dependency By Darush Attar-Zadeh BPharm MFRPSII - - PowerPoint PPT Presentation
Therapeutic options to reduce tobacco dependency By Darush Attar-Zadeh BPharm MFRPSII darushattar@hotmail.com Need to have the right resources available at
By Darush Attar-Zadeh BPharm MFRPSII darushattar@hotmail.com
available at http://www.londonsenate.nhs.uk/wp-content/uploads/2015/04/The-expired-carbon-monoxide-CO-test-guidance-for-health- professionals.pdf
1. Russell MAH, et al. BMJ 1976; 1:1043-1046 2. Nicotine addiction in Britain: A report of the Tobacco Advisory Group of the Royal college of Physcians. London: Royal College of Physicians, 2000
(EVALUATING ADVERSE EVENTS IN A GLOBAL SMOKING CESSATION STUDY)
Partial agonist
receptor, only partially stimulating dopamine release1
withdrawal symptoms1-3
Antagonist
by nicotine
full relapse after a temporary lapse1-4
Varenicline at the 42 receptor
8144 smokers 4028 non-psych; 4116 psych 16 countries, 6 continents 30th Nov 2011- 13th Jan 2015 2037 varenicline 2034 bupropion 2038 NRT 2035 placebo
6
exhaled carbon monoxide (CO) of >10 ppm at screening
Disorders) to have either: No current or past psychiatric diagnosis (50% of subjects) OR One or more clinically stable current or past diagnosis of (50% of subjects):
Psychotic disorder – schizophrenia, schizoaffective disorder Affective disorder – major depression, bipolar I, bipolar II Anxiety disorder – panic disorder with or without agoraphobia, post- traumatic stress disorder, obsessive-compulsive disorder, social phobia, generalised anxiety disorder Personality disorder – limited to past history of borderline personality disorder
Subjects with psychiatric diagnoses must be clinically stable:
No acute exacerbation in the preceding 6 months If on treatment, stable drug and dose for ≥3 months
efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016 Apr 22. doi: 10.1016/S0140-6736(16)30272-0 [Epub ahead of print]
months
treatment with any of the active drugs in the study, and that is of sufficient concern that further exposure to this medication would be inadvisable
Severity (CGI-S)
efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016 Apr 22. doi: 10.1016/S0140-6736(16)30272-0 [Epub ahead of print]
Primary Safety Endpoint: The percentage of subjects reporting at least one of the following Neuropsychiatric (NPS) adverse events (AEs) during treatment and up to 30 days after last dose: Main Efficacy Measure: CO-confirmed 4-week continuous abstinence rates (CAR) for Weeks 9-12
Anxiety Depression Feeling abnormal Hostility Agitation Panic Aggression Paranoia Delusions Psychosis Hallucinations Suicidal ideation Homicidal ideation Suicidal behaviour Mania Completed suicide
Classified as Moderate
Severe Classified as Severe
efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016 Apr 22. doi: 10.1016/S0140-6736(16)30272-0 [Epub ahead of print] Adverse events were rated by trained investigators as mild (no interference with participant’s usual daily functioning), moderate (some interference with functioning), or severe (substantial interference). Prespecified severity criteria for the primary neuropsychiatric adverse event endpoint required adverse events for the four components expected to be reported more commonly (anxiety, depression, feeling abnormal, or hostility) to be rated as severe. Neuropsychiatric adverse events in the remaining 12 categories (agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, behaviour, or completed suicide) met severity criteria when rated as either moderate or severe.
Cohort Participants with Events n/N, % Varenicline Bupropion NRT Patch Placebo
Non-Psychiatric 13/990 1.3% 22/989 2.2% 25/1006 2.5% 24/999 2.4% Psychiatric 67/1026 6.5% 68/1017 6.7% 53/1016 5.2%* 50/1015 4.9% Moderate to severe neuropsychiatric AEs reported during treatment and ≤30 days after last dose. In a general linear model analysis pre-specified in the protocol, there was a significant treatment-by-cohort interaction. Therefore statistical analyses of the NPS AE endpoint by treatment assignment were conducted for each cohort separately.
efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016 Apr 22. doi: 10.1016/S0140-6736(16)30272-0 [Epub ahead of print] *One additional participant in the nicotine patch group (psychiatric cohort) who reported moderate suicidal ideation (serious adverse events) was identified after the clinical database was locked; consequently, the participant was not included in the analysis of the primary study endpoint.
Secondary Outcome Measure Varenicline Bupropion NRT Patch Placebo Non-Psychiatric Cohort, N 990 989 1006 999 NPS AE Endpoint, n (%) 13 (1.3%) 22 (2.2%) 25 (2.5%) 24 (2.4%) Severe only 1 (0.1%) 4 (0.4%) 3 (0.3%) 5 (0.5%) Psychiatric Cohort, N 1026 1017 1016 1015 NPS AE Endpoint, n (%) 67 (6.5%) 68 (6.7%) 53 (5.2%)* 50 (4.9%) Severe only 14 (1.4%) 14 (1.4%) 14 (1.4%) 13 (1.3%)
efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016 Apr 22. doi: 10.1016/S0140-6736(16)30272-0 [Epub ahead of print] Adverse events were rated by trained investigators as mild (no interference with participant’s usual daily functioning), moderate (some interference with functioning), or severe (substantial interference). Prespecified severity criteria for the primary neuropsychiatric adverse event endpoint required adverse events for the four components expected to be reported more commonly (anxiety, depression, feeling abnormal, or hostility) to be rated as severe. Neuropsychiatric adverse events in the remaining 12 categories (agitation, aggression, delusions, hallucinations, homicidal ideation, mania, panic, paranoia, psychosis, suicidal ideation, behaviour, or completed suicide) met severity criteria when rated as either moderate or severe. *One additional participant in the nicotine patch group (psychiatric cohort) who reported moderate suicidal ideation (serious adverse events) was identified after the clinical database was locked; consequently, the participant was not included in the analysis of the primary study endpoint.
Odds Ratios CAR Weeks 9-12 Main Efficacy Measure OR (95% CI) P value Varenicline vs. placebo* 3.24 (2.56, 4.11) P<0.0001 Bupropion vs. placebo* 1.87 (1.46, 2.39) P<0.0001 NRT vs. placebo 2.00 (1.56, 2.55) P<0.0001 Varenicline vs. NRT 1.62 (1.32, 1.99) P<0.0001 Bupropion vs. NRT 0.94 (0.75, 1.16) P=0.5467 Varenicline vs. bupropion 1.74 (1.41, 2.14) P<0.0001
efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016 Apr 22. doi: 10.1016/S0140-6736(16)30272-0 [Epub ahead of print]
29.2 19.3 20.4 11.4
5 10 15 20 25 30 35 Weeks 9–12
Varenicline (n=1032) Bupropion (n=1033) NRT (n=1025) Placebo (n=1026)
Adapted from Anthenelli, 2016
Continuous Abstinence Rate (%)
*Primary comparisons
OR = Odds Ratio, CI = Confidence Interval
Odds Ratios CAR Weeks 9-24 OR (95% CI) P value Varenicline vs. placebo* 2.50 (1.90, 3.29) P<0.0001 Bupropion vs. placebo* 1.77 (1.33, 2.36) P<0.0001 NRT vs. placebo 1.65 (1.24, 2.20) P=0.0007 Varenicline vs. NRT 1.51 (1.19, 1.93) P=0.0008 Bupropion vs. NRT 1.07 (0.83, 1.39) P=0.5824 Varenicline vs. bupropion 1.41 (1.11, 1.79) P=0.0047
efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet 2016 Apr 22. doi: 10.1016/S0140-6736(16)30272-0 [Epub ahead of print]
Continuous Abstinence Rate (%)
Adapted from Anthenelli, 2016
18.3 13.7 13.0 8.3
2 4 6 8 10 12 14 16 18 20 Weeks 9–24
Varenicline (n=1032) Bupropion (n=1033) NRT (n=1025) Placebo (n=1026)
*Primary comparisons
OR = Odds Ratio, CI = Confidence Interval
15
Reference: www.londonsenate.nhs.uk/helping-smokers-quit/ [Accessed September 2016]
https://www.youtube.com/channel/UClzwyrg7 Wv3LxObo9R1fV9A http://www.ncsct.co.uk/pu blication_electronic_cigar ette_briefing.php http://ash.org.uk/files/docu ments/ASH_715.pdf (ASH also updates its briefings) It’s the Tar that kills, not the Nicotine We’re a stop smoking service, not a stop nicotine service
1st generation 2nd generation 3rd generation
By Darush Attar-Zadeh BPharm MFRPSII darushattar@hotmail.com