Assessing Neuropsychiatric Symptoms Including Depression, Anxiety, Irritability, and Suicidal Thoughts or Behavior in Subjects Quitting Smoking on Varenicline Tartrate or Placebo

POMS TMD were responses to 65 items in 6 subscales (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor, Fatigue, and Confusion), on 'How you feel right now?' (scale:0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely). All items were rated in the same direction except for Relaxed and Efficient in the Tension-Anxiety and Confusion subscales. TMD was the sum of the scores of all 6 subscales but weighting Vigor negatively. Summary results (TMD scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

POMS Tension-Anxiety subscale data were responses to 9 items regarding 'How you feel right now?' on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. All items were rated in the same direction except for Relaxed. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

POMS Depression-Dejection subscale data responses to 15 items regarding 'How you feel right now?' on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

POMS Anger-Hostility subscale data were responses to 12 items regarding 'How you feel right now?' on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

POMS Vigor subscale data were responses to 8 items regarding 'How you feel right now?' on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

POMS Fatigue subscale data were responses to 7 items regarding 'How you feel right now?' on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. All items were rated in the same direction. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

POMS Confusion subscale data were responses to 7 items regarding 'How you feel right now?' on a scale of 0=not at all, 1=a little, 2=moderately, 3=quite a bit, and 4=extremely. All items were rated in the same direction except for Efficient. Summary results (subscale scores) were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance).

The MADRS measures the overall severity of depressive symptoms and is a 10-item checklist. Each item was rated on a scale of 0 to 6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

HAM-A measures treatment-related changes in generalized anxiety symptoms and is a 14-item questionnaire. Each item was scored from 0 (not present) to 4 (very severe) and a lower score indicated less affected. Total scores ranged from 0 (not affected) to 56 (very severely affected).

The OAS-m contains 3 scales: Aggression (Questions [Q]1 to 4), Irritability (Q5 to 6), and Suicidality (Q7 to 7b). Aggression total score was calculated by summing the weighted scores in Q1 to 4. Scores for each question ranged from 0 (no events) to 5 (very severe events). Total scores ranged from 0 (no aggression) to any number with no upper limit depending on the frequency of agressive behaviour in a week.

The OAS-m contains 3 scales: Aggression (Questions [Q]1 to 4), Irritability (Q5 to 6), and Suicidality (Q7 to 7b). Irritability total score was calculated by summing the items in Q5 to 6. Scores for each question ranged from 0 (not at all) to 5 (extreme). Total scores ranged from 0 (no irritability) to 10 (extreme irritability).

The OAS-m contains 3 scales: Aggression (Questions [Q]1 to 4), Irritability (Q5 to 6), and Suicidality (Q7 to 7b). Suicidality total score was calculated by summing the items Q7 to 7b. Scores for Q7 ranged from 0 (none) to 6 (very extreme) and scores for Q7a to 7b ranged from 0 (none) to 5 (extreme). Total scores ranged from 0 (no suicidal tendency) to 16 (extreme/very extreme suicidal tendency).

The SDAS contains 11 items with 5 possible responses: 0=not present, 1=doubtful or very mild, 2=mild to moderate, 3=severe, and 4=extremely severe. The SDAS was collected 3 times a day during the inpatient abstinence period (BC). Total scores ranged from 0 (not present) to 44 (extremely severe).

The BIS-11 is a 30-item self-report questionnaire designed to assess general impulsiveness taking into account the multifactorial nature of the construct. Possible responses to each item were: 1=rarely/never, 2=occasionally, 3=often, and 4=almost always/always. Scores of Items 1, 7, 8, 9, 10, 12, 13, 15, 20, 29 and 30 were reversed when calculating the total score. Total score ranged from 30 (less impulsive) to 120 (more impulsive).

The MNWS total score contains 9 items (urge to smoke; depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating; restlessness; increased appetite; difficulty going to sleep; difficulty staying asleep). Each item was rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Total scores were the average score for all 9 items and ranged from 0 (no withdrawal symptoms) to 4 (extreme withdrawal symptoms).

The MNWS negative affect domain subscale contains 4 items (depressed mood; irritability, frustration, or anger; anxiety; difficulty concentrating). Each item was rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores were the average from all 4 items and ranged from 0 (no negative affect) to 4 (extreme negative affect).

The MNWS insomnia domain subscale contains 2 items (difficulty going to sleep; difficulty staying asleep). Each item was rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores were the average of the 2 items and ranged from 0 (no insomnia) to 4 (extreme insomnia).

The MNWS urge to smoke subscale contains 1 item (urge to smoke) rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores ranged from 0 (no urge to smoke) to 4 (extreme urge to smoke).

The MNWS restlessness subscale contains 1 item (restlessness) rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores ranged from 0 (no restlessness) to 4 (extreme restlessness).

The MNWS increased appetite subscale contains 1 item (increased appetite) rated from 0 to 4 where 0=not at all, 1=slight, 2=moderate, 3=quite a bit, and 4=extreme. Scores ranged from 0 (no increased appetite) to 4 (extreme increased appetite).

POMS total mood disturbance (TMD) summary results were presented as transformed T-scores ranging from 30 (less disturbance) to 80 (more disturbance). Participants exceeding the threshold had an increase from baseline of 1 standard deviation of the TMD baseline T-score plus 1 or more.

The MADRS measures the overall severity of depressive symptoms. Total score ranged from 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Participants exceeding the threshold had a MADRS total score of more than 14 out of 60. MADRS total scores exceeding 14 may represent clinically notable effective symptomatology.

HAM-A measures treatment-related changes in generalized anxiety symptoms. Total scores ranged from 0 (not affected) to 56 (very severely affected). Participants exceeding the threshold had a HAM-A total score of more than or equal to 14 out of 56. HAM-A total scores of more than or equal to 14 may reflect clinically noteworthy levels of anxiety.

The OAS-m contains 3 scales: Aggression, Irritability, and Suicidality. Aggression total score ranged from 0 (no aggression) to any number with no upper limit depending on the frequency of agressive behaviour in a week. Participants exceeding the threshold had an OAS-m Aggression total score of more than or equal to 3 out of any number with no upper limit depending on the frequency of agressive behaviour in a week. OAS-m Aggression total scores of more than or equal to 3 reflect clinically important aggression.

The OAS-m contains 3 scales: Aggression, Irritability, and Suicidality. Irritability total score ranged from 0 (no irritability) to 10 (extreme irritability). Participants exceeding the threshold had an OAS-m Irritability total score of more than or equal to 2 out of 10. OAS-m Irritability total scores of more than or equal to 2 reflect clinically important irritability.

The OAS-m contains 3 scales: Aggression, Irritability, and Suicidality. Suicidality total score ranged from 0 (no suicidal tendency) to 16 (extreme/very extreme suicidal tendency). No threshold criterion was determined for OAS-m Suicidality total score.

The BIS-11 is designed to assess general impulsiveness taking into account the multifactorial nature of the construct. Total score ranged from 30 (less impulsive) to 120 (more impulsive). Participants exceeding the threshold had a BIS-11 total score more than or equal to 70 out of 120. BIS-11 total scores of more than or equal to 70 could reflect clinically important and potentially pathological impulsivity.

SDAS total scores ranged from 0 (not present) to 44 (extremely severe). Participants exceeding the threshold had a SDAS total score of more than 6 out of 44.

Participants who reported no smoking and no use of other nicotine-containing products since the last study visit (on the Nicotine Use Inventory, which was used to collect the information of cigarette or other nicotine use during the study) and who did not have carbon monoxide of more than 10 parts per million at any time from Week 9 to Week 12

Participants who reported no smoking and no use of other nicotine-containing products since the last study visit (during treatment) in the previous 7 days and who did not have carbon monoxide of more than 10 parts per million for that observation (if measured).