Risk of neuropsychiatric adverse events associated with varenicline: Systematic review and meta-analysis

BMJ (Online)

Volumn 350, Issue , 2015, Pages

  Thomas, Kyla H ^a   Martin, Richard M ^a   Knipe, Duleeka W ^a   Higgins, Julian P T ^a   Gunnell, David ^a  

^a UNIVERSITY OF BRISTOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PLACEBO; VARENICLINE; BENZAZEPINE DERIVATIVE; NICOTINE GUM; QUINOXALINE DERIVATIVE;

ABNORMAL DREAMING; AGE DISTRIBUTION; AGGRESSION; ANXIETY; CAUCASIAN; DEPRESSION; DRUG EFFICACY; DRUG RESPONSE; ETHNICITY; GENDER; HUMAN; INSOMNIA; IRRITABILITY; MENTAL DISEASE; META ANALYSIS; NAUSEA AND VOMITING; NEUROPSYCHIATRY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK ASSESSMENT; RISK FACTOR; RISK REDUCTION; SLEEP DISORDER; SMOKING; SOMNOLENCE; SUICIDAL IDEATION; SUICIDE ATTEMPT; SYSTEMATIC REVIEW; TREATMENT DURATION; CHEMICALLY INDUCED; DRUG EFFECTS; STATISTICS AND NUMERICAL DATA; SUICIDE;

AGGRESSION; BENZAZEPINES; DEPRESSION; HUMANS; MENTAL DISORDERS; QUINOXALINES; RISK FACTORS; SLEEP WAKE DISORDERS; SUICIDE; SUICIDE, ATTEMPTED; TOBACCO USE CESSATION PRODUCTS; VARENICLINE;

EID: 84926148511     PISSN: 09598146     EISSN: 17561833     Source Type: Journal    
DOI: 10.1136/bmj.h1109     Document Type: Review

References (72)

1. Jha P, Peto R. Global effects of smoking, of quitting, and of taxing tobacco. N Engl J Med 2014;370:60-8.
2. Allender S, Balakrishnan R, Scarborough P, Webster P, Rayner M. The burden of smoking-related ill health in the UK. Tob Control 2009;18:262-67.
3. 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.
4. Medicines and Healthcare Products Regulatory Agency. Varenicline: adverse psychiatric reactions, including depression. Drug Safety Update 2008;2:2-3.
5. US Food and Drug Administration. Information for healthcare professionals: varenicline (marketed as Chantix) and bupropion (marketed as Zyban, Wellbutrin and generics). FDA Drug Safety Newsletter, 2009.
6. Gunnell D, Irvine D, Wise L, Davies C, Martin RM. Varenicline and suicidal behaviour: a cohort study based on data from the General Practice Research Database. BMJ 2009;339;b3805.
7. Meyer TE, Taylor LG, Xie S, Graham DJ, Mosholder AD, Williams JR, et al. Neuropsychiatric events in varenicline and nicotine replacement patch users in the Military Health System. Addiction 2013;108:203-10.
8. Thomas KH, Martin RM, Davies N, Metcalfe C, Windmeijer F, Gunnell D. Smoking cessation treatment and the risk of depression, suicide and self-harm in the Clinical Practice Research Datalink: prospective cohort study BMJ 2013;347:f5704.
9. Gibbons RD, Mann JJ. Varenicline, smoking cessation, and neuropsychiatric adverse events. Am J Psychiatry 2013;170:1460-7.
10. Walker AM. Confounding by indication. Epidemiology 1996;7:335-6.
11. Miller M, Hemenway D, Bell NS, Yore MM, Amoroso PJ. Cigarette smoking and suicide: a prospective study of 300,000 male active-duty Army soldiers. Am J Epidemiol 2000;151:1060-3.
12. Miller M, Hemenway D, Rimm E. Cigarettes and suicide: a prospective study of 50,000 men. Am J Public Health 2000;90:768-73.
13. Etter JF, Burri M, Stapleton J. The impact of pharmaceutical company funding on results of randomized trials of nicotine replacement therapy for smoking cessation: a meta-analysis. Addiction 2007;102:815-22.
14. Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2012;4:CD006103.
15. Higgins JPT, Altman DG. Assessing risk of bias in included studies. Cochrane handbook for systematic reviews of interventions. John Wiley, 2008:187-241.
16. Harris R, Bradburn M, Deeks J, Harbord R, Altman D, Sterne J. metan: fixed- and random-effects meta-analysis. Stata J 2008;8:3-28.
17. Bradburn MJ, Deeks JJ, Berlin JA, Russell Localio A. Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events. Stat Med 2007;26:53-77.
18. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.
19. Higgins JPT, Deeks JJ, Altman DG. Special topics in statistics. Cochrane handbook for systematic reviews of interventions. John Wiley, 2008:481-529.
20. Sterne JAC, Harbord RM. Funnel plots in meta-analysis. Stata J 2004;4:127-41.
21. Harbord RM, Harris RJ, Sterne JAC. Updated tests for small-study effects in meta-analyses. Stata J 2009;9:197-210.
22. Anthenelli RM, Morris C, Ramey TS, Dubrava SJ, Tsilkos K, Russ C, et al. Effects of varenicline on smoking cessation in adults with stably treated current or past major depression: a randomized trial. Ann Intern Med 2013;159:390-400.
23. Bolliger CT, Issa JS, Posadas-Valay R, Safwat T, Abreu P, Correia EA, et al. Effects of varenicline in adult smokers: a multinational, 24-week, randomized, double-blind, placebo-controlled study. Clin Ther 2011;33:465-77.
24. Brandon TH, Drobes DJ, Unrod M, Heckman BW, Oliver JA, Roetzheim RC, et al. Varenicline effects on craving, cue reactivity, and smoking reward. Psychopharmacology (Berl) 2011;218:391-403.
25. Burstein AH, Fullerton T, Clark DJ, Faessel HM. Pharmacokinetics, safety, and tolerability after single and multiple oral doses of varenicline in elderly smokers. J Clin Pharmacol 2006;46:1234-40.
26. Cinciripini PM, Robinson JD, Karam-Hage M, Minnix JA, Lam C, Versace F, 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;70:522-33.
27. Ebbert JO, Croghan IT, Severson HH, Schroeder DR, Hays JT. A pilot study of the efficacy of varenicline for the treatment of smokeless tobacco users in Midwestern United States. Nicotine Tob Res 2011;13:820-6.
28. Evins AE, Cather C, Pratt SA, Pachas GN, Hoeppner SS, Goff DC, et al. Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial. JAMA 2014;311:145-54.
29. Faessel H, Ravva P, Williams K. Pharmacokinetics, safety, and tolerability of varenicline in healthy adolescent smokers: a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther 2009;31:177-89.
30. Fagerstrom K, Gilljam H, Metcalfe M, Tonstad S, Messig M. Stopping smokeless tobacco with varenicline: randomised double blind placebo controlled trial. BMJ 2010;341:c6549.
31. Fatemi SH, Yousefi MK, Kneeland RE, Liesch SB, Folsom TD, Thuras PD. Antismoking and potential antipsychotic effects of varenicline in subjects with schizophrenia or schizoaffective disorder: a double-blind placebo and bupropion-controlled study. Schizophr Res 2013;146:376-8.
32. Garza D, Murphy M, Tseng LJ, Riordan HJ, Chatterjee A. A double-blind randomized placebo-controlled pilot study of neuropsychiatric adverse events in abstinent smokers treated with varenicline or placebo. Biol Psychiatry 2011;69:1075-82.
33. Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, 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;296:47-55.
34. Hughes JR, Rennard SI, Fingar JR, Talbot SK, Callas PW, Fagerstrom KO. Efficacy of varenicline to prompt quit attempts in smokers not currently trying to quit: a randomized placebo-controlled trial. Nicotine Tob Res 2011;13:955-64.
35. Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, et al. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 2006;296:56-63.
36. Litten RZ, Ryan ML, Fertig JB, Falk DE, Johnson B, Dunn KE, et al. A double-blind, placebo-controlled trial assessing the efficacy of varenicline tartrate for alcohol dependence. J Addict Med 2013;7:277-86.
37. McClure EA, Vandrey RG, Johnson MW, Stitzer ML. Effects of varenicline on abstinence and smoking reward following a programmed lapse. Nicotine Tob Res 2013;15:139-48.
38. McKee SA, Harrison EL, O'Malley SS, Krishnan-Sarin S, Shi J, Tetrault JM, et al. Varenicline reduces alcohol self-administration in heavy-drinking smokers. Biol Psychiatry 2009;66:185-90.
39. Meszaros ZS, Abdul-Malak Y, Dimmock JA, Wang D, Ajagbe TO, Batki SL. Varenicline treatment of concurrent alcohol and nicotine dependence in schizophrenia: a randomized, placebo-controlled pilot trial. J Clin Psychopharmacol 2013;33:243-7.
40. Mitchell JM, Teague CH, Kayser AS, Bartlett SE, Fields HL. Varenicline decreases alcohol consumption in heavy-drinking smokers. Psychopharmacology (Berl) 2012;223:299-306.
41. Nakamura M, Oshima A, Fujimoto Y, Maruyama N, Ishibashi T, Reeves KR. Efficacy and tolerability of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers. Clin Ther 2007;29:1040-56.
42. Niaura R, Hays JT, Jorenby DE, Leone FT, Pappas JE, Reeves KR, et al. The efficacy and safety of varenicline for smoking cessation using a flexible dosing strategy in adult smokers: a randomized controlled trial. Curr Med Res Opin 2008;24:1931-41.
43. Nides M, Oncken C, Gonzales D, Rennard S, Watsky EJ, Anziano R, et al. Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med 2006;166:1561-8.
44. Oncken C, Gonzales D, Nides M, Rennard S, Watsky E, Billing CB, et al. Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Arch Intern Med 2006;166:1571-7.
45. Plebani JG, Lynch KG, Yu Q, Pettinati HM, O'Brien CP, Kampman KM. Results of an initial clinical trial of varenicline for the treatment of cocaine dependence. Drug Alcohol Depend 2012;121:163-6.
46. Plebani JG, Lynch KG, Rennert L, Pettinati HM, O'Brien CP, Kampman KM. Results from a pilot clinical trial of varenicline for the treatment of alcohol dependence. Drug Alcohol Depend 2013;133:754-8.
47. Poling J, Rounsaville B, Gonsai K, Severino K, Sofuoglu M. The safety and efficacy of varenicline in cocaine using smokers maintained on methadone: a pilot study. Am J Addict 2010;19:401-8.
48. Rennard S, Hughes J, Cinciripini PM, Kralikova E, Raupach T, Arteaga C, et al. A randomized placebo-controlled trial of varenicline for smoking cessation allowing flexible quit dates. Nicotine Tob Res 2012;14:343-50.
49. Rigotti NA, Pipe AL, Benowitz NL, Arteaga C, Garza D, Tonstad S. Efficacy and safety of varenicline for smoking cessation in patients with cardiovascular disease: a randomized trial. Circulation 2010;121:221-9.
50. Shim JC, Jung DU, Jung SS, Seo YS, Cho DM, Lee JH, et al. Adjunctive varenicline treatment with antipsychotic medications for cognitive impairments in people with schizophrenia: a randomized double-blind placebo-controlled trial. Neuropsychopharmacology 2012;37:660-8.
51. Stein MD, Caviness CM, Kurth ME, Audet D, Olson J, Anderson BJ. Varenicline for smoking cessation among methadone-maintained smokers: a randomized clinical trial. Drug Alcohol Depend 2013;133:486-93.
52. Steinberg MB, Randall J, Greenhaus S, Schmelzer AC, Richardson DL, Carson JL. Tobacco dependence treatment for hospitalized smokers: a randomized, controlled, pilot trial using varenicline. Addic Behav 2011;36:1127-32.
53. Tashkin DP, Rennard S, Hays JT, Ma W, Lawrence D, Lee TC. Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial. Chest 2011;139:591-9.
54. Tonnesen P, Mikkelsen K. Varenicline to stop long-term nicotine replacement use: a double-blind, randomized, placebo-controlled trial. Nicotine Tob Res 2013;15:419-27.
55. Tonstad S, Tonnesen P, Hajek P, Williams KE, Billing CB, Reeves KR, et al. Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial. JAMA 2006;296:64-71.
56. Tsai ST, Cho HJ, Cheng HS, Kim CH, Hsueh KC, Billing CB, Jr., et al. A randomized, placebo-controlled trial of varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers. Clin Ther 2007;29:1027-39.
57. Wang C, Xiao D, Chan KPW, Pothirat C, Garza D, Davies S. Varenicline for smoking cessation: A placebo-controlled, randomized study. Respirology 2009;14:384-92.
58. Weiner E, Buchholz A, Coffay A, Liu F, McMahon RP, Buchanan RW, et al. Varenicline for smoking cessation in people with schizophrenia: a double blind randomized pilot study. Schizophr Res 2011;129:94-5.
59. Williams K, Reeves K, Billing C, Pennington A, Gong J. A double-blind study evaluating the long-term safety of varenicline for smoking cessation. Curr Med Res Opin 2007;23:793-801.
60. Williams JM, Anthenelli RM, Morris CD, Treadow J, Thompson JR, Yunis C, et al. 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 2012;73:654-60.
61. Wong J, Abrishami A, Yang Y, Zaki A, Friedman Z, Selby P, et al. A perioperative smoking cessation intervention with varenicline: a double-blind, randomized, placebo-controlled trial. Anesthesiology 2012;117:755-64.
62. Zesiewicz TA, Greenstein PE, Sullivan KL, Wecker L, Miller A, Jahan I, et al. A randomized trial of varenicline (Chantix) for the treatment of spinocerebellar ataxia type 3. Neurology 2012;78:545-50.
63. Zhao Q, Schwam E, Fullerton T, O'Gorman M, Burstein AH. Pharmacokinetics, safety, and tolerability following multiple oral doses of varenicline under various titration schedules in elderly nonsmokers. J Clin Pharmacol 2011;51:492-501.
64. Chengappa KN, Perkins KA, Brar JS, Schlicht PJ, Turkin SR, Hetrick ML, et al. Varenicline for smoking cessation in bipolar disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2014;75:765-72.
65. Gonzales D, Hajek P, Pliamm L, Nackaerts K, Tseng LJ, McRae TD, et al. Retreatment with varenicline for smoking cessation in smokers who have previously taken varenicline: a randomized, placebo-controlled trial. Clin Pharmacol Ther 2014;96:390-6.
66. Kishi T, Iwata N. Varenicline for smoking cessation in people with schizophrenia: systematic review and meta-analysis. Eur Arch Psychiatry Clin Neurosci 2014 Oct 5 [Epub ahead of print].
67. Hong LE, Thaker GK, McMahon RP, Summerfelt A, Rachbeisel J, Fuller RL, et al. Effects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 2011;68:1195-206.
68. Huang Y, Li W, Yang L, Jiang Y, Wu Y. Long-term efficacy and safety of varenicline for smoking cessation: a systematic review and meta-analysis of randomized controlled trials. J Public Health 2012;20:355-65.
69. 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;183:1359-66.
70. Prochaska JJ, Hilton JF. Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis. BMJ 2012;344:e2856.
71. Mocking RJ, Patrick Pflanz C, Pringle A, Parsons E, McTavish SF, Cowen PJ, et al. Effects of short-term varenicline administration on emotional and cognitive processing in healthy, non-smoking adults: a randomized, double-blind, study. Neuropsychopharmacology 2013;38:476-84.
72. Taylor G, McNeill A, Girling A, Farley A, Lindson-Hawley N, Aveyard P. Change in mental health after smoking cessation: systematic review and meta-analysis. BMJ 2014;348:g1151.