college of problems of drug dependence, june 14, 2010 scottsdale, az
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Modafinil on Smoking Cessation: A Clinical Trial. College of Problems of Drug Dependence, June 14, 2010 Scottsdale, AZ. Catherine Martin, G Guenthner, K House, B Beck R Charnigo , T Kelly Departments of Psychiatry and Behavioral Science - PowerPoint PPT PresentationTRANSCRIPT
College of Problems of Drug Dependence,
June 14, 2010 Scottsdale, AZ
Modafinil on Smoking Cessation:
A Clinical Trial
Catherine Martin, G Guenthner, K House, B Beck R Charnigo, T Kelly
Departments of Psychiatry and Behavioral Science
College of Medicine and College of Public Health
University of Kentucky
Funded
NIDAR21DA023049P50 DA05312
CephalonStudy Drug and Data
Entry
Scope of the Problem
Smoking is the single most preventable cause of premature death and disease in the U.S. (CDC, 2009)
Modafinil
◘ FDA approved for use in narcolepsy, shift-work sleep disorder and obstructive sleep apnea with excessive sleepiness
◘ Peak plasma concentrations are at 2-3 hours
◘ Half-life is 14-17 hours◘ Usual dose is 200 mg
Modafinil
◘ Mechanism of action is not clear but appears to be related to:▪ GABA and glutamate levels▪ Noradrenergic (including
dopaminergic), serotonergic, histaminergic and adrenergic systems must be intact
▪ Orexin role is controversial ▪ For a review see Kumar 2008
Modafinil as Treatment
◘ Cocaine dependence, Dackis et al., 2005; Andersib et al., 2009
◘ Methamphetamine dependence in a subset of abusers, Heinzerling et al., 2010
◘ Nicotine dependence: with 200 mg saw less decrease in smoking behaviors than controls, Schnoll et al., 2008
Modafinil for smoking cessation: possible mechanism
Impacts on symptoms associated with smoking and possible symptoms of nicotine withdrawal, including:
depression (Price and Taylor, 2005)
ADHD (Amiri et al, 2008)
weight concerns (Makris et al., 2004); we observed decreases in VAS hungry in a Phase I clinic trial investigating the combination of modafinil and nicotine (Martin et al., 2006)
Clinical Trial:Inclusion and exclusion
criteriaInclusion: medically stable individuals between 18 and 55 a CO of >10 ppm self-report smoking >10 cigarettes
Exclusion:regular use of drugs of abuse current use of psychiatric medicationspregnancy or unwillingness to use non-steroidal birth control current and regular use of nicotine through routes other than tobacco smoking
Modafinil Dose and Stratification
initially were randomized to 200 mg if < 200 lbs and 300 mg if > 200 pounds
after communication with Dr. Schnoll (via Dr. Childress), subjects were randomized to placebo or 300 mg
stratified by gender and smoking level (low: 10-19 cigarettes/day and high: > 20 cigarettes/day)
for this first analysis, we examined those subjects randomized to 300 mg of modafinil or placebo
Subjects
168 clinical screens 72 received drug 50 maintained on the 8 week active drug
phase•34 females (8 African American; 26 white)•16 males (1 African American; 15 white)
8 randomized to 200 mg 42 randomized to placebo or 300 mg
Baseline
Drug
Week 1: Day 1 (Quit Day); Day 2; Day 7
Week 2
Week 3
Week 4
Week 5
Week 6
Week 7
Week 8
Follow-up
Week 9
Week 20
Eight-week intervention and follow-up
Assessments
Cigarette Smoking Medical Monitoring•Timeline Followback •Vital Signs
•CO •BMI
•Cotinine •Weight
Measures of Drug Effects
•Pregnancy Tests
•Medication Side Effects
•Urine Drug Screens
•CPT •Alcohol BAC
•VAS •Beck Depression Inventory
•ARCI •CAARS
Nicotine Withdrawal•Fagerstrom
•QSU
Tob
acco
Con
sum
ptio
n
0.0
2.5
5.0
7.5
10.0
12.5
15.0
17.5
20.0
Time
-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5
Tobacco Consumption Trajectories
PLOT Placebo Modafinil
TTimeline Followback
Modafinil Side Effects p < .05
Hea
rt R
ate
75.0
77.5
80.0
82.5
85.0
87.5
90.0
92.5
95.0
Time
-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5
Heart Rate Trajectories
PLOT Placebo Modafinil
Dia
stol
ic B
lood
Pre
ssur
e
70.0
72.5
75.0
77.5
80.0
82.5
85.0
87.5
90.0
Time
-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5
Diastolic Blood Pressure Trajectories
PLOT Placebo Modafinil
Syst
olic
Blo
od P
ress
ure
115.0
117.5
120.0
122.5
125.0
127.5
130.0
132.5
135.0
Time
-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5
Systolic Blood Pressure Trajectories
PLOT Placebo Modafinil
Con
cent
rati
on
3
4
5
6
7
8
9
Time
-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5
Concentration Trajectories
PLOT Placebo Modafinil
VAS: Concentrate
Summary of Modafinil and Smoking Cessation
Based on self-report decreased smoking decreased appetite increased concentration
No evidence of increased smoking relative to placebo
Side effects were observed, including increased heart rate and blood pressure increased heart rate was clinically significant one
time
Modafinil may have a role to play in smoking cessation, especially in special populations