Schizophrenia, Smoking Cessation
Conditions
Keywords
Schizophrenia, Smoking cessation, Varenicline, Bupropion
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.
Interventions
DRUGBupropion 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
OTHERSugar Pill
Sugar pill created and masked by the pharmacy to be used as a control.
DRUGVarenicline
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.
Sponsors
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Smoking Abstinence - Serum/Urine Measurements | Week 12 | Measured by blood/urine tests for nicotine and its break-down product cotinine. |
| Smoking Abstinence - Number of Cigarettes Smoked | Week 12 | Number of cigarettes smoked at week 12 of the study by self-report. |
| Smoking Abstinence - Exhaled Carbon Monoxide | Week 12 | Exhaled carbon monoxide as a biochemical verification of smoking abstinence. Values below are for week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impulsivity and Inattention | Week 12 | Impulsivity and inattention will be measured using the continuous performance test. Individuals were tasked with 359 items divided six blocks (59 in block 1, 60 in blocks 2-6). Omissions result from the failure to respond to target letters. CPT% Omissions measures the percentage of responses that qualify as omissions made during the test. Higher scores indicate increased inattention. Commissions result from responses given to non-targets. CPT% Commissions measures the percentage of responses that qualify as commissions made during the test. Higher scores indicate increased inattention. Perseverations result from reaction time less than 100 ms. CPT% Perseveration % measures the percentage of responses that qualify as perseverations made during the test. The higher the score, the greater impulsivity. |
| Side Effects | Week 12 | 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. Each item is scored based on a scale of 0=none; 1=mild; 2=moderate; and 3=severe. Below, the data are shown for participants experiencing symptoms on week 12 of the study. |
| Abstinence-related Symptoms - MNWS and FTND | Week 12 | Minnesota Nicotine Withdrawal Scale (MNWS), a patient-reported measure of nicotine withdrawal symptoms and cravings. Eight items are listed, including craving for cigarettes, irritability, frustration, or anger, anxiety, etc scored on a five point scale from 0 (normal) to 5 (severe). Patients are asked for responses for the past 24 hours and past seven days (minimum 0, maximum 32; for each subscale). The higher the score, the greater the dependence. Additionally, one question (minimum score 1, maximum score 4 measures the individual's confidence in resisting strong urges to smoke. The higher the score on this question, the greater the individual's confidence in resisting smoking urges. The Fagerstrom Test for Nicotine Dependence measures nicotine dependence and consists of six questions with a total minimum score of 0 and a maximum score of 10. The higher the score, the greater the dependence on nicotine. |
| Depression | Week 12 | Beck Depression Inventory (BDI), a self-report rating inventory measuring characteristic attitudes and symptoms of depression consisting of 21 items with each item rated on a four point scale (0=not present to 3=severe). The accepted ranges are as follows: 0 to 9 indicates no depression, 10 to 18 indicates mild to moderate depression, 19 to 29 indicates moderate to severe depression and 30 to 63 indicates severe depression. |
| Abnormal Movements - BAS and SAS | Week 12 | Barnes Akathisia Scale (BAS), a widely-used measurement of drug-induced akathisia. It consists of 4 questions with questions 1-3 scored on a scale of 0-3 with 0=normal and 3=severe (minimum score 0, maximum score 9; while item 4 is a global clinical assessment of akathisia rated on a scale of 0 (normal) to 5 (severe). The higher the score on each subsclae, the greater the severity of akathisia. Simpson-Angus Scale (SAS), a 10-item instrument used to evaluate patients experiencing neuroleptic-induced parkinsonism and other extrapyramidal side effects. Items are rated for severity on a 0-4 scale, with 0 being normal and 4 being severe. Minimum = 0; Maximum = 40. The higher the score, the greater the severity. |
| Vital Signs - Weight | Week 12 | Weight will be measured for each participant. Values listed below are for week 12. |
| Vital Signs - Pulse | Week 12 | Pulse will be measured. The values below were measured at week 12 of the study. |
| Suicidality | Week 12 | The Columbia-Suicide Severity Rating Scale (C-SSRS), is a survey intended to quantify the severity of suicidal ideation and behavior. The questionaire for suicidal ideation consists of 5 questions with yes (1) /no (0) answers. If answers to questions 1 and 2 are no, questions 3-5 are skipped. Minimum of 0; Maximum of 5. The questionaire for suicidal behavior consists of seven questions rated 0 for no and 1 for yes. The minimum score is 0 and the maximum score is 7. In each case, the higher the score, the greater the severity. |
| Vital Signs | Week 12 | blood pressure will be measured. |
| General Psychopathology | Week 12 | Brief Psychiatric Rating Scale (BPRS), an 24-item scale measuring positive symptoms, general psychopathology, and affective symptoms commonly used for schizophrenia with each item rated on a scale of 1-7 with 1=not present and 7=severe. The minimum score is 24 and the maximum score is 168. We have used five subscales as recommended by Dingemans et al., 1995: Positive subscale (minimum score 6; maximum score 42); Negative subscale (minimum score 5; maximum score 35); Depressed subscale (minimum score 5; maximum score 35); Mania subscale (minimum score 6; maximum score 42); and Disorientation subscale (minimum score 2; maximum score 14) . For both the total score and the subscale scores, the higher the score, the greater the symptom severity. We used the BPRS version 4.0. Dingemans PMAJ, Linszen DH, Lenoir ME, Smeets RMW, 1995. Component structure of the expanded Brief Psychiatric Rating Scale (BPRS-E). Psychopharmacology 122:263-267. |
| Hit Reaction Time - CPT | Week 12 | The hit reaction time is the average speed of correct responses for the entire test given in milliseconds. The higher the score, the slower the speed. The standard error is a measure of response speed consistency. The higher the overall standard error, the greater inconsistency in the response speed. The values below were measured at week 12. |
| Variability of Standard Error - CPT | Week 12 | Variability of Standard Error (VSE) is a measure of response speed consistency. VSE measures within respondent variability. That is, the amount of variability the individual shows in 18 separate segments of the Continuous Performance Test in relation to his or her own overall standard error. Although VSE is a different measure than Overall Standard Error, typically the two measures produce comparable results. The higher the VSE, the greater the inconsistency in the response speed. The values shown below are the VSE for Week 12. |
| Detectibility (d') of Continuous Performance Test | Week 12 | The value d' is a measure of the difference between the signal (non-X) and noise (X) distributions. As such, d' provides a means for assessing an individual's discriminative power since, in general, the greater the difference between the signal and noise distributions, the better the ability to distinguish and detect X and non-X stimuli. The lower the score, the better the detectability. Values shown below are for week 12. |
| Response Style Indicator (Beta) for CPT | Week 12 | Beta represents an individual's response tendency: Some individuals are cautious and choose not to respond very often. Conceptually, such individuals want to make sure they are correct when they give a response. Higher values of Beta reflect this response style. The emphasis is on avoiding commission errors. Other individuals respond more freely to make sure they respond to most or all targets, and they tend to be less concerned about mistakenly responding to a non-target. Lower values of Beta are produced by this response style. Values shown below were obtained at week 12. |
| Abstinence Related Symptoms - WISDM | Week 12 | The Wisconsin Inventory of Smoking Dependence Motives (WISDM) consists of 68 items regarding smoking. Each item is rated on a scale of 1 (not true of me at all) to 7 (extremely true of me) leading to a minimum score of 68 and a maximum score of 476. The higher the score, the greater the dependence. Four of the items are grouped into a Craving subscale (minimum 4, maximum 28), the greater the score, the greater the craving. Five of the items are grouped into a Cognition subscale (minimum 5, maximum 35), the higher the score, the greater reliance on cigarette smoking for cognitive enhancement. WISDM scoring based on the original article by Piper et al., 2004. A multiple motives approach to tobacco dependence: the Wisconsin inventory of smoking dependence motives (WISDM-68). Journal of Consulting and Clinical Psychology 72:139-154. |
| Urge to Smoke - MNWS | Week 12 | The Minnesota Nicotine Withdrawal Scale (MNWS) includes two items where individuals are asked to 1) declare the percentage of time they had an urge to smoke (MNWS % Urge to Smoke); and 2) declare the percentage of time they had a strong urge to smoke (MNWS % Strong Urge). For each case, percentages range from 0% to 100% - the higher the percentage, the greater urge to smoke. |
| Abnormal Movements - AIMS | Week 12 | Abnormal Involuntary Movement Scale (AIMS), to assess abnormal involuntary movements associated with antipsychotic drugs. There are 10 questions, based on a five-point scale ranging from 0 (none) to 4 (severe). Items 11-14 are yes/no questions that have no impact on the score. The Total Score is the sum of questions 1-7 (minimum = 0; maximum = 28). The severity index consists of one question (item 8; rated 0=none to 4=severe) based on the rater's observation of abnormal movements The AIMS Global Score is the sum of three questions (each item rated 0=none to 4=severe) regarding abnormal movements overall (minimum score 0, maximum score 12). For the total score and subscores, the higher the score, the greater the severity of abnormal movements. Scoring is based on the chapter: Guy W (2000), Abnormal Involuntary Movement Scale (AIMS), in: Handbook of Psychiatric Measures (Rush AJ Jr, et al., eds). APA Publishing: Washington DC: pp. 166-167. |
| Positive Symptoms of Schizophrenia (SAPS) | Week 12 | Scale for the Assessment of Positive Symptoms (SAPS), a well-established test, used to assess the presence of psychotic symptoms of schizophrenia. There are 34 items rated on a scale of 0-5 with 0=none and 5=severe for a minimum score of 0 and a maximum score of 170. There are 4 subscales: Hallucinations (minimum score 0; maximum score 35); Delusions (minimum score 0; maximum score 65); Bizarre Behavior (minimum score 0; maximum score 25); Positive Formal Thought Disorder (minimum score 0; maximum score 45). Each subscale contains one additional question as a Global Rating - or overall measure for that particular subscale. The sum of these questions constitutes the Total Global Score (minimum 0, maximum 20). The values for the Global items are included in the Total Composite score. In each case, the higher the score, the greater the severity of symptoms. |
| Reduction in Smoking | Week 12 | 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. Measured at week 12 |
| Negative Symptoms of Schizophrenia - SANS | Week 12 | Scale for the Assessment of Negative Symptoms (SANS) a well-established test, used to assess the presence of psychosis or negative symptoms of schizophrenia. It consists of 25 questions rated on a scale of 0 (none) to 5 (severe). With a total score range of 0 to 125 points. There are 6 subscales: Affective Flattening or Blunting - (minimum, 0; maximum 35); Inappropriate Affect (minimum, 0; maximum 5); Alogia (minimum 0; maximum 25); Avolition-Apathy (minimum 0; maximum 20); Anhedonia-Asociality (minimum 0; maximum 25); Attention (minimum 0; maximum 15). Each subscale (except for Inappropriate Affect) contains one additional question as a Global Rating - or overall measure for that particular subscale. The sum of these questions constitutes the Total Global Score (minimum 0, maximum 25). The global questions are included within the Total Composite score. In each case, the larger the score, the more severe the symptoms. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from 12/15/2009 through 4/03/2012. Fliers advertising the study were placed in medical clinics. Additionally, advertisements were placed in local newspapers City Pages and The Minneapolis Star Tribune.
Pre-assignment details
Enrolled participants were excluded from the trial before assignment to groups if they no longer showed interest in the study or failed drug screens.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Sugar Pill: Sugar pill created and masked by the pharmacy to be used as a control. | 9 |
| 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.
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. | 6 |
| 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.
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 | 9 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Sugar Pill | Bupropion HCl | Varenicline |
|---|---|---|---|---|
| Age, Continuous | 41.46 years STANDARD_DEVIATION 11.63 | 41.4 years STANDARD_DEVIATION 9.8 | 43 years STANDARD_DEVIATION 8.44 | 40.4 years STANDARD_DEVIATION 15.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 9 Participants | 9 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 8 Participants | 6 Participants | 3 Participants |
| Region of Enrollment United States | 24 participants | 9 participants | 9 participants | 6 participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 19 Participants | 7 Participants | 7 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 7 | 0 / 5 | 0 / 5 |
| serious Total, serious adverse events | 0 / 7 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Smoking Abstinence - Exhaled Carbon Monoxide
Exhaled carbon monoxide as a biochemical verification of smoking abstinence. Values below are for week 12.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugar Pill | Smoking Abstinence - Exhaled Carbon Monoxide | 21.14 parts per million | Standard Deviation 18.51 |
| Varenicline | Smoking Abstinence - Exhaled Carbon Monoxide | 17 parts per million | Standard Deviation 13.53 |
| Bupropion HCl | Smoking Abstinence - Exhaled Carbon Monoxide | 22.6 parts per million | Standard Deviation 19.14 |
Comparison: Statistical analysis for Smoking Abstinence - Exhaled Carbon Monoxide (Week 12)p-value: >0.05ANOVA
Primary
Smoking Abstinence - Number of Cigarettes Smoked
Number of cigarettes smoked at week 12 of the study by self-report.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugar Pill | Smoking Abstinence - Number of Cigarettes Smoked | 19.71 number of cigarettes smoked | Standard Deviation 22.77 |
| Varenicline | Smoking Abstinence - Number of Cigarettes Smoked | 9.4 number of cigarettes smoked | Standard Deviation 5.47 |
| Bupropion HCl | Smoking Abstinence - Number of Cigarettes Smoked | 17.1 number of cigarettes smoked | Standard Deviation 17.28 |
Comparison: Statistical analysis for Smoking Abstinence - Number of Cigarettes Smoked (Week 12)p-value: >0.05ANOVA
Primary
Smoking Abstinence - Serum/Urine Measurements
Measured by blood/urine tests for nicotine and its break-down product cotinine.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Smoking Abstinence - Serum/Urine Measurements | Serum Cotinine (Week 12) | 198.67 ng/mL | Standard Deviation 129.84 |
| Sugar Pill | Smoking Abstinence - Serum/Urine Measurements | Serum Nicotine (Week 12) | 22.57 ng/mL | Standard Deviation 24.23 |
| Sugar Pill | Smoking Abstinence - Serum/Urine Measurements | Urine Cotinine (Week 12) | 772 ng/mL | Standard Deviation 381.19 |
| Sugar Pill | Smoking Abstinence - Serum/Urine Measurements | Urine Nicotine (Week 12) | 820 ng/mL | Standard Deviation 301.46 |
| Varenicline | Smoking Abstinence - Serum/Urine Measurements | Urine Nicotine (Week 12) | 613.25 ng/mL | Standard Deviation 243.29 |
| Varenicline | Smoking Abstinence - Serum/Urine Measurements | Serum Nicotine (Week 12) | 6 ng/mL | Standard Deviation 9.59 |
| Varenicline | Smoking Abstinence - Serum/Urine Measurements | Serum Cotinine (Week 12) | 207 ng/mL | Standard Deviation 130.73 |
| Varenicline | Smoking Abstinence - Serum/Urine Measurements | Urine Cotinine (Week 12) | 699.6 ng/mL | Standard Deviation 527.45 |
| Bupropion HCl | Smoking Abstinence - Serum/Urine Measurements | Urine Cotinine (Week 12) | 614.75 ng/mL | Standard Deviation 469.54 |
| Bupropion HCl | Smoking Abstinence - Serum/Urine Measurements | Urine Nicotine (Week 12) | 412.75 ng/mL | Standard Deviation 487.9 |
| Bupropion HCl | Smoking Abstinence - Serum/Urine Measurements | Serum Cotinine (Week 12) | 213.8 ng/mL | Standard Deviation 137.6 |
| Bupropion HCl | Smoking Abstinence - Serum/Urine Measurements | Serum Nicotine (Week 12) | 15.4 ng/mL | Standard Deviation 11.61 |
Comparison: Statistical Analysis for Serum Cotinine at Week 12p-value: >0.05ANOVA
Comparison: Statistical Analysis for Serum Nicotine at Week 12p-value: >0.05ANOVA
Comparison: Statistical Analysis for Urine Cotinine at Week 12p-value: >0.05ANOVA
Comparison: Statistical Analysis for Urine Nicotine at Week 12p-value: >0.05ANOVA
Secondary
Abnormal Movements - AIMS
Abnormal Involuntary Movement Scale (AIMS), to assess abnormal involuntary movements associated with antipsychotic drugs. There are 10 questions, based on a five-point scale ranging from 0 (none) to 4 (severe). Items 11-14 are yes/no questions that have no impact on the score. The Total Score is the sum of questions 1-7 (minimum = 0; maximum = 28). The severity index consists of one question (item 8; rated 0=none to 4=severe) based on the rater's observation of abnormal movements The AIMS Global Score is the sum of three questions (each item rated 0=none to 4=severe) regarding abnormal movements overall (minimum score 0, maximum score 12). For the total score and subscores, the higher the score, the greater the severity of abnormal movements. Scoring is based on the chapter: Guy W (2000), Abnormal Involuntary Movement Scale (AIMS), in: Handbook of Psychiatric Measures (Rush AJ Jr, et al., eds). APA Publishing: Washington DC: pp. 166-167.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Abnormal Movements - AIMS | AIMS Severity Index (Week 12) | 0 units on a scale | Standard Deviation 0 |
| Sugar Pill | Abnormal Movements - AIMS | AIMS Total (Week 12) | 0.71 units on a scale | Standard Deviation 1.25 |
| Sugar Pill | Abnormal Movements - AIMS | AIMS Global Score (Week 12) | 0 units on a scale | Standard Deviation 0 |
| Varenicline | Abnormal Movements - AIMS | AIMS Global Score (Week 12) | 0.2 units on a scale | Standard Deviation 0.45 |
| Varenicline | Abnormal Movements - AIMS | AIMS Severity Index (Week 12) | 0.2 units on a scale | Standard Deviation 0.45 |
| Varenicline | Abnormal Movements - AIMS | AIMS Total (Week 12) | 1 units on a scale | Standard Deviation 1.41 |
| Bupropion HCl | Abnormal Movements - AIMS | AIMS Total (Week 12) | 1.40 units on a scale | Standard Deviation 2.19 |
| Bupropion HCl | Abnormal Movements - AIMS | AIMS Severity Index (Week 12) | 0.4 units on a scale | Standard Deviation 0.89 |
| Bupropion HCl | Abnormal Movements - AIMS | AIMS Global Score (Week 12) | 0.6 units on a scale | Standard Deviation 1.34 |
Comparison: Statistical analysis for AIMS Total (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for AIMS Severity Index (Week 12)p-value: >0.05ANOVA
Comparison: Statistical Analysis for AIMS Global Score (Week 12)p-value: >0.05ANOVA
Secondary
Abnormal Movements - BAS and SAS
Barnes Akathisia Scale (BAS), a widely-used measurement of drug-induced akathisia. It consists of 4 questions with questions 1-3 scored on a scale of 0-3 with 0=normal and 3=severe (minimum score 0, maximum score 9; while item 4 is a global clinical assessment of akathisia rated on a scale of 0 (normal) to 5 (severe). The higher the score on each subsclae, the greater the severity of akathisia. Simpson-Angus Scale (SAS), a 10-item instrument used to evaluate patients experiencing neuroleptic-induced parkinsonism and other extrapyramidal side effects. Items are rated for severity on a 0-4 scale, with 0 being normal and 4 being severe. Minimum = 0; Maximum = 40. The higher the score, the greater the severity.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Abnormal Movements - BAS and SAS | BAS Items 1-3 (Week 12) | 0.57 units on a scale | Standard Deviation 0.98 |
| Sugar Pill | Abnormal Movements - BAS and SAS | SAS (Week 12) | 0.2 units on a scale | Standard Deviation 0.24 |
| Sugar Pill | Abnormal Movements - BAS and SAS | BAS Item 4 (Week 12) | 0.29 units on a scale | Standard Deviation 0.49 |
| Varenicline | Abnormal Movements - BAS and SAS | BAS Items 1-3 (Week 12) | 0.6 units on a scale | Standard Deviation 0.89 |
| Varenicline | Abnormal Movements - BAS and SAS | SAS (Week 12) | 0.76 units on a scale | Standard Deviation 0.76 |
| Varenicline | Abnormal Movements - BAS and SAS | BAS Item 4 (Week 12) | 0.4 units on a scale | Standard Deviation 0.55 |
| Bupropion HCl | Abnormal Movements - BAS and SAS | SAS (Week 12) | 0.42 units on a scale | Standard Deviation 0.8 |
| Bupropion HCl | Abnormal Movements - BAS and SAS | BAS Item 4 (Week 12) | 0.2 units on a scale | Standard Deviation 0.45 |
| Bupropion HCl | Abnormal Movements - BAS and SAS | BAS Items 1-3 (Week 12) | 0.4 units on a scale | Standard Deviation 0.89 |
Comparison: Statistical analysis for SAS (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for BAS items 1-3 (week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for BAS item 4 (Week 12)p-value: >0.05ANOVA
Secondary
Abstinence-related Symptoms - MNWS and FTND
Minnesota Nicotine Withdrawal Scale (MNWS), a patient-reported measure of nicotine withdrawal symptoms and cravings. Eight items are listed, including craving for cigarettes, irritability, frustration, or anger, anxiety, etc scored on a five point scale from 0 (normal) to 5 (severe). Patients are asked for responses for the past 24 hours and past seven days (minimum 0, maximum 32; for each subscale). The higher the score, the greater the dependence. Additionally, one question (minimum score 1, maximum score 4 measures the individual's confidence in resisting strong urges to smoke. The higher the score on this question, the greater the individual's confidence in resisting smoking urges. The Fagerstrom Test for Nicotine Dependence measures nicotine dependence and consists of six questions with a total minimum score of 0 and a maximum score of 10. The higher the score, the greater the dependence on nicotine.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Abstinence-related Symptoms - MNWS and FTND | FTND (Week 12) | 4.86 units on a scale | Standard Deviation 1.77 |
| Sugar Pill | Abstinence-related Symptoms - MNWS and FTND | MNWS 24 Hour Total (Week 12) | 7.29 units on a scale | Standard Deviation 7.04 |
| Sugar Pill | Abstinence-related Symptoms - MNWS and FTND | MNWS Resistance (Week 12) | 2.71 units on a scale | Standard Deviation 1.11 |
| Sugar Pill | Abstinence-related Symptoms - MNWS and FTND | MNWS 7 day total (Week 12) | 9.14 units on a scale | Standard Deviation 4.98 |
| Varenicline | Abstinence-related Symptoms - MNWS and FTND | MNWS 24 Hour Total (Week 12) | 8.2 units on a scale | Standard Deviation 7.36 |
| Varenicline | Abstinence-related Symptoms - MNWS and FTND | MNWS 7 day total (Week 12) | 11 units on a scale | Standard Deviation 4.64 |
| Varenicline | Abstinence-related Symptoms - MNWS and FTND | FTND (Week 12) | 5.2 units on a scale | Standard Deviation 1.48 |
| Varenicline | Abstinence-related Symptoms - MNWS and FTND | MNWS Resistance (Week 12) | 3.4 units on a scale | Standard Deviation 0.55 |
| Bupropion HCl | Abstinence-related Symptoms - MNWS and FTND | MNWS Resistance (Week 12) | 2.4 units on a scale | Standard Deviation 1.14 |
| Bupropion HCl | Abstinence-related Symptoms - MNWS and FTND | MNWS 24 Hour Total (Week 12) | 6.60 units on a scale | Standard Deviation 4.67 |
| Bupropion HCl | Abstinence-related Symptoms - MNWS and FTND | FTND (Week 12) | 4.4 units on a scale | Standard Deviation 3.36 |
| Bupropion HCl | Abstinence-related Symptoms - MNWS and FTND | MNWS 7 day total (Week 12) | 5.80 units on a scale | Standard Deviation 4.27 |
Comparison: Statistical analysis for FTND (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for MNWS 24 Hour Total (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for MNWS 7 day total (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for MNWS Resistance (Week 12)p-value: >0.05ANOVA
Secondary
Abstinence Related Symptoms - WISDM
The Wisconsin Inventory of Smoking Dependence Motives (WISDM) consists of 68 items regarding smoking. Each item is rated on a scale of 1 (not true of me at all) to 7 (extremely true of me) leading to a minimum score of 68 and a maximum score of 476. The higher the score, the greater the dependence. Four of the items are grouped into a Craving subscale (minimum 4, maximum 28), the greater the score, the greater the craving. Five of the items are grouped into a Cognition subscale (minimum 5, maximum 35), the higher the score, the greater reliance on cigarette smoking for cognitive enhancement. WISDM scoring based on the original article by Piper et al., 2004. A multiple motives approach to tobacco dependence: the Wisconsin inventory of smoking dependence motives (WISDM-68). Journal of Consulting and Clinical Psychology 72:139-154.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Abstinence Related Symptoms - WISDM | WISDM Cognition (Week 12) | 11.57 units on a scale | Standard Deviation 8.87 |
| Sugar Pill | Abstinence Related Symptoms - WISDM | WISDM Total (Week 12) | 229.14 units on a scale | Standard Deviation 93.31 |
| Sugar Pill | Abstinence Related Symptoms - WISDM | WISDM Craving (Week 12) | 15.14 units on a scale | Standard Deviation 5.73 |
| Varenicline | Abstinence Related Symptoms - WISDM | WISDM Cognition (Week 12) | 15.4 units on a scale | Standard Deviation 5.81 |
| Varenicline | Abstinence Related Symptoms - WISDM | WISDM Total (Week 12) | 229.4 units on a scale | Standard Deviation 52.03 |
| Varenicline | Abstinence Related Symptoms - WISDM | WISDM Craving (Week 12) | 14.2 units on a scale | Standard Deviation 3.35 |
| Bupropion HCl | Abstinence Related Symptoms - WISDM | WISDM Total (Week 12) | 270.6 units on a scale | Standard Deviation 181.21 |
| Bupropion HCl | Abstinence Related Symptoms - WISDM | WISDM Craving (Week 12) | 18 units on a scale | Standard Deviation 11.11 |
| Bupropion HCl | Abstinence Related Symptoms - WISDM | WISDM Cognition (Week 12) | 23.2 units on a scale | Standard Deviation 16.16 |
Comparison: Statistical analysis for WISDM Total (Week 12)p-value: >0.05ANOVA
Comparison: Statistical Analysis for WISDM Cognition (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for WISDM Craving (Week 12)p-value: >0.05ANOVA
Secondary
Depression
Beck Depression Inventory (BDI), a self-report rating inventory measuring characteristic attitudes and symptoms of depression consisting of 21 items with each item rated on a four point scale (0=not present to 3=severe). The accepted ranges are as follows: 0 to 9 indicates no depression, 10 to 18 indicates mild to moderate depression, 19 to 29 indicates moderate to severe depression and 30 to 63 indicates severe depression.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugar Pill | Depression | 3.71 units on a scale | Standard Deviation 3.55 |
| Varenicline | Depression | 8.6 units on a scale | Standard Deviation 9.94 |
| Bupropion HCl | Depression | 5.4 units on a scale | Standard Deviation 6.99 |
Comparison: Statistical analysis of Beck Depression Inventory (Week 12)p-value: >0.05ANOVA
Secondary
Detectibility (d') of Continuous Performance Test
The value d' is a measure of the difference between the signal (non-X) and noise (X) distributions. As such, d' provides a means for assessing an individual's discriminative power since, in general, the greater the difference between the signal and noise distributions, the better the ability to distinguish and detect X and non-X stimuli. The lower the score, the better the detectability. Values shown below are for week 12.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugar Pill | Detectibility (d') of Continuous Performance Test | 0.71 unitless | Standard Deviation 0.54 |
| Varenicline | Detectibility (d') of Continuous Performance Test | 1.32 unitless | Standard Deviation 0.8 |
| Bupropion HCl | Detectibility (d') of Continuous Performance Test | 1.09 unitless | Standard Deviation 0.68 |
Comparison: Statistical analysis for Detectibility (d') of Continuous Performance Test (Week 12)p-value: >0.05ANOVA
Secondary
General Psychopathology
Brief Psychiatric Rating Scale (BPRS), an 24-item scale measuring positive symptoms, general psychopathology, and affective symptoms commonly used for schizophrenia with each item rated on a scale of 1-7 with 1=not present and 7=severe. The minimum score is 24 and the maximum score is 168. We have used five subscales as recommended by Dingemans et al., 1995: Positive subscale (minimum score 6; maximum score 42); Negative subscale (minimum score 5; maximum score 35); Depressed subscale (minimum score 5; maximum score 35); Mania subscale (minimum score 6; maximum score 42); and Disorientation subscale (minimum score 2; maximum score 14) . For both the total score and the subscale scores, the higher the score, the greater the symptom severity. We used the BPRS version 4.0. Dingemans PMAJ, Linszen DH, Lenoir ME, Smeets RMW, 1995. Component structure of the expanded Brief Psychiatric Rating Scale (BPRS-E). Psychopharmacology 122:263-267.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | General Psychopathology | BPRS Negative Subscale - Week 12 | 6 units on a scale | Standard Deviation 1.15 |
| Sugar Pill | General Psychopathology | BPRS Total - Week 12 | 30 units on a scale | Standard Deviation 4.47 |
| Sugar Pill | General Psychopathology | BPRS Mania Subscale - Week 12 | 6.43 units on a scale | Standard Deviation 1.13 |
| Sugar Pill | General Psychopathology | BPRS Positive Subscale - Week 12 | 8.14 units on a scale | Standard Deviation 2.73 |
| Sugar Pill | General Psychopathology | BPRS Disorientation Subscale - Week 12 | 2 units on a scale | Standard Deviation 0 |
| Sugar Pill | General Psychopathology | BPRS Depression Subscale - Week 12 | 7.43 units on a scale | Standard Deviation 2.64 |
| Varenicline | General Psychopathology | BPRS Negative Subscale - Week 12 | 6.4 units on a scale | Standard Deviation 1.67 |
| Varenicline | General Psychopathology | BPRS Positive Subscale - Week 12 | 9 units on a scale | Standard Deviation 2.74 |
| Varenicline | General Psychopathology | BPRS Mania Subscale - Week 12 | 6.4 units on a scale | Standard Deviation 0.55 |
| Varenicline | General Psychopathology | BPRS Disorientation Subscale - Week 12 | 2 units on a scale | Standard Deviation 0 |
| Varenicline | General Psychopathology | BPRS Depression Subscale - Week 12 | 10.4 units on a scale | Standard Deviation 2.88 |
| Varenicline | General Psychopathology | BPRS Total - Week 12 | 34.2 units on a scale | Standard Deviation 3.96 |
| Bupropion HCl | General Psychopathology | BPRS Disorientation Subscale - Week 12 | 2 units on a scale | Standard Deviation 0 |
| Bupropion HCl | General Psychopathology | BPRS Total - Week 12 | 31.6 units on a scale | Standard Deviation 4.28 |
| Bupropion HCl | General Psychopathology | BPRS Negative Subscale - Week 12 | 7.4 units on a scale | Standard Deviation 1.52 |
| Bupropion HCl | General Psychopathology | BPRS Mania Subscale - Week 12 | 8 units on a scale | Standard Deviation 2.92 |
| Bupropion HCl | General Psychopathology | BPRS Depression Subscale - Week 12 | 6.2 units on a scale | Standard Deviation 1.79 |
| Bupropion HCl | General Psychopathology | BPRS Positive Subscale - Week 12 | 8 units on a scale | Standard Deviation 2.92 |
Comparison: Statistical analysis for BPRS Total - Week 12p-value: >0.05ANOVA
Comparison: Statistical analysis for BPRS Positive Subscale - Week 12p-value: >0.05ANOVA
Comparison: Statistical analysis for BPRS Negative Subscale - Week 12p-value: >0.05ANOVA
Comparison: Statistical analysis for Mania Subscale - Week 12p-value: >0.05ANOVA
Comparison: Statistical analysis for Disorientation Subscale - Week 12p-value: >0.05ANOVA
Comparison: Statistical analysis for BPRS Depression Subscale - Week 12p-value: >0.05ANOVA
Secondary
Hit Reaction Time - CPT
The hit reaction time is the average speed of correct responses for the entire test given in milliseconds. The higher the score, the slower the speed. The standard error is a measure of response speed consistency. The higher the overall standard error, the greater inconsistency in the response speed. The values below were measured at week 12.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Hit Reaction Time - CPT | Hit Reaction Time Standard Error (Week 12) | 7.20 milliseconds | Standard Deviation 4.83 |
| Sugar Pill | Hit Reaction Time - CPT | Hit Reaction Time (week 12) | 42.44 milliseconds | Standard Deviation 36.91 |
| Varenicline | Hit Reaction Time - CPT | Hit Reaction Time (week 12) | 67.61 milliseconds | Standard Deviation 34.47 |
| Varenicline | Hit Reaction Time - CPT | Hit Reaction Time Standard Error (Week 12) | 6.96 milliseconds | Standard Deviation 2 |
| Bupropion HCl | Hit Reaction Time - CPT | Hit Reaction Time (week 12) | 63.81 milliseconds | Standard Deviation 41.8 |
| Bupropion HCl | Hit Reaction Time - CPT | Hit Reaction Time Standard Error (Week 12) | 8.79 milliseconds | Standard Deviation 3.02 |
Comparison: Statistical analysis for Hit Reaction Time - CPT (Week 12)p-value: >0.05ANOVA
Secondary
Impulsivity and Inattention
Impulsivity and inattention will be measured using the continuous performance test. Individuals were tasked with 359 items divided six blocks (59 in block 1, 60 in blocks 2-6). Omissions result from the failure to respond to target letters. CPT% Omissions measures the percentage of responses that qualify as omissions made during the test. Higher scores indicate increased inattention. Commissions result from responses given to non-targets. CPT% Commissions measures the percentage of responses that qualify as commissions made during the test. Higher scores indicate increased inattention. Perseverations result from reaction time less than 100 ms. CPT% Perseveration % measures the percentage of responses that qualify as perseverations made during the test. The higher the score, the greater impulsivity.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Impulsivity and Inattention | CPT % Commissions (Week 12) | 36.11 Percentage of responses | Standard Deviation 22.64 |
| Sugar Pill | Impulsivity and Inattention | CPT % Omissions (Week 12) | 5.62 Percentage of responses | Standard Deviation 11.14 |
| Sugar Pill | Impulsivity and Inattention | Perseveration % (Week 12) | 0.57 Percentage of responses | Standard Deviation 0.86 |
| Varenicline | Impulsivity and Inattention | CPT % Commissions (Week 12) | 25 Percentage of responses | Standard Deviation 37.89 |
| Varenicline | Impulsivity and Inattention | CPT % Omissions (Week 12) | 0.68 Percentage of responses | Standard Deviation 1.04 |
| Varenicline | Impulsivity and Inattention | Perseveration % (Week 12) | 1.05 Percentage of responses | Standard Deviation 1.84 |
| Bupropion HCl | Impulsivity and Inattention | CPT % Omissions (Week 12) | 2.42 Percentage of responses | Standard Deviation 2.66 |
| Bupropion HCl | Impulsivity and Inattention | Perseveration % (Week 12) | 0.12 Percentage of responses | Standard Deviation 0.17 |
| Bupropion HCl | Impulsivity and Inattention | CPT % Commissions (Week 12) | 28.33 Percentage of responses | Standard Deviation 21.82 |
Comparison: Statistical analysis for CPT % Omissions (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for CPT% commissions (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for perseveration % (week 12)p-value: >0.05ANOVA
Secondary
Negative Symptoms of Schizophrenia - SANS
Scale for the Assessment of Negative Symptoms (SANS) a well-established test, used to assess the presence of psychosis or negative symptoms of schizophrenia. It consists of 25 questions rated on a scale of 0 (none) to 5 (severe). With a total score range of 0 to 125 points. There are 6 subscales: Affective Flattening or Blunting - (minimum, 0; maximum 35); Inappropriate Affect (minimum, 0; maximum 5); Alogia (minimum 0; maximum 25); Avolition-Apathy (minimum 0; maximum 20); Anhedonia-Asociality (minimum 0; maximum 25); Attention (minimum 0; maximum 15). Each subscale (except for Inappropriate Affect) contains one additional question as a Global Rating - or overall measure for that particular subscale. The sum of these questions constitutes the Total Global Score (minimum 0, maximum 25). The global questions are included within the Total Composite score. In each case, the larger the score, the more severe the symptoms.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Negative Symptoms of Schizophrenia - SANS | Inappropriate Affect (Week 12) | 0 units on a scale | Standard Deviation 0 |
| Sugar Pill | Negative Symptoms of Schizophrenia - SANS | SANS Avolition (Week 12) | 2 units on a scale | Standard Deviation 2.77 |
| Sugar Pill | Negative Symptoms of Schizophrenia - SANS | SANS Attention (Week 12) | 0 units on a scale | Standard Deviation 0 |
| Sugar Pill | Negative Symptoms of Schizophrenia - SANS | SANS Anhedonia (Week 12) | 1.57 units on a scale | Standard Deviation 1.99 |
| Sugar Pill | Negative Symptoms of Schizophrenia - SANS | SANS Total Global (Week 12) | 1.71 units on a scale | Standard Deviation 1.5 |
| Sugar Pill | Negative Symptoms of Schizophrenia - SANS | SANS Total Composite (Week 12) | 5.86 units on a scale | Standard Deviation 5.24 |
| Sugar Pill | Negative Symptoms of Schizophrenia - SANS | SANS Alogia (Week 12) | 0.71 units on a scale | Standard Deviation 1.89 |
| Sugar Pill | Negative Symptoms of Schizophrenia - SANS | SANS Affective Flattening (Week 12) | 1.57 units on a scale | Standard Deviation 3.36 |
| Varenicline | Negative Symptoms of Schizophrenia - SANS | SANS Avolition (Week 12) | 3 units on a scale | Standard Deviation 3.67 |
| Varenicline | Negative Symptoms of Schizophrenia - SANS | SANS Total Global (Week 12) | 3.8 units on a scale | Standard Deviation 2.49 |
| Varenicline | Negative Symptoms of Schizophrenia - SANS | SANS Affective Flattening (Week 12) | 7 units on a scale | Standard Deviation 3.81 |
| Varenicline | Negative Symptoms of Schizophrenia - SANS | SANS Alogia (Week 12) | 0.6 units on a scale | Standard Deviation 1.34 |
| Varenicline | Negative Symptoms of Schizophrenia - SANS | SANS Anhedonia (Week 12) | 5.8 units on a scale | Standard Deviation 7.36 |
| Varenicline | Negative Symptoms of Schizophrenia - SANS | SANS Attention (Week 12) | 0.2 units on a scale | Standard Deviation 0.45 |
| Varenicline | Negative Symptoms of Schizophrenia - SANS | Inappropriate Affect (Week 12) | 0.60 units on a scale | Standard Deviation 0.88 |
| Varenicline | Negative Symptoms of Schizophrenia - SANS | SANS Total Composite (Week 12) | 17.2 units on a scale | Standard Deviation 9.83 |
| Bupropion HCl | Negative Symptoms of Schizophrenia - SANS | SANS Attention (Week 12) | 0 units on a scale | Standard Deviation 0 |
| Bupropion HCl | Negative Symptoms of Schizophrenia - SANS | SANS Alogia (Week 12) | 0 units on a scale | Standard Deviation 0 |
| Bupropion HCl | Negative Symptoms of Schizophrenia - SANS | SANS Total Global (Week 12) | 1.6 units on a scale | Standard Deviation 1.82 |
| Bupropion HCl | Negative Symptoms of Schizophrenia - SANS | Inappropriate Affect (Week 12) | 0.40 units on a scale | Standard Deviation 0.89 |
| Bupropion HCl | Negative Symptoms of Schizophrenia - SANS | SANS Affective Flattening (Week 12) | 0.8 units on a scale | Standard Deviation 1.1 |
| Bupropion HCl | Negative Symptoms of Schizophrenia - SANS | SANS Anhedonia (Week 12) | 1.4 units on a scale | Standard Deviation 3.13 |
| Bupropion HCl | Negative Symptoms of Schizophrenia - SANS | SANS Avolition (Week 12) | 3.6 units on a scale | Standard Deviation 3.78 |
| Bupropion HCl | Negative Symptoms of Schizophrenia - SANS | SANS Total Composite (Week 12) | 6.20 units on a scale | Standard Deviation 5.12 |
Comparison: Statistical analysis for SANS Total Composite (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for SANS Total Global (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for SANS Affective Flattening (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for SANS Alogia (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for SANS Avolition (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for SANS Anhedonia (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for SANS Attention (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis of Inappropriate Affect at Week 12p-value: >0.05ANOVA
Secondary
Positive Symptoms of Schizophrenia (SAPS)
Scale for the Assessment of Positive Symptoms (SAPS), a well-established test, used to assess the presence of psychotic symptoms of schizophrenia. There are 34 items rated on a scale of 0-5 with 0=none and 5=severe for a minimum score of 0 and a maximum score of 170. There are 4 subscales: Hallucinations (minimum score 0; maximum score 35); Delusions (minimum score 0; maximum score 65); Bizarre Behavior (minimum score 0; maximum score 25); Positive Formal Thought Disorder (minimum score 0; maximum score 45). Each subscale contains one additional question as a Global Rating - or overall measure for that particular subscale. The sum of these questions constitutes the Total Global Score (minimum 0, maximum 20). The values for the Global items are included in the Total Composite score. In each case, the higher the score, the greater the severity of symptoms.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Positive Symptoms of Schizophrenia (SAPS) | SAPS Total Composite Score - Week 12 | 3.43 units on a scale | Standard Deviation 4.86 |
| Sugar Pill | Positive Symptoms of Schizophrenia (SAPS) | SAPS Total Global - Week 12 | 1.29 units on a scale | Standard Deviation 1.89 |
| Sugar Pill | Positive Symptoms of Schizophrenia (SAPS) | SAPS Hallucinations - Week 12 | 2 units on a scale | Standard Deviation 3.83 |
| Sugar Pill | Positive Symptoms of Schizophrenia (SAPS) | SAPS Delusions - Week 12 | 1.43 units on a scale | Standard Deviation 1.9 |
| Sugar Pill | Positive Symptoms of Schizophrenia (SAPS) | SAPS Bizarre Behavior - Week 12 | 0 units on a scale | Standard Deviation 0 |
| Sugar Pill | Positive Symptoms of Schizophrenia (SAPS) | SAPS Thought Disorder - Week 12 | 0 units on a scale | Standard Deviation 0 |
| Varenicline | Positive Symptoms of Schizophrenia (SAPS) | SAPS Thought Disorder - Week 12 | 0.6 units on a scale | Standard Deviation 1.34 |
| Varenicline | Positive Symptoms of Schizophrenia (SAPS) | SAPS Total Composite Score - Week 12 | 7 units on a scale | Standard Deviation 7.48 |
| Varenicline | Positive Symptoms of Schizophrenia (SAPS) | SAPS Delusions - Week 12 | 4.2 units on a scale | Standard Deviation 7.36 |
| Varenicline | Positive Symptoms of Schizophrenia (SAPS) | SAPS Bizarre Behavior - Week 12 | 0 units on a scale | Standard Deviation 0 |
| Varenicline | Positive Symptoms of Schizophrenia (SAPS) | SAPS Total Global - Week 12 | 1.2 units on a scale | Standard Deviation 1.3 |
| Varenicline | Positive Symptoms of Schizophrenia (SAPS) | SAPS Hallucinations - Week 12 | 2.2 units on a scale | Standard Deviation 2.59 |
| Bupropion HCl | Positive Symptoms of Schizophrenia (SAPS) | SAPS Total Global - Week 12 | 1.8 units on a scale | Standard Deviation 1.3 |
| Bupropion HCl | Positive Symptoms of Schizophrenia (SAPS) | SAPS Hallucinations - Week 12 | 3 units on a scale | Standard Deviation 4.12 |
| Bupropion HCl | Positive Symptoms of Schizophrenia (SAPS) | SAPS Delusions - Week 12 | 3.8 units on a scale | Standard Deviation 3.56 |
| Bupropion HCl | Positive Symptoms of Schizophrenia (SAPS) | SAPS Thought Disorder - Week 12 | 3.4 units on a scale | Standard Deviation 5.64 |
| Bupropion HCl | Positive Symptoms of Schizophrenia (SAPS) | SAPS Total Composite Score - Week 12 | 10.6 units on a scale | Standard Deviation 7.7 |
| Bupropion HCl | Positive Symptoms of Schizophrenia (SAPS) | SAPS Bizarre Behavior - Week 12 | 0.4 units on a scale | Standard Deviation 0.55 |
Comparison: Statistical analysis for SAPS Total Composite Score - Week 12p-value: >0.05ANOVA
Comparison: Statistical analysis for SAPS Total Global - Week 12p-value: >0.05ANOVA
Comparison: Statistical analysis for SAPS Hallucinations - Week 12p-value: >0.05ANOVA
Comparison: Statistical analysis for Delusions - Week 12p-value: >0.05ANOVA
Comparison: Statistical Analysis for SAPS Bizarre Behavior - Week 12p-value: >0.05ANOVA
Comparison: Statistical analysis for SAPS Thought Disorder - Week 12p-value: >0.05ANOVA
Secondary
Reduction in Smoking
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. Measured at week 12
Time frame: Week 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sugar Pill | Reduction in Smoking | 50% Reduction in Number of Cigarettes Smoked | 2 participants |
| Sugar Pill | Reduction in Smoking | 30% Reduction in Carbon Monoxide (Week 12) | 2 participants |
| Sugar Pill | Reduction in Smoking | 30% Reduction in Serum Cotinine (Week 12) | 2 participants |
| Sugar Pill | Reduction in Smoking | 30% Reduction in Urine Cotinine (Week 12) | 2 participants |
| Varenicline | Reduction in Smoking | 30% Reduction in Urine Cotinine (Week 12) | 4 participants |
| Varenicline | Reduction in Smoking | 50% Reduction in Number of Cigarettes Smoked | 2 participants |
| Varenicline | Reduction in Smoking | 30% Reduction in Serum Cotinine (Week 12) | 4 participants |
| Varenicline | Reduction in Smoking | 30% Reduction in Carbon Monoxide (Week 12) | 2 participants |
| Bupropion HCl | Reduction in Smoking | 30% Reduction in Urine Cotinine (Week 12) | 1 participants |
| Bupropion HCl | Reduction in Smoking | 30% Reduction in Carbon Monoxide (Week 12) | 1 participants |
| Bupropion HCl | Reduction in Smoking | 30% Reduction in Serum Cotinine (Week 12) | 1 participants |
| Bupropion HCl | Reduction in Smoking | 50% Reduction in Number of Cigarettes Smoked | 1 participants |
Comparison: Statistical analysis for 50% Reduction in Number of Cigarettes Smoked (Week 12)p-value: >0.05Chi-squared
Comparison: Statistical Analysis for 30% Reduction in Carbon Monoxide (Week 12)p-value: >0.05Chi-squared
Comparison: Statistical Analysis for 30% Reduction in Serum Cotinine (Week 12)p-value: >0.05Chi-squared
Comparison: Statistical Analysis for 30% Reduction in Urine Cotinine (Week 12)p-value: >0.05Chi-squared
Secondary
Response Style Indicator (Beta) for CPT
Beta represents an individual's response tendency: Some individuals are cautious and choose not to respond very often. Conceptually, such individuals want to make sure they are correct when they give a response. Higher values of Beta reflect this response style. The emphasis is on avoiding commission errors. Other individuals respond more freely to make sure they respond to most or all targets, and they tend to be less concerned about mistakenly responding to a non-target. Lower values of Beta are produced by this response style. Values shown below were obtained at week 12.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugar Pill | Response Style Indicator (Beta) for CPT | 0.95 Beta | Standard Deviation 0.55 |
| Varenicline | Response Style Indicator (Beta) for CPT | 1.41 Beta | Standard Deviation 1.48 |
| Bupropion HCl | Response Style Indicator (Beta) for CPT | 2.92 Beta | Standard Deviation 4.13 |
Comparison: Statistical analysis for Response Style Indicator (Beta) for CPT (week 12)p-value: >0.05ANOVA
Secondary
Side Effects
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. Each item is scored based on a scale of 0=none; 1=mild; 2=moderate; and 3=severe. Below, the data are shown for participants experiencing symptoms on week 12 of the study.
Time frame: Week 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sugar Pill | Side Effects | Anxiety | 3 participants |
| Sugar Pill | Side Effects | Dizziness | 0 participants |
| Sugar Pill | Side Effects | Mania | 0 participants |
| Sugar Pill | Side Effects | Abnormal Dreams | 3 participants |
| Sugar Pill | Side Effects | Abdominal Pain | 0 participants |
| Sugar Pill | Side Effects | Headache | 3 participants |
| Sugar Pill | Side Effects | Insomnia | 1 participants |
| Sugar Pill | Side Effects | Irregular Heart Beat | 0 participants |
| Sugar Pill | Side Effects | Weakness/Fainting | 2 participants |
| Sugar Pill | Side Effects | Diarrhea | 1 participants |
| Sugar Pill | Side Effects | Vomiting | 0 participants |
| Sugar Pill | Side Effects | Constipation | 0 participants |
| Sugar Pill | Side Effects | Irritability | 1 participants |
| Sugar Pill | Side Effects | Drooling | 0 participants |
| Sugar Pill | Side Effects | Leg Pain/Cramps | 2 participants |
| Sugar Pill | Side Effects | Psychosis | 0 participants |
| Sugar Pill | Side Effects | Dry Mouth | 2 participants |
| Sugar Pill | Side Effects | Nausea | 0 participants |
| Sugar Pill | Side Effects | Chest Pain | 0 participants |
| Sugar Pill | Side Effects | Confusion | 0 participants |
| Sugar Pill | Side Effects | Cold Sweats | 0 participants |
| Sugar Pill | Side Effects | Blurred Vision | 0 participants |
| Varenicline | Side Effects | Cold Sweats | 0 participants |
| Varenicline | Side Effects | Anxiety | 3 participants |
| Varenicline | Side Effects | Vomiting | 0 participants |
| Varenicline | Side Effects | Dry Mouth | 0 participants |
| Varenicline | Side Effects | Dizziness | 0 participants |
| Varenicline | Side Effects | Drooling | 1 participants |
| Varenicline | Side Effects | Abnormal Dreams | 1 participants |
| Varenicline | Side Effects | Mania | 0 participants |
| Varenicline | Side Effects | Diarrhea | 1 participants |
| Varenicline | Side Effects | Confusion | 1 participants |
| Varenicline | Side Effects | Insomnia | 0 participants |
| Varenicline | Side Effects | Abdominal Pain | 1 participants |
| Varenicline | Side Effects | Leg Pain/Cramps | 1 participants |
| Varenicline | Side Effects | Constipation | 1 participants |
| Varenicline | Side Effects | Headache | 3 participants |
| Varenicline | Side Effects | Weakness/Fainting | 0 participants |
| Varenicline | Side Effects | Blurred Vision | 1 participants |
| Varenicline | Side Effects | Chest Pain | 0 participants |
| Varenicline | Side Effects | Psychosis | 0 participants |
| Varenicline | Side Effects | Nausea | 2 participants |
| Varenicline | Side Effects | Irregular Heart Beat | 0 participants |
| Varenicline | Side Effects | Irritability | 0 participants |
| Bupropion HCl | Side Effects | Dizziness | 1 participants |
| Bupropion HCl | Side Effects | Weakness/Fainting | 1 participants |
| Bupropion HCl | Side Effects | Dry Mouth | 0 participants |
| Bupropion HCl | Side Effects | Diarrhea | 0 participants |
| Bupropion HCl | Side Effects | Vomiting | 0 participants |
| Bupropion HCl | Side Effects | Constipation | 1 participants |
| Bupropion HCl | Side Effects | Irritability | 1 participants |
| Bupropion HCl | Side Effects | Cold Sweats | 0 participants |
| Bupropion HCl | Side Effects | Blurred Vision | 1 participants |
| Bupropion HCl | Side Effects | Leg Pain/Cramps | 0 participants |
| Bupropion HCl | Side Effects | Confusion | 1 participants |
| Bupropion HCl | Side Effects | Psychosis | 1 participants |
| Bupropion HCl | Side Effects | Drooling | 1 participants |
| Bupropion HCl | Side Effects | Anxiety | 0 participants |
| Bupropion HCl | Side Effects | Nausea | 1 participants |
| Bupropion HCl | Side Effects | Mania | 0 participants |
| Bupropion HCl | Side Effects | Abnormal Dreams | 0 participants |
| Bupropion HCl | Side Effects | Abdominal Pain | 1 participants |
| Bupropion HCl | Side Effects | Insomnia | 1 participants |
| Bupropion HCl | Side Effects | Headache | 0 participants |
| Bupropion HCl | Side Effects | Chest Pain | 0 participants |
| Bupropion HCl | Side Effects | Irregular Heart Beat | 0 participants |
Comparison: Statistical analysis for Anxiety at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Dizziness at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Mania at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for abnormal dreams at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Abdominal Pain at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Headache at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Insomnia at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Nausea at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Psychosis at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Dry Mouth at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Chest Pain at Week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Irregular Heart Beat at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Weakness/Fainting at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Diarrhea at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Vomiting at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Constipation at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Confusion at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Irritability at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for drooling at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Cold Sweats at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Blurred Vision at week 12p-value: >0.05Fisher Exact
Comparison: Statistical analysis for Leg Pain/Crampsp-value: >0.05Fisher Exact
Secondary
Suicidality
The Columbia-Suicide Severity Rating Scale (C-SSRS), is a survey intended to quantify the severity of suicidal ideation and behavior. The questionaire for suicidal ideation consists of 5 questions with yes (1) /no (0) answers. If answers to questions 1 and 2 are no, questions 3-5 are skipped. Minimum of 0; Maximum of 5. The questionaire for suicidal behavior consists of seven questions rated 0 for no and 1 for yes. The minimum score is 0 and the maximum score is 7. In each case, the higher the score, the greater the severity.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Suicidality | Lifetime Suicidal Ideation (week 12) | 1.71 units on a scale | Standard Deviation 1.7 |
| Sugar Pill | Suicidality | Lifetime Suicide Attempts (week 12) | 1.29 units on a scale | Standard Deviation 1.7 |
| Varenicline | Suicidality | Lifetime Suicidal Ideation (week 12) | 0.8 units on a scale | Standard Deviation 0.84 |
| Varenicline | Suicidality | Lifetime Suicide Attempts (week 12) | 1.2 units on a scale | Standard Deviation 1.3 |
| Bupropion HCl | Suicidality | Lifetime Suicidal Ideation (week 12) | 0.4 units on a scale | Standard Deviation 0.55 |
| Bupropion HCl | Suicidality | Lifetime Suicide Attempts (week 12) | 0.4 units on a scale | Standard Deviation 0.55 |
Comparison: Statistical analysis for Lifetime Suicidal Ideation (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for Lifetime Suicide Attempts (Week 12)p-value: >0.05ANOVA
Secondary
Urge to Smoke - MNWS
The Minnesota Nicotine Withdrawal Scale (MNWS) includes two items where individuals are asked to 1) declare the percentage of time they had an urge to smoke (MNWS % Urge to Smoke); and 2) declare the percentage of time they had a strong urge to smoke (MNWS % Strong Urge). For each case, percentages range from 0% to 100% - the higher the percentage, the greater urge to smoke.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Urge to Smoke - MNWS | MNWS % Urge to Smoke (Week 12) | 36.43 percentage of time | Standard Deviation 18.87 |
| Sugar Pill | Urge to Smoke - MNWS | MNWS % Strong Urge (Week 12) | 26.43 percentage of time | Standard Deviation 23.4 |
| Varenicline | Urge to Smoke - MNWS | MNWS % Urge to Smoke (Week 12) | 47 percentage of time | Standard Deviation 22.8 |
| Varenicline | Urge to Smoke - MNWS | MNWS % Strong Urge (Week 12) | 33 percentage of time | Standard Deviation 18.57 |
| Bupropion HCl | Urge to Smoke - MNWS | MNWS % Urge to Smoke (Week 12) | 47 percentage of time | Standard Deviation 34.21 |
| Bupropion HCl | Urge to Smoke - MNWS | MNWS % Strong Urge (Week 12) | 32.4 percentage of time | Standard Deviation 40.61 |
Comparison: Statistical analysis for MNWS % Urge to Smoke (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for MNWS % Strong Urge (Week 12)p-value: >0.05ANOVA
Secondary
Variability of Standard Error - CPT
Variability of Standard Error (VSE) is a measure of response speed consistency. VSE measures within respondent variability. That is, the amount of variability the individual shows in 18 separate segments of the Continuous Performance Test in relation to his or her own overall standard error. Although VSE is a different measure than Overall Standard Error, typically the two measures produce comparable results. The higher the VSE, the greater the inconsistency in the response speed. The values shown below are the VSE for Week 12.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugar Pill | Variability of Standard Error - CPT | 11.05 milliseconds | Standard Deviation 10.99 |
| Varenicline | Variability of Standard Error - CPT | 11.38 milliseconds | Standard Deviation 6.84 |
| Bupropion HCl | Variability of Standard Error - CPT | 11.8 milliseconds | Standard Deviation 6.01 |
Comparison: Statistical analysis for Variability of Standard Error - CPT (Week 12)p-value: >0.05ANOVA
Secondary
Vital Signs
blood pressure will be measured.
Time frame: Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sugar Pill | Vital Signs | Systolic Blood Pressure (Week 12) | 116.29 mm Hg | Standard Deviation 15.53 |
| Sugar Pill | Vital Signs | Diastolic Blood Pressure (Week 12) | 76.71 mm Hg | Standard Deviation 9.94 |
| Varenicline | Vital Signs | Systolic Blood Pressure (Week 12) | 122 mm Hg | Standard Deviation 7.34 |
| Varenicline | Vital Signs | Diastolic Blood Pressure (Week 12) | 78.4 mm Hg | Standard Deviation 8.14 |
| Bupropion HCl | Vital Signs | Systolic Blood Pressure (Week 12) | 128.4 mm Hg | Standard Deviation 32.42 |
| Bupropion HCl | Vital Signs | Diastolic Blood Pressure (Week 12) | 74.8 mm Hg | Standard Deviation 10.71 |
Comparison: Statistical analysis for systolic blood pressure (Week 12)p-value: >0.05ANOVA
Comparison: Statistical analysis for diastolic blood pressure (Week 12)p-value: >0.05ANOVA
Secondary
Vital Signs - Pulse
Pulse will be measured. The values below were measured at week 12 of the study.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugar Pill | Vital Signs - Pulse | 82.57 heart beats per minute | Standard Deviation 15.76 |
| Varenicline | Vital Signs - Pulse | 87 heart beats per minute | Standard Deviation 13.43 |
| Bupropion HCl | Vital Signs - Pulse | 89.2 heart beats per minute | Standard Deviation 18.47 |
Comparison: Statistical analysis for Vital Signs - Pulse (Week 12)p-value: >0.05ANOVA
Secondary
Vital Signs - Weight
Weight will be measured for each participant. Values listed below are for week 12.
Time frame: Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sugar Pill | Vital Signs - Weight | 218.39 lbs | Standard Deviation 69.64 |
| Varenicline | Vital Signs - Weight | 213.47 lbs | Standard Deviation 35.2 |
| Bupropion HCl | Vital Signs - Weight | 254.78 lbs | Standard Deviation 65.5 |
Comparison: Statistical analysis for Vital Signs - Weight (Week 12)p-value: >0.05ANOVA