• Seven-day point prevalence smoking abstinence at end of trial (abstinence based on self-reported smoking abstinence verified by CO levels < 10 ppm) [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  

• Last four weeks of Trial Continuous smoking abstinence rates (verified by CO < 10 ppm) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  
• Seven-day point prevalence smoking abstinence [ Time Frame: end of treatment, six-month follow-up ] [ Designated as safety issue: No ]
  
• Treatment retention (based on survival analysis and number of weeks a subject completes in the trial) [ Time Frame: upon completion ] [ Designated as safety issue: No ]
  
• Time line follow back for cigarettes smoked, alcohol and caffeinated beverage use [ Time Frame: Weeks 1-8; six-month follow-up ] [ Designated as safety issue: No ]
  
• Tobacco craving as assessed by Tiffany scale for smoking urges [ Time Frame: Weeks 1, 4 and 8; 6-month follow-up ] [ Designated as safety issue: No ]
  
• DSM-IV nicotine withdrawal symptom checklist [ Time Frame: Weeks 1, 4 and 8; 6-month follow-up ] [ Designated as safety issue: No ]
  

This pilot study utilizes a double-blind, two-armed design to evaluate the efficacy of combining oral selegiline with transdermal nicotine patch for smoking cessation in 40 nicotine-dependent smokers. After successful completion of 3 screening visits (to ensure medical and psychiatric eligibility criteria are met), subjects will be randomized into one of two experimental groups:

1. selegiline (10 mg/day) + NRT (21 mg/24 hr)
2. matching placebo + NRT (21 mg/24 hr)

Randomization will be performed through the use a random number list to generate 50% selegiline/50% placebo and also 50% male/50% female within each of those treatment groups.

Participants will begin selegiline (or placebo) once a day during Week 1, and dose will be graduated to full study dosage (10 mg/day) by adding an evening intake (a.m. and p.m. dosing) for Weeks 2-8. Day 15 of the trial represents target quit day and the transdermal nicotine patch (21 mg/24hr) will be applied at this time. Patches will be worn in conjunction with study medication for Weeks 3-8, after which the patch will be removed and study medication tapered throughout Week 9.

Subjects will present weekly to the Nicotine Dependence Clinic where they will provide breath, urine and blood samples as required, receive brief smoking cessation counseling and complete questionnaires regarding their smoking behavior and psychological state. A post-trial physical will be conducted upon completion of Week 9. Monthly follow-up phone interviews will be conducted for 5 months and subjects will be re-assessed in the NDC for a 6-month follow-up.

Trial Objectives

1. To determine if combination of selegiline hydrochloride and NRT (full substitution to tobacco) is superior to NRT alone + placebo (partial substitution) for smoking cessation in nicotine dependent smokers.

   • The primary hypothesis is that full substitution (selegiline + NRT) will be superior to placebo + NRT for achievement of 7-day point prevalence smoking abstinence rates at the end of trial abstinence rates (Day 49-56) assessment in nicotine-dependent cigarette smokers.
   • Secondary hypothesis 1a is that full substitution (selegiline + NRT) will be superior to NRT for achievement of last four weeks of trial (Days 29-56) smoking abstinence rates in nicotine-dependent cigarette smokers.
   • Secondary hypothesis 1b is that full substitution (selegiline + NRT) will be superior to NRT for achievement 6-month post target quit date smoking abstinence rates in nicotine-dependent cigarette smokers.
2. To determine if treatment retention and study medication compliance will be higher in the full substitution (selegiline + NRT) group as compared to the NRT group during the 8-week smoking cessation trial. Hypothesis 2 is that treatment retention and study medication compliance will be higher in the full substitution (selegiline + NRT) group as compared to the NRT group during the 8-week smoking cessation trial.
3. To determine if full substitution (selegiline + NRT) reduces nicotine craving and withdrawal symptoms as compared to NRT group during the 8-week smoking cessation trial. Hypothesis 3 is that full substitution treatment will lead to significant reductions in tobacco withdrawal and craving ratings compared to NRT group.
4. To determine adverse events profile in nicotine-dependent smokers of the combination of selegiline and NRT as compared to NRT.

Hypothesis 4 is that selegiline in combination with NRT will be well-tolerated and that rates of adverse events will not be significantly different between subjects assigned to full substitution as compared to NRT group.