Varenicline and Smoking Cessation in Schizophrenia (VSCS)

• Smoking abstinence [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Measured by self-report of the subject and verified by exhaled carbon monoxide and blood/urine tests for nicotine and its break-down product cotinine.
  
  

• Reduction in smoking [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Successful outcome will be defined as a 50% or greater reduction in self-reported cigarettes per day and a 30% greater reduction in carbon monoxide and cotinine levels.
  
  
• Positive and Negative Symptoms of Schizophrenia [ Time Frame: Each week for the 12 weeks of the study ] [ Designated as safety issue: Yes ]
  These will be measured with the Positive and Negative Syndrome Scale, a clinical evaluation of the presence/absence and severity of principal positive and negative symptoms of schizophrenia
  
  
• Impulsivity and Inattention [ Time Frame: At the beginning of the study and at weeks 4, 8, and 12 ] [ Designated as safety issue: No ]
  Impulsivity and inattention will be measured using the continuous performance test.
  
  
• Side effects [ Time Frame: Each week for the 12 weeks of the study ] [ Designated as safety issue: Yes ]
  Side effects will be monitored by a physician and/or assistant and recorded (SEP). All patients withdrawn from the study because of emerging side effects will be followed until the side effects are resolved
  
  
• Abstinence-related symptoms [ Time Frame: Recorded at weeks 0, 4, 8, and 12 of the study ] [ Designated as safety issue: No ]
  These symptoms will be assessed using the Minnesota Nicotine Withdrawl Scale, evaluating symptoms such as irritability, tension/anxiety, craving for cigarettes, etc
  
  
• Suicidality [ Time Frame: Measured each week of the 12 week study ] [ Designated as safety issue: Yes ]
  Patients are assessed at each visit with regards to depression and suicidiality using two other psychometric tests: the Brief Psychiatric Rating Scale (BPRS) and the Beck Depression Inventory (BDI). Specifically, item 4 of the BPRS and item 9 of the BDI ask about suicidal ideation. Additionally on weeks 0, 4, 8, and 12 the Columbia Suicide Severity Rating Scale (C-SSRS) will be employed.
  
  
• Abnormal movements [ Time Frame: Each week of the 12 week study ] [ Designated as safety issue: Yes ]
  The Simpson-Angus Scale, will be used to evaluate patients experiencing neuroleptic-induced parkinsonism and other extrapyramidal side effects. Additionally, the Abnormal Involuntary Movement Scale will be used to assess abnormal involuntary movements associated with antipsychotic drugs, such as tardive dystonia and dyskinesia and akathisia, as well as 'spontaneous' motor disturbance related to the illness itself
  
  
• Vital Signs [ Time Frame: Each week of the 12 week study ] [ Designated as safety issue: Yes ]
  blood pressure, pulse, and weight will be measured.
  
  

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.