The Pharmacogenetic Study , Readiness to Change, and Pharmacological Intervention for Smoking Cessation in Schizophrenia
Condition: Tobacco Dependence; Schizophrenia
MeSH terms: Tobacco Use Disorder; Schizophrenia
Study type: Interventional
Phase: Phase 4

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).
    

Intervention name(s): Hihg-doseNRT, Low-dose NRT, bupropion
Intervention type(s): Drug
Intervention MeSH terms: Bupropion
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Schizophrenia; NRT; Bupropion; Stages of change