Fig 1.
Flow chart of disposition of patients through the study.
Number of patients who were used for each major outcome measures in main analysis: Cognition: MATRICS battery Composite Score N = 54, Varenicline = 25, Placebo = 29; for number of subjects analyzed for individual Domain scores on MATRICS see Table 3 and Fig 3. Smoking Measures-Cigarettes Smoked and Breathalyzer CO N = 87, Varenicline = 42, Placebo = 45; Nicotine and Cotinine N = 70, Varenicline = 34, Placebo = 36; Smoking Urges QSU N = 85, varenicline = 40, Placebo = 45; Psychopathology Measures—PANSS Scale N = 77, Varenicline = 38, Placebo = 39; SANS Scale n = 64, Varenicline = 30, Placebo = 34; Calgary Depression Scale N = 74, Varenicline = 36, Placebo = 38.
Table 1.
Subject characteristics in varenicline and placebo groups.
N = 87 (varenicline N = 42, placebo N = 45) based on subjects who had one post baseline reading on at least one outcome variable. Actual N's for some variables are lower because of missing data on selected subjects.
Fig 2.
Effects of varenicline and placebo on measures related to cigarette smoking.
Each value represents model adjusted least square mean score ± s.e.m. for that week, from mixed model ANCOVA. Significance of difference between varenicline and placebo means at specific time point (t-test): * P < .05, **, P < .01, *** P < .001. For Cigarette and CO values, statistics were calculated from analyses using square-root transformed values, which better approximated a normal distribution. Overall Drug Effect from mixed model ANCOVA: (A) Cigarettes Smoked/Day (N = 87, Varenicline = 42, Placebo = 45) Drug Effect F = 14.88, DF = 1, 81, P = 0.0002; Drug x Time Effect: F = 1.67, DF = 8,532, P = 0.1035. (B) C0 (N = 87, Varenicline = 42, Placebo = 45) Drug Effect: F = 16.27, DF = 1,81, P = 0.0001; Drug x Time Effect: F = 2.08 DF = 8,535, P = 0.0357; (C) Cotinine (N = 70, varenicline = 34, Placebo = 36) Drug Effect: F = 16.30, DF = 1,64, P = 0.0001; Drug X Time Effect: F = 8.81, DF = 2,112, P = .00003,; (D) Smoking Urges (QSU) (N = 85, varenicline = 40, Placebo = 45) Drug Effect: F = 7.20, DF = 1,79, P = 0.0089; Drug X Time Effect: F = 0.86, DF = 8,518, P = 0.5502.
Table 2.
Change from baseline in smoking related measures at selected weeks of treatment after baseline.
Each value represents mean ± s.e.m. of model estimated difference score (wki-baseline). Difference of mean difference from 0 (no change) for measure for each drug group at specific time point:
Table 3.
Change from baseline in MATRICS Battery Scores by week 8 of drug treatment.
Each value represents mean ± s.e.m of model estimated difference score (wk8-baseline). Difference of mean difference from 0 (i.e., no change) for measure for each drug group at specific time point:
Fig 3.
Comparison of MATRICS Battery Domain and Overall Composite Scores In varenicline- and placebo- treated patients.
N's are shown in figure. Each value represents mean ± s.e.m. of Domain or Composite scores of subjects who had complete values on all Domain scores at baseline and week 8. Mean scores are not adjusted for baseline covariate value or site effects. Abbreviations of Domain and Composite scores in figure: SP = speed of processing, AV = attention-vigilance, WM = working memory, VERBL = verbal learning, VISL = visual learning, RP = reasoning-problem solving, COMP = overall composite. Significance of difference for specific Domain or Composite score between baseline and 8 week value: *P < .05, by paired t-test.
Table 4.
Change from baseline in psychiatric symptoms scores with varenicline or placebo.
Each value represents mean ± s.e.m. of model estimated difference score (wki-baseline). SANS Modified Total = Sum of scores of Affective Flattering, Alogia, Avolition, Anhedonia. PANSS Depression is sum of scores from items G2+G3+G6 (adopted from Lancon [58]. F represents results of analysis of covariance, with baseline scores as covariate. PANSS and Calgary Depression scores used SAS Mixed Model with difference scores from week 4 and week 8 and baseline score as covariate. SANS was analyzed by SPSS Univariate ANCOVA GLM of week 8-baseline difference score with baseline score as covariate. Statistical significance of mean difference from 0 (i.e., no change) for measure for each drug group at specific time point:
Fig 4.
Effect of varenicline and placebo on PANSS Total and Depression Scores.
N = 77, Varenicline = 38, Placebo = 39. Each value represents model adjusted least square mean score ± s.e.m. for that week, from mixed model ANCOVA. Overall Drug Effect between varenicline and placebo: PANSS Total F = 2.11, DF = 1, 71, P = 0.151; PANSS Depression Factor F = 4.79, df = 1,71, P = 0.032. Significance of difference from same drug baseline in varenicline treated patients by least square means t-test: * P<0.05, **P<0.01.