A Study of Varenicline for Prevention of Relapse to Smoking in Patients With Schizophrenia or Bipolar Disorder

Summary

Varenicline (Chantix) is a smoking cessation treatment that was approved in 2006 by the FDA for treatment of nicotine dependence and may be particularly beneficial in smokers with schizophrenia or bipolar disorder. Early experience with varenicline indicates that it will be effective for smoking cessation in schizophrenia and in addition, has the potential to be therapeutic for cognitive dysfunction in this population. In addition, more data is needed to evaluate the safety, tolerability and effectiveness of Varenicline in people with bipolar disorder. To assess this possibility, we will evaluate the safety and efficacy of 12 months of varenicline in schizophrenia or bipolar disorder patients who are able to quit smoking in the short term with this treatment. To do so, we will enroll 324 smokers with schizophrenia or bipolar disorder from 6 mental health clinics in Massachusetts, New Hampshire, Michigan and Minnesota into an open, 12-week smoking cessation program that includes varenicline added to weekly group cognitive behavioral therapy (CBT). Those who achieve at least 2 weeks of continuous abstinence during the last 2 weeks of the open intervention will be randomized to the relapse prevention phase: a 40-week, double blind, placebo-controlled trial of varenicline at the dose used to quit smoking added to a tapering CBT schedule. Participants will then discontinue study medications and behavioral treatment and enter a 3-month follow up phase.

Timeline

Start

2008-02

Primary completion

2013-05

Completion

2013-05

Publications

• Background From the Centers for Disease Control and Prevention. Annual smoking attributable mortality, years of potential life lost and economic costs--United States, 1995-1999. JAMA. 2002 May 8;287(18):2355-6. No abstract available.
• Background Addington J, el-Guebaly N, Addington D, Hodgins D. Readiness to stop smoking in schizophrenia. Can J Psychiatry. 1997 Feb;42(1):49-52. doi: 10.1177/070674379704200107.
• Background Adler LE, Olincy A, Waldo M, Harris JG, Griffith J, Stevens K, Flach K, Nagamoto H, Bickford P, Leonard S, Freedman R. Schizophrenia, sensory gating, and nicotinic receptors. Schizophr Bull. 1998;24(2):189-202. doi: 10.1093/oxfordjournals.schbul.a033320.
• Background Barr, R.S.; Culhane, M.A.; Pizzagalli, D.; Goff, D.C.; and Evins, A.E. A double blind placebo controlled trial of the effects of transdermal nicotine on reward responsivity in non-smokers with schizophrenia. NIMH New Clinical Drug Evaluation Unit. Boca Raton, FL, 2006
• Background Breese CR, Lee MJ, Adams CE, Sullivan B, Logel J, Gillen KM, Marks MJ, Collins AC, Leonard S. Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia. Neuropsychopharmacology. 2000 Oct;23(4):351-64. doi: 10.1016/S0893-133X(00)00121-4.
• Background Carroll KM, Nich C, Sifry RL, Nuro KF, Frankforter TL, Ball SA, Fenton L, Rounsaville BJ. A general system for evaluating therapist adherence and competence in psychotherapy research in the addictions. Drug Alcohol Depend. 2000 Jan 1;57(3):225-38. doi: 10.1016/s0376-8716(99)00049-6.
• Background 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 Mar;152(3):453-5. doi: 10.1176/ajp.152.3.453.
• Background 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 Jul 1;56(1-2):47-54. doi: 10.1016/s0920-9964(01)00217-1.
• Background Evins AE, Cather C, Rigotti NA, Freudenreich O, Henderson DC, Olm-Shipman CM, Goff DC. Two-year follow-up of a smoking cessation trial in patients with schizophrenia: increased rates of smoking cessation and reduction. J Clin Psychiatry. 2004 Mar;65(3):307-11; quiz 452-3. doi: 10.4088/jcp.v65n0304.
• Background Evins AE, Cather C, Deckersbach T, Freudenreich O, Culhane MA, Olm-Shipman CM, Henderson DC, Schoenfeld DA, Goff DC, Rigotti NA. A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia. J Clin Psychopharmacol. 2005 Jun;25(3):218-25. doi: 10.1097/01.jcp.0000162802.54076.18.
• Background Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J, Williams KE, Reeves KR; Varenicline Phase 3 Study Group. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006 Jul 5;296(1):47-55. doi: 10.1001/jama.296.1.47.
• Background Hughes JR, Hatsukami DK, Mitchell JE, Dahlgren LA. Prevalence of smoking among psychiatric outpatients. Am J Psychiatry. 1986 Aug;143(8):993-7. doi: 10.1176/ajp.143.8.993.
• Background Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR; Varenicline Phase 3 Study Group. 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 Jul 5;296(1):56-63. doi: 10.1001/jama.296.1.56.
• Background Mihalak KB, Carroll FI, Luetje CW. Varenicline is a partial agonist at alpha4beta2 and a full agonist at alpha7 neuronal nicotinic receptors. Mol Pharmacol. 2006 Sep;70(3):801-5. doi: 10.1124/mol.106.025130. Epub 2006 Jun 9.
• Background Diaz FJ, James D, Botts S, Maw L, Susce MT, de Leon J. Tobacco smoking behaviors in bipolar disorder: a comparison of the general population, schizophrenia, and major depression. Bipolar Disord. 2009 Mar;11(2):154-65. doi: 10.1111/j.1399-5618.2009.00664.x.
• Cather C, Hoeppner S, Pachas G, Pratt S, Achtyes E, Cieslak KM, Evins AE. Improved Depressive Symptoms in Adults with Schizophrenia During a Smoking Cessation Attempt with Varenicline and Behavioral Therapy. J Dual Diagn. 2017 Jul-Sep;13(3):168-178. doi: 10.1080/15504263.2017.1319585. Epub 2017 Apr 17.
• Thorndike AN, Achtyes ED, Cather C, Pratt S, Pachas GN, Hoeppner SS, Evins AE. Weight gain and 10-year cardiovascular risk with sustained tobacco abstinence in smokers with serious mental illness: a subgroup analysis of a randomized trial. J Clin Psychiatry. 2016 Mar;77(3):e320-6. doi: 10.4088/JCP.15m10074.
• Evins AE, Cather C, Pratt SA, Pachas GN, Hoeppner SS, Goff DC, Achtyes ED, Ayer D, Schoenfeld DA. Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder: a randomized clinical trial. JAMA. 2014 Jan 8;311(2):145-54. doi: 10.1001/jama.2013.285113.

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