Varenicline and Smoking Cessation in Schizophrenia

NCT ID: NCT01111149

Last Updated: 2014-07-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2012-08-31

Brief Summary

There is a strong association between smoking and schizophrenia with prevalence rates ranging from 74% to 90%, versus a national average of 30% in nonschizophrenic individuals. A number of hypotheses have been proposed to explain the relationship between high smoking rates and schizophrenia, mostly relating to self-medication primarily for the negative symptoms of schizophrenia. Smoking cessation rates among schizophrenic patients are considerably lower than for other psychiatric disorders. The negative health effects of smoking increase the morbidity and mortality in schizophrenic patients. Currently, the efficacy of bupropion HCl in the treatment of smoking by schizophrenic subjects is inconclusive, and there have not been any published studies of the efficacy of varenicline in schizophrenic subjects. As varenicline appears to be a promising treatment in non-psychiatric patients, it would be useful to expand these studies to examine its effects in schizophrenic patients. Identifying effective and safe means of smoking cessation for this vulnerable population has the potential to reduce morbidity and mortality among individuals with schizophrenia.

Detailed Description

There is a strong association between smoking and schizophrenia with prevalence rates ranging from 74% to 90%, versus a national average of 30% in nonschizophrenic individuals. A number of hypotheses have been proposed to explain the relationship between high smoking rates and schizophrenia, mostly relating to self-medication primarily for the negative symptoms of schizophrenia. Smoking cessation rates among schizophrenic patients are considerably lower than for other psychiatric disorders. The negative health effects of smoking increase the morbidity and mortality in schizophrenic patients. The smoking cessation agent bupropion HCl has been tested in schizophrenics, but the results on its efficacy are inconclusive. Recent works by different laboratories have shown the safety and efficacy of varenicline, a partial alpha4beta2 and full alpha7 nicotinic acetylcholine receptor agonist, as a smoking cessation agent. However, to date, no published studies have tested the safety and efficacy of varenicline in treatment of nicotine dependence in schizophrenic patients. As varenicline appears to be a promising treatment in non-psychiatric patients, it would be beneficial to examine its effects in schizophrenic patients. The central hypothesis of this application is that treatment with varenicline will safely increase smoking abstinence rates in schizophrenic patients when compared to those receiving placebo. This central hypothesis will be tested and the objectives of this application accomplished by pursuing two Specific Aims: 1) Treatment with varenicline or bupropion HCl for a period of three months will increase smoking abstinence rates in schizophrenic patents when compared to placebo; and 2) Treatment with varenicline or bupropion HCl for a period of three months will not increase psychosis in schizophrenic patients when compared to placebo. For our General Investigational Plan, we will employ a double-blind randomized placebo controlled study to assess varenicline's safety and efficacy. It is our expectation that we will demonstrate that varenicline is safe and effective in decreasing smoking rates in schizophrenic patients without exacerbating psychotic symptoms. Such outcomes will be significant, because they will offer a new treatment for smoking cessation in this vulnerable population.

Conditions

Schizophrenia; Smoking Cessation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sugar Pill

Sugar pill will be given to patients as a comparison group to the active varenicline group. In the fist week, one placebo pill will be given per patient, followed by 2 pills per day for the remaining 12 weeks of the study.

Group Type: PLACEBO_COMPARATOR

Sugar Pill

Intervention Type: OTHER

Sugar pill created and masked by the pharmacy to be used as a control.

Varenicline

Varenicline has not previously been examined for its efficacy and safety in subjects with schizophrenia. Subjects in the varenicline group will receive one 1mg pill/day for week 0, followed by two 1mg pills/day for the rest of the study. This is an experimental group to be compared against both placebo and bupropion HCl.

Group Type: EXPERIMENTAL

Varenicline

Intervention Type: DRUG

Subjects in the varenicline group will receive one 1mg pill/day for week 0, followed by two 1mg pills/day for the rest of the study.

Bupropion HCl

Bupropion HCl is an established smoking cessation agent and will be used to compare its efficacy and safety against varenicline. Subjects in the Bupropion HCl group will receive one 150mg pill/day for week 0, followed by two 150mg pills/day for the rest of the study.

Group Type: ACTIVE_COMPARATOR

Bupropion HCl

Intervention Type: DRUG

in the Bupropion HCl group will receive one 150mg pill/day for week 0, followed by two 150mg pills/day for the rest of the study

Interventions

Sugar Pill

Sugar pill created and masked by the pharmacy to be used as a control.

Intervention Type: OTHER

Varenicline

Subjects in the varenicline group will receive one 1mg pill/day for week 0, followed by two 1mg pills/day for the rest of the study.

Intervention Type: DRUG

Bupropion HCl

in the Bupropion HCl group will receive one 150mg pill/day for week 0, followed by two 150mg pills/day for the rest of the study

Intervention Type: DRUG

Other Intervention Names

Chantix; Wellbutrin; Zyban

Eligibility Criteria

Inclusion Criteria

• Male or female subjects, 18-75 years old
• Diagnosis of schizophrenia or schizoaffective disorder based on Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria
• Smoking at least 10 cigarettes per day
• Weight of at least 100 lbs (45.4 kg)
• Motivation to quit smoking
• Stabilized psychotic symptoms
• Provision of informed consent for testing and treatment

Exclusion Criteria

• Serious cardiac, renal, hypertensive, pulmonary, endocrine, or neurologic disorder
• Seizure disorder, recent withdrawal from alcohol or anxiolytics
• History of bulimia nervosa, anorexia nervosa, or dementia
• History of depression, panic, or bipolar disorders
• Pregnancy or lactation
• Prior use of varenicline or bupropion HCl within three months prior to initiation of the study
• Current use of other smoking cessation treatments
• Regular use of non-cigarette tobacco products (> than once/week)
• Past substance abuse (alcohol or non-nicotine containing drugs) in the preceding 6 months
• Patients with suicidal ideations or plans
• Florid psychosis or increasing psychosis following varenicline or bupropion HCl treatment
• History of, or current, alcohol dependence/abuse
• Current use of monoamine oxidase inhibitors (MAOI)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

S. Hossein Fatemi, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

University of Minnesota, University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Countries

United States

References

Yousefi MK, Folsom TD, Fatemi SH. A Review of Varenicline's Efficacy and Tolerability in Smoking Cessation Studies in Subjects with Schizophrenia. J Addict Res Ther. 2011 Dec 20;S4(1):3045. doi: 10.4172/2155-6105.S4-001.

Reference Type: BACKGROUND

PMID: 22514788 (View on PubMed)

Fatemi SH. Varenicline efficacy and tolerability in a subject with schizophrenia. Schizophr Res. 2008 Aug;103(1-3):328-9. doi: 10.1016/j.schres.2008.05.002. Epub 2008 Jun 24. No abstract available.

Reference Type: BACKGROUND

PMID: 18572388 (View on PubMed)

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 May;146(1-3):376-8. doi: 10.1016/j.schres.2013.02.015. Epub 2013 Mar 16. No abstract available.

Reference Type: RESULT

PMID: 23507358 (View on PubMed)

Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.

Reference Type: DERIVED

PMID: 37142273 (View on PubMed)

Other Identifiers

R01DA024674

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0904M64601

Identifier Type: -

Identifier Source: org_study_id