The Pharmacogenetic Study , Readiness to Change, and Pharmacological Intervention for Smoking Cessation in Schizophrenia

NCT ID: NCT00495352

Last Updated: 2010-04-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2008-12-31

Brief Summary

Cigarette smoking represents a major health problem for patients suffering from schizophrenia. Compared to the general population, schizophrenic patients are significantly more likely to be addicted to nicotine. They also are more likely to be heavy smokers, and tend to be exposed disproportionately to nicotine and other harmful ingredients in the cigarette because of the observed tendency to smoke down to the very end. Further, smoking in these patients may be associated with a higher risk for developing tardive dyskinesia All of these factors render schizophrenic patients a particularly vulnerable group for the detrimental effects of tobacco-related medical problems. Currently, there is little information available regarding the efficacy and utility of smoking cessation treatment methods, as well as factors that may predict patients' response to such treatments.

An important related issue is the influence of smoking, and its cessation, on the effects of the medications most of these patients rely upon for the control of their psychiatric symptoms. Although smoking has long been known to significantly alter the metabolism, and thus the effects, of most antipsychotics, the extent and clinical significance of these influences have rarely been assessed. It is unclear to what extent smoke cessation (as well as initiation) changes the side effect profiles of these medications, and whether such changes contribute towards the difficulties in patients' ability and/or willingness to stop smoking.

In addition, except pharmacological intervention, readiness to change may be an important factor affecting the outcomes of smoking reduction. Prochaska et al proposed the concept of stages of change to predict the response of quitting behavior for substance use. A lot of evidence support the stronger of readiness of change, the higher successful rate of quitting can be reached. Yet these results are largely found in many non-pharmacological intervention and smoking cessation programs for general population. Till now, no available study solely focus readiness of change quitting smoking behavior in NRT treatment for chronic schizophrenic patients. Thus, we have an a great interest in examining the association between the stages of change and the outcomes of smoking-cessation along with reduction among schizophrenic patients receiving transdermal nicotine patches.

In order to begin addressing these important issues, this application proposes to utilize state-of-the-art methodologies derived from the field of pharmacogenetics, molecular biology and clinical trials, to (1) examine short-term and long-term efficacy of standard treatment methods, such as the use of nicotine patches, in this population; (2) identify factors that might predict treatment responses; and, (3) examine the interactions between smoking and the effect of antipsychotics, as well as how such interactions might affect smoking cessation. (4) to examine the predictive value of the stages of change on smoking cessation and reduction outcomes in schizophrenic patients receiving different doses of nicotine replacement therapy (NRT) and bupropion as implemented in a randomized trial.

Detailed Description

Specific Aims

Accordingly, this proposal aims at testing the following major hypotheses:

1. Nicotine patch therapy and bupropion are effective in smoke cessation among motivated psychiatric outpatients with schizophrenia.

1a. High dose nicotine patch therapy is significantly more effective in inducing smoke cessation than regular dose nicotine patch therapy.

1b. Nicotine patch therapy and bupropion are more effective in inducing smoke cessation in those treated with "atypical" neuroleptics as compared to those treated with "typical" neuroleptics.

2. Response to nicotine patch therapy is associated with genetic polymorphisms of DRD2, dopamine transporter (DAT; SLC6A3), CYP2A6 and CYP2D6 genes.

3. Smoke cessation is associated with a significant decrease in the activity of CYP1A2, as well as a significant increase in the steady-state concentration of the neuroleptics received by the patients. This will lead to an increased incidence of treatment emergent side effects, which may be controlled by neuroleptic dose adjustment.

4. patients in the stage of preparation or contemplation (stronger readiness to quit smoking) are more likely to reduce smoking and stop smoking than those in the stage of precontemplation (weaker readiness to quitting smoking).

Conditions

Tobacco Dependence; Schizophrenia

Study Design

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

Study Groups

High-dose NRT, Low-dose NRT, bupropion

Group Type: ACTIVE_COMPARATOR

Hihg-doseNRT, Low-dose NRT, bupropion

Intervention Type: DRUG

Interventions

Hihg-doseNRT, Low-dose NRT, bupropion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Competent volunteers completing consent form
• Schizophreniform, schizoaffective,or psychotic disorder NOS based on DSMIV

Exclusion Criteria

• Severe life-threatening physical condition
• Pregnancy
• Fluroxamine treatment in the past 2 weeks
• Allergy to nicotine or caffeine

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Health Research Institutes, Taiwan

OTHER

Sponsor Role: collaborator

Department of Health, Executive Yuan, R.O.C. (Taiwan)

OTHER_GOV

Sponsor Role: collaborator

Yu-Li Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yu-Li Hospital

Principal Investigators

Tsuo-Hung Lan, MD, Ph.D

Role: STUDY_DIRECTOR

General Clinical Research Center, YuLi hospital

Locations

Yuli hospital, DOH

Yuli Townhsip, , Taiwan

Countries

Taiwan

Other Identifiers

MD-095-PP-05A

Identifier Type: -

Identifier Source: org_study_id