Addicted to Nicotine
A National Research Forum

Section VI: Treatment of Nicotine Dependence
John Hughes, M.D., Chair

COMBINED TREATMENTS

Maxine L. Stitzer, Ph.D.
Bayview Medical Center
Johns Hopkins University School of Medicine

Introduction

At present, the best methods for treating tobacco dependence involve combined use of behavioral and pharmacologic therapies. Because they operate by different mechanisms, complimentary and potentially additive effects may be expected when behavioral and pharmacologic treatments are used in combination. This presentation will focus on nicotine replacement therapy (NRT) combined with counseling that includes support and relapse prevention problemsolving, since these have been the most widely researched treatment methods.

What We Know

Absolute rates of successful quitting are enhanced by combined therapy compared with single therapies, with effects being additive or less than additive. There is evidence both that behavior therapy enhances the efficacy of NRT and that NRT enhances the efficacy of behavior therapy. Typical long-term (6 to 12 months) abstinence rates for single therapies are on the order of 20 to 25 percent, while combined therapies can produce long-term abstinence rates as high as 35 to 40 percent. Thus, combined therapies produce quit rates greater than those generally produced by either treatment intervention alone and substantially better than general population quit rates of 5 percent or less.

Three mechanisms have been suggested to account for improved efficacy with combined therapies: (1) enhanced compliance with treatment interventions, (2) independent effects on different outcome targets (withdrawal relief producing better initial abstinence versus new coping skills producing better long-term outcomes), and (3) independent effects on different populations such that some people benefit from pharmacotherapy and others from behavior therapy. Data are available only for the second mechanism listed.

Combined therapies appear to raise the absolute percentage of smokers who remain abstinent; this effect is apparent from the earliest postquit measurement timepoint. This is an important observation, as early smoking behavior is a very powerful predictor of subsequent success versus failure. Approximately 90 percent of smokers who have lapses during the first 2 postquit weeks of combined therapy go on to fail in that quit attempt, while only 50 percent of early abstainers ultimately return to smoking. The role of withdrawal suppression here is controversial. With the exception of craving, symptom suppression has not been reliably related to abstinence success.

Evidence for relapse prevention effects of therapies that extend beyond the initial few postquit weeks is sparse. In order to examine these relapse prevention effects, it is useful to start with a group of uniformly abstinent subjects who are then randomly assigned to experimental and control therapies. One such study showed that smokers who received behavior therapy had slower rates of relapse compared with those who received no treatment. The specific role of relapse prevention skills training in slowing relapse is unclear.

The following facts hold true for combined treatment for tobacco dependence:

• Combined treatments produce additive effects on abstinence rates compared with single treatments.

• Combined treatments can produce long-term (6 to 12 months) abstinence rates as high as 35 to 40 percent.

• People who can go without smoking in postquit weeks 1 to 2 are more likely to succeed; combined treatments increase the number of early postquit abstainers.

What We Need To Know More About

Four issues stand out as important for future research and development:

• Compliance. Compliance is important to ensure exposure to adequate amounts and durations of therapy components. We need to know whether behavior therapy enhances compliance with medications use (e.g., through instruction, monitoring, and support) and whether pharmacologic therapy enhances compliance with behavior therapy (e.g., by allowing the person to focus on behavior change rather than the discomfort of withdrawal). Including compliance measures in treatment outcome research would help to address this issue.

• Early Abstinence. If combined therapies work by increasing initial abstinence success, how do they produce this effect? For example, is there an interaction between withdrawal suppression and social support provided by counseling that enhances abstinence rates? What is the role of relapse prevention coping skills, if any (e.g., does therapy prompt and support performance of existing skills versus teaching new skills)? Does either therapy act to attenuate the effects of early reexposure to smoking (slips and lapses)? For example, pharmacotherapy could attenuate priming effects of nicotine exposure while behavior therapy counteracted the abstinence violation effect. An increased focus on dynamics of early postquit weeks would be useful.

• Relapse Prevention. We need to know whether any existing therapies can slow relapse, particularly after therapy ends; if so, how this is accomplished? For example, do people actually learn new skills or alter their behavior as a result of receiving behavior therapy, and does this prevent relapse? Would longer durations of medication or behavior therapy be helpful to slow relapse rates? Is there a safe time after which relapse is no longer likely? Increased focus on relapse prevention is important for improving the long-term success of combined therapies.

• Treatment Delivery . Efficacious treatments are currently available, but these cannot have an impact unless they are used. We need to know how to improve access, affordability, and acceptability of both pharmacologic and behavioral therapies in order to take advantage of existing treatments (over-the-counter nicotine replacement is a good start) and how to strengthen the linkage between the two therapy types. This is a challenge, given that the majority of smokers prefer to quit on their own without seeking help.

The following represent areas that require additional research:

• More about compliance interactions. Does either type of therapy enhance compliance with the other?

• More about early abstinence. How do pharmacologic and behavioral treatments interact to increase early abstinence rates?

• Can anything be done to counteract effects of slips and lapses?

• More about relapse prevention. Do any existing treatments slow relapse? Can relapse be slowed by intensifying or prolonging existing treatments?

• More about treatment utilization. How can access, affordability, and acceptability be improved for existing efficacious treatments?

Recommended Reading

Anthonisen, N.R.; Connett, J.E.; Kiley, J.P.; Altose, M.D.; Bailey, W.C.; Buist, A.S.; Conway, W.A., Jr.; Enright, P.L.; Kanner, R.E.; O'Hara, P.; et al. Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. JAMA 272:1497-1505, 1994.

Brandon, T.H.; Zelman, D.C.; and Baker, T.B. Effects of maintenance sessions on smoking relapse: Delaying the inevitable? J Consult Clin Psychol 55:780-782, 1987.

Fiore, M.C.; Bailey, W.C.; Cohen, S.J.; Dorfman, S.F.; Goldstein, M.G.; Gritz, E.R.; Heyman, R.B.; and Holbrook, J. Smoking Cessation: Clinical Practice Guideline No. 18. AHCPR Pub. No. 96-0692. Rockville, MD: U.S. Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1996.

Fiore, M.C.; Kenford, S.L.; Jorenby, D.E.; Wetter, D.W.; Smith, S.S.; and Baker, T.B. Two studies of the clinical effectiveness of the nicotine patch with different counseling treatments. Chest 105:524-533, 1994.

Hughes, J.R. Combined psychological and nicotine gum treatment for smoking: A critical review. J Subst Abuse 3:337-350, 1991.

Kenford, S.L.; Fiore, M.C.; Jorenby, D.E.; Smith, S.S.; Wetter, D.; and Baker, T.B. Predicting smoking cessation. Who will quit with and without the nicotine patch? JAMA 271:589-594, 1994.

Patten, C.A., and Martin, J.E. Does nicotine withdrawal affect smoking cessation? Clinical and theoretical issues. Ann Behav Med 18:190-200, 1996.

Transdermal Nicotine Study Group. Transdermal nicotine for smoking cessation. Six-month results from two multicenter controlled clinical trials. JAMA 266:3133-3138, 1991.