = 0.004, NNH = 6, p = 0.004, 6 RCTs, n = 417). We detected no significant difference in suicidal ideation and depression between varenicline and placebo. Our results suggest that although varenicline adjuvant therapy is well tolerated, varenicline is not superior to placebo for smoking cessation in people with schizophrenia. Because of the limited sample sizes of the available studies, future studies will require larger samples to ensure that these findings are generalizable.
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Literature
1.
go back to reference Addington D, Addington J, Schissel B (1990) A depression rating scale for schizophrenics. Schizophr Res 3:247–251CrossRefPubMed Addington D, Addington J, Schissel B (1990) A depression rating scale for schizophrenics. Schizophr Res 3:247–251CrossRefPubMed
2.
go back to reference Allen MH, Debanne M, Lazignac C, Adam E, Dickinson LM, Damsa C (2011) Effect of nicotine replacement therapy on agitation in smokers with schizophrenia: a double-blind, randomized, placebo-controlled study. Am J Psychiatry 168:395–399CrossRefPubMed Allen MH, Debanne M, Lazignac C, Adam E, Dickinson LM, Damsa C (2011) Effect of nicotine replacement therapy on agitation in smokers with schizophrenia: a double-blind, randomized, placebo-controlled study. Am J Psychiatry 168:395–399CrossRefPubMed
3.
go back to reference Andreasen NC (1982) Negative symptoms in schizophrenia. Definition and reliability. Arch Gen Psychiatry 39:784–788CrossRefPubMed Andreasen NC (1982) Negative symptoms in schizophrenia. Definition and reliability. Arch Gen Psychiatry 39:784–788CrossRefPubMed
4.
go back to reference Arneric SP, Holladay M, Williams M (2007) Neuronal nicotinic receptors: a perspective on two decades of drug discovery research. Biochem Pharmacol 74:1092–1101CrossRefPubMed Arneric SP, Holladay M, Williams M (2007) Neuronal nicotinic receptors: a perspective on two decades of drug discovery research. Biochem Pharmacol 74:1092–1101CrossRefPubMed
5.
go back to reference Arnulf I (2012) Rem sleep behavior disorder: motor manifestations and pathophysiology. Mov Disord Off J Mov Disord Soc 27:677–689CrossRef Arnulf I (2012) Rem sleep behavior disorder: motor manifestations and pathophysiology. Mov Disord Off J Mov Disord Soc 27:677–689CrossRef
6.
go back to reference Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571CrossRefPubMed Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571CrossRefPubMed
7.
go back to reference Berk M, Dodd S, Kauer-Sant’anna M, Malhi GS, Bourin M, Kapczinski F, Norman T (2007) Dopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder. Acta Psychiatr Scand Suppl:41–49 Berk M, Dodd S, Kauer-Sant’anna M, Malhi GS, Bourin M, Kapczinski F, Norman T (2007) Dopamine dysregulation syndrome: implications for a dopamine hypothesis of bipolar disorder. Acta Psychiatr Scand Suppl:41–49
8.
go back to reference Dalack GW, Healy DJ, Meador-Woodruff JH (1998) Nicotine dependence in schizophrenia: clinical phenomena and laboratory findings. Am J Psychiatry 155:1490–1501CrossRefPubMed Dalack GW, Healy DJ, Meador-Woodruff JH (1998) Nicotine dependence in schizophrenia: clinical phenomena and laboratory findings. Am J Psychiatry 155:1490–1501CrossRefPubMed
9.
10.
go back to reference Dutra SJ, Stoeckel LE, Carlini SV, Pizzagalli DA, Evins AE (2012) Varenicline as a smoking cessation aid in schizophrenia: effects on smoking behavior and reward sensitivity. Psychopharmacology 219:25–34CrossRefPubMedCentralPubMed Dutra SJ, Stoeckel LE, Carlini SV, Pizzagalli DA, Evins AE (2012) Varenicline as a smoking cessation aid in schizophrenia: effects on smoking behavior and reward sensitivity. Psychopharmacology 219:25–34CrossRefPubMedCentralPubMed
11.
go back to reference Evins AE, Cather C, Pratt SA, Pachas GN, Hoeppner SS, Goff DC, Achtyes ED, Ayer D, Schoenfeld DA (2014) Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial. J Am Med Assoc 311:145–154CrossRef Evins AE, Cather C, Pratt SA, Pachas GN, Hoeppner SS, Goff DC, Achtyes ED, Ayer D, Schoenfeld DA (2014) Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial. J Am Med Assoc 311:145–154CrossRef
12.
go back to reference Fatemi SH, Yousefi MK, Kneeland RE, Liesch SB, Folsom TD, Thuras PD (2013) Antismoking and potential antipsychotic effects of varenicline in subjects with schizophrenia or schizoaffective disorder: a double-blind placebo and bupropion-controlled study. Schizophr Res 146:376–378CrossRefPubMed Fatemi SH, Yousefi MK, Kneeland RE, Liesch SB, Folsom TD, Thuras PD (2013) Antismoking and potential antipsychotic effects of varenicline in subjects with schizophrenia or schizoaffective disorder: a double-blind placebo and bupropion-controlled study. Schizophr Res 146:376–378CrossRefPubMed
13.
14.
go back to reference Goff DC, Henderson DC, Amico E (1992) Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. Am J Psychiatry 149:1189–1194CrossRefPubMed Goff DC, Henderson DC, Amico E (1992) Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. Am J Psychiatry 149:1189–1194CrossRefPubMed
15.
go back to reference Gupta A, Bastiampillai T, Adams M, Nelson A, Nance M (2012) Varenicline induced psychosis in schizophrenia. Aust N Zeal J Psychiatry 46:1009CrossRef Gupta A, Bastiampillai T, Adams M, Nelson A, Nance M (2012) Varenicline induced psychosis in schizophrenia. Aust N Zeal J Psychiatry 46:1009CrossRef
17.
go back to reference Hashimoto K, Ishima T, Fujita Y, Matsuo M, Kobashi T, Takahagi M, Tsukada H, Iyo M (2008) Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the novel selective alpha7 nicotinic receptor agonist ssr180711. Biol Psychiatry 63:92–97CrossRefPubMed Hashimoto K, Ishima T, Fujita Y, Matsuo M, Kobashi T, Takahagi M, Tsukada H, Iyo M (2008) Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the novel selective alpha7 nicotinic receptor agonist ssr180711. Biol Psychiatry 63:92–97CrossRefPubMed
19.
go back to reference Ho KK, Pinsky JL, Kannel WB, Levy D (1993) The epidemiology of heart failure: the framingham study. J Am Coll Cardiol 22:6A–13ACrossRefPubMed Ho KK, Pinsky JL, Kannel WB, Levy D (1993) The epidemiology of heart failure: the framingham study. J Am Coll Cardiol 22:6A–13ACrossRefPubMed
20.
go back to reference Hong LE, Thaker GK, McMahon RP, Summerfelt A, Rachbeisel J, Fuller RL, Wonodi I, Buchanan RW, Myers C, Heishman SJ, Yang J, Nye A (2011) Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 68:1195–1206CrossRefPubMedCentralPubMed Hong LE, Thaker GK, McMahon RP, Summerfelt A, Rachbeisel J, Fuller RL, Wonodi I, Buchanan RW, Myers C, Heishman SJ, Yang J, Nye A (2011) Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 68:1195–1206CrossRefPubMedCentralPubMed
21.
go back to reference Hughes JR, Hatsukami DK, Mitchell JE, Dahlgren LA (1986) Prevalence of smoking among psychiatric outpatients. Am J Psychiatry 143:993–997CrossRefPubMed Hughes JR, Hatsukami DK, Mitchell JE, Dahlgren LA (1986) Prevalence of smoking among psychiatric outpatients. Am J Psychiatry 143:993–997CrossRefPubMed
22.
go back to reference Ismail Z, Syms J, Blumberger D, George TP (2010) Varenicline induced polydipsia and hyponatremia in a patient with schizophrenia. Schizophr Res 119:268CrossRefPubMed Ismail Z, Syms J, Blumberger D, George TP (2010) Varenicline induced polydipsia and hyponatremia in a patient with schizophrenia. Schizophr Res 119:268CrossRefPubMed
23.
go back to reference Kaalund SS, Newburn EN, Ye T, Tao R, Li C, Deep-Soboslay A, Herman MM, Hyde TM, Weinberger DR, Lipska BK, Kleinman JE (2013) Contrasting changes in drd1 and drd2 splice variant expression in schizophrenia and affective disorders, and associations with snps in postmortem brain. Mol Psychiatry Kaalund SS, Newburn EN, Ye T, Tao R, Li C, Deep-Soboslay A, Herman MM, Hyde TM, Weinberger DR, Lipska BK, Kleinman JE (2013) Contrasting changes in drd1 and drd2 splice variant expression in schizophrenia and affective disorders, and associations with snps in postmortem brain. Mol Psychiatry
24.
go back to reference Lieberman JA, Dunbar G, Segreti AC, Girgis RR, Seoane F, Beaver JS, Duan N, Hosford DA (2013) A randomized exploratory trial of an alpha-7 nicotinic receptor agonist (tc-5619) for cognitive enhancement in schizophrenia. Neuropsychopharmacol Off Publ Am College Neuropsychopharmacol 38:968–975CrossRef Lieberman JA, Dunbar G, Segreti AC, Girgis RR, Seoane F, Beaver JS, Duan N, Hosford DA (2013) A randomized exploratory trial of an alpha-7 nicotinic receptor agonist (tc-5619) for cognitive enhancement in schizophrenia. Neuropsychopharmacol Off Publ Am College Neuropsychopharmacol 38:968–975CrossRef
25.
go back to reference Lising-Enriquez K, George TP (2009) Treatment of comorbid tobacco use in people with serious mental illness. J Psychiatry Neurosci 34:E1–E2PubMedCentralPubMed Lising-Enriquez K, George TP (2009) Treatment of comorbid tobacco use in people with serious mental illness. J Psychiatry Neurosci 34:E1–E2PubMedCentralPubMed
26.
go back to reference Liu ME, Tsai SJ, Jeang SY, Peng SL, Wu SL, Chen MC, Tsai YL, Yang ST (2011) Varenicline prevents affective and cognitive exacerbation during smoking abstinence in male patients with schizophrenia. Psychiatry Res 190:79–84CrossRefPubMed Liu ME, Tsai SJ, Jeang SY, Peng SL, Wu SL, Chen MC, Tsai YL, Yang ST (2011) Varenicline prevents affective and cognitive exacerbation during smoking abstinence in male patients with schizophrenia. Psychiatry Res 190:79–84CrossRefPubMed
27.
go back to reference Meszaros ZS, Abdul-Malak Y, Dimmock JA, Wang D, Ajagbe TO, Batki SL (2013) Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia: a randomized, placebo-controlled pilot trial. J Clin Psychopharmacol 33:243–247CrossRefPubMed Meszaros ZS, Abdul-Malak Y, Dimmock JA, Wang D, Ajagbe TO, Batki SL (2013) Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia: a randomized, placebo-controlled pilot trial. J Clin Psychopharmacol 33:243–247CrossRefPubMed
28.
go back to reference Mihalak KB, Carroll FI, Luetje CW (2006) Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol 70:801–805CrossRefPubMed Mihalak KB, Carroll FI, Luetje CW (2006) Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol 70:801–805CrossRefPubMed
29.
go back to reference Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the prisma statement. BMJ 339:b2535 Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the prisma statement. BMJ 339:b2535
30.
go back to reference Montoya ID, Vocci F (2007) Medications development for the treatment of nicotine dependence in individuals with schizophrenia. J Dual Diagn 3:113–150CrossRefPubMedCentralPubMed Montoya ID, Vocci F (2007) Medications development for the treatment of nicotine dependence in individuals with schizophrenia. J Dual Diagn 3:113–150CrossRefPubMedCentralPubMed
31.
go back to reference Ortiz G, Schacht L, Lane GM (2013) Smoking cessation care in state-operated or state-supported psychiatric hospitals: from policy to practice. Psychiatric Serv 64:666–671CrossRef Ortiz G, Schacht L, Lane GM (2013) Smoking cessation care in state-operated or state-supported psychiatric hospitals: from policy to practice. Psychiatric Serv 64:666–671CrossRef
32.
go back to reference Overall JE, Gorham DR (1962) The brief psychiatric rating scale. Psychol Rep 10:799–812CrossRef Overall JE, Gorham DR (1962) The brief psychiatric rating scale. Psychol Rep 10:799–812CrossRef
33.
go back to reference Patkar AA, Gopalakrishnan R, Lundy A, Leone FT, Certa KM, Weinstein SP (2002) Relationship between tobacco smoking and positive and negative symptoms in schizophrenia. J Nerv Ment Dis 190:604–610CrossRefPubMed Patkar AA, Gopalakrishnan R, Lundy A, Leone FT, Certa KM, Weinstein SP (2002) Relationship between tobacco smoking and positive and negative symptoms in schizophrenia. J Nerv Ment Dis 190:604–610CrossRefPubMed
34.
go back to reference Shim JC, Jung DU, Jung SS, Seo YS, Cho DM, Lee JH, Lee SW, Kong BG, Kang JW, Oh MK, Kim SD, McMahon RP, Kelly DL (2012) Adjunctive varenicline treatment with antipsychotic medications for cognitive impairments in people with schizophrenia: a randomized double-blind placebo-controlled trial. Neuropsychopharmacol Off Publ Am College Neuropsychopharmacol 37:660–668CrossRef Shim JC, Jung DU, Jung SS, Seo YS, Cho DM, Lee JH, Lee SW, Kong BG, Kang JW, Oh MK, Kim SD, McMahon RP, Kelly DL (2012) Adjunctive varenicline treatment with antipsychotic medications for cognitive impairments in people with schizophrenia: a randomized double-blind placebo-controlled trial. Neuropsychopharmacol Off Publ Am College Neuropsychopharmacol 37:660–668CrossRef
35.
go back to reference Smith RC, Lindenmayer JP, Davis JM, Cornwell J, Noth K, Gupta S, Sershen H, Lajtha A (2009) Cognitive and antismoking effects of varenicline in patients with schizophrenia or schizoaffective disorder. Schizophr Res 110:149–155CrossRefPubMed Smith RC, Lindenmayer JP, Davis JM, Cornwell J, Noth K, Gupta S, Sershen H, Lajtha A (2009) Cognitive and antismoking effects of varenicline in patients with schizophrenia or schizoaffective disorder. Schizophr Res 110:149–155CrossRefPubMed
36.
go back to reference Smith RC, Zhubi A, Maloku E, Sershen H, Lajtha A, Davis JM, Costa E, Guidotti A (2010) Varenicline treatment decreases dnmt1 mrna expression in lymphocytes of schizophrenic patients who are cigarette smokers. Schizophr Res 119:269–270CrossRefPubMed Smith RC, Zhubi A, Maloku E, Sershen H, Lajtha A, Davis JM, Costa E, Guidotti A (2010) Varenicline treatment decreases dnmt1 mrna expression in lymphocytes of schizophrenic patients who are cigarette smokers. Schizophr Res 119:269–270CrossRefPubMed
37.
go back to reference Trbovic SM (2010) Schizophrenia as a possible dysfunction of the suprachiasmatic nucleus. Med Hypotheses 74:127–131CrossRefPubMed Trbovic SM (2010) Schizophrenia as a possible dysfunction of the suprachiasmatic nucleus. Med Hypotheses 74:127–131CrossRefPubMed
38.
go back to reference Tsoi DT, Porwal M, Webster AC (2013) Interventions for smoking cessation and reduction in individuals with schizophrenia. Cochrane Database Syst Rev 2:CD007253 Tsoi DT, Porwal M, Webster AC (2013) Interventions for smoking cessation and reduction in individuals with schizophrenia. Cochrane Database Syst Rev 2:CD007253
39.
go back to reference Umbricht D, Keefe RS, Murray S, Lowe DA, Porter R, Garibaldi G, Santarelli L (2014) A randomized, placebo-controlled study investigating the nicotinic alpha7 agonist, rg3487, for cognitive deficits in schizophrenia. Neuropsychopharmacol Off Publ Am College Neuropsychopharmacol Umbricht D, Keefe RS, Murray S, Lowe DA, Porter R, Garibaldi G, Santarelli L (2014) A randomized, placebo-controlled study investigating the nicotinic alpha7 agonist, rg3487, for cognitive deficits in schizophrenia. Neuropsychopharmacol Off Publ Am College Neuropsychopharmacol
40.
go back to reference Vineis P, Airoldi L, Veglia F, Olgiati L, Pastorelli R, Autrup H, Dunning A, Garte S, Gormally E, Hainaut P, Malaveille C, Matullo G, Peluso M, Overvad K, Tjonneland A, Clavel-Chapelon F, Boeing H, Krogh V, Palli D, Panico S, Tumino R, Bueno-De-Mesquita B, Peeters P, Berglund G, Hallmans G, Saracci R, Riboli E (2005) Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the epic prospective study. BMJ 330:277CrossRefPubMedCentralPubMed Vineis P, Airoldi L, Veglia F, Olgiati L, Pastorelli R, Autrup H, Dunning A, Garte S, Gormally E, Hainaut P, Malaveille C, Matullo G, Peluso M, Overvad K, Tjonneland A, Clavel-Chapelon F, Boeing H, Krogh V, Palli D, Panico S, Tumino R, Bueno-De-Mesquita B, Peeters P, Berglund G, Hallmans G, Saracci R, Riboli E (2005) Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the epic prospective study. BMJ 330:277CrossRefPubMedCentralPubMed
41.
go back to reference Weiner E, Buchholz A, Coffay A, Liu F, McMahon RP, Buchanan RW, Kelly DL (2011) Varenicline for smoking cessation in people with schizophrenia: a double blind randomized pilot study. Schizophr Res 129:94–95CrossRefPubMedCentralPubMed Weiner E, Buchholz A, Coffay A, Liu F, McMahon RP, Buchanan RW, Kelly DL (2011) Varenicline for smoking cessation in people with schizophrenia: a double blind randomized pilot study. Schizophr Res 129:94–95CrossRefPubMedCentralPubMed
42.
go back to reference Williams JM, Anthenelli RM, Morris CD, Treadow J, Thompson JR, Yunis C, George TP (2012) A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder. J Clin Psychiatry 73:654–660CrossRefPubMed Williams JM, Anthenelli RM, Morris CD, Treadow J, Thompson JR, Yunis C, George TP (2012) A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder. J Clin Psychiatry 73:654–660CrossRefPubMed
43.
go back to reference Young JW, Geyer MA (2013) Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia. Biochem Pharmacol 86:1122–1132CrossRefPubMedCentralPubMed Young JW, Geyer MA (2013) Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia. Biochem Pharmacol 86:1122–1132CrossRefPubMedCentralPubMed
44.
go back to reference Yousefi MK, Folsom TD, Fatemi SH (2011) A review of varenicline’s efficacy and tolerability in smoking cessation studies in subjects with schizophrenia. J Addict Res Ther S4 Yousefi MK, Folsom TD, Fatemi SH (2011) A review of varenicline’s efficacy and tolerability in smoking cessation studies in subjects with schizophrenia. J Addict Res Ther S4
45.
go back to reference Ziedonis DM, George TP (1997) Schizophrenia and nicotine use: report of a pilot smoking cessation program and review of neurobiological and clinical issues. Schizophr Bull 23:247–254CrossRefPubMed Ziedonis DM, George TP (1997) Schizophrenia and nicotine use: report of a pilot smoking cessation program and review of neurobiological and clinical issues. Schizophr Bull 23:247–254CrossRefPubMed
Metadata
Title
Varenicline for smoking cessation in people with schizophrenia: systematic review and meta-analysis
Authors
Taro Kishi
Nakao Iwata
Publication date
01-04-2015
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Psychiatry and Clinical Neuroscience / Issue 3/2015
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI
https://doi.org/10.1007/s00406-014-0551-3

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