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Perceived Medication Assignment during a Placebo-Controlled Laboratory Study of Varenicline: Temporal Associations of Treatment Expectancies with Smoking-Related Outcomes

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Abstract

Rationale

Expectancies regarding treatment assignment may influence outcomes in placebo-controlled trials above and beyond actual treatment assignment. For smoking pharmacotherapies, guessing enrollment in the active medication treatment is associated with higher abstinence rates. However, placebo-controlled trials of smoking pharmacotherapies rarely assess perceived treatment assignment and those that do only collect this information after reaching full dosage.

Objectives

To determine the temporal relationship between treatment expectancies and smoking-related variables, we assessed the impact of treatment guess during a placebo-controlled laboratory study of varenicline on measures of craving, smoking reward, and smoking reinforcement. We hypothesized that treatment guess at mid-titration would influence smoking-related measures at full dosage, above and beyond actual medication effects. We also explored factors related to guess stability and differences in blind fidelity between mid-drug titration and full dosage.

Methods

Eighty-eight participants completed laboratory assessments at baseline, mid-titration, and full dosage that involved self-report and behavioral measures of tonic craving, cue-provoked craving, smoking reward, and smoking reinforcement. Participants guessed treatment assignment at mid-titration and full dosage.

Results

Generalized linear models confirmed that, beyond actual treatment assignment, treatment guess improved model fit for both self-report and behavioral smoking-related measures. Further, accuracy of treatment guess improved from titration to full dosage, and specific demographic factors (e.g., gender, race) were associated with type of treatment guess and guess stability across time.

Conclusions

These results reinforce the importance of assessing perceived treatment assignment repeatedly during placebo-controlled trials and suggest that treatment expectancies during titration can affect outcomes once full dosage has been reached.

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References

  • Bailey SR, Fong DM, Bryson W, Fortmann SP, Killen JD (2010) Perceived drug assignment and treatment outcome in smokers given nicotine patch therapy. J Subst Abuse Treat 39:150–156

    Article  PubMed Central  PubMed  Google Scholar 

  • Benedetti F (2008) Mechanisms of placebo and placebo-related effects across diseases and treatments. Annu Rev Pharmacol Toxicol 48:33–60

    Article  CAS  PubMed  Google Scholar 

  • Biener L, Abrams DB (1991) The Contemplation Ladder: validation of a measure of readiness to consider smoking cessation. Health Psychol 10:360–365

    Article  CAS  PubMed  Google Scholar 

  • Brandon TH, Drobes DJ, Unrod M, Heckman BW, Oliver JA, Roetzheim RC, Karver SB, Small BJ (2011) Varenicline effects on craving, cue reactivity, and smoking reward. Psychopharmacol 218:391–403

    Article  CAS  Google Scholar 

  • Buchanan TS, Sanderson Cox L, Thomas JL, Nollen NL, Berg CJ, Mayo MS, Ahluwalia JS (2013) Perceived treatment assignment and smoking cessation in a clinical trial of bupropion versus placebo. Nicotine Tob Res 15:567–571

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cappelleri JC, Bushmakin AG, Baker CL, Merikle E, Olufade AO, Gilbert DG (2007) Confirmatory factor analyses and reliability of the modified cigarette evaluation questionnaire. Addict Behav 32:912–923

    Article  PubMed  Google Scholar 

  • Carter BL, Robinson JD, Lam CY, Wetter DW, Tsan JY, Day SX, Cinciripini PM (2006) A psychometric evaluation of cigarette stimuli used in a cue reactivity study. Nicotine Tob Res 8:361–369

    Article  PubMed  Google Scholar 

  • Center for the Study of Emotion and Attention (1995) The International Affective Picture System [photographic slides]. The Center for Research in Psychophysiology. University of Florida, Gainesville

    Google Scholar 

  • Dar R, Stronguin F, Etter JF (2005) Assigned versus perceived placebo effects in nicotine replacement therapy for smoking reduction in Swiss smokers. J Consult Clin Psychol 73:350–353

    Article  PubMed  Google Scholar 

  • Drobes DJ (2002) Cue reactivity in alcohol and tobacco dependence. Alcohol Clin Exp Res 26:1928–1929

    Article  PubMed  Google Scholar 

  • Etter JF, Schneider NG (2013) An internet survey of use, opinions and preferences for smoking cessation medications: nicotine, varenicline, and bupropion. Nicotine Tob Res 15:59–68

    Article  CAS  PubMed  Google Scholar 

  • Fairbairn CE, Dundon WD, Xie H, Plebani JG, Kampman KM, Lynch KG (2008) Study blinding and correlations between perceived group assignment and outcome in a cocaine pharmacotherapy trial. Am J Addict 17:387–391

    Article  PubMed Central  PubMed  Google Scholar 

  • Finniss DG, Kaptchuk TJ, Miller F, Benedetti F (2010) Biological, clinical, and ethical advances of placebo effects. Lancet 375:686–695

    Article  PubMed Central  PubMed  Google Scholar 

  • First MB, Spitzer RL, Gibbon M, Williams JBW (1996) Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). American Psychiatric Press, Inc., Washington

    Google Scholar 

  • Fucito LM, Toll BA, Salovey P, O'Malley SS (2009) Beliefs and attitudes about bupropion: implications for medication adherence and smoking cessation treatment. Psychol Addict Behav 23:373–379

    Article  PubMed Central  PubMed  Google Scholar 

  • Gonzales D, Rennard SI, Nides M, Oncken C, Azoulay S, Billing CB, Watsky EJ, Gong J, Williams KE, Reeves KR (2006) Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA 296:47–55

    Article  CAS  PubMed  Google Scholar 

  • Gottlieb AM, Killen JD, Marlatt GA, Taylor CB (1987) Psychological and pharmacological influences in cigarette smoking withdrawal: effects of nicotine gum and expectancy on smoking withdrawal symptoms and relapse. J Consult Clin Psychol 55:606–608

    Article  CAS  PubMed  Google Scholar 

  • Griffiths RR, Troisi JR, Silverman K, Mumford GK (1993) Multiple-choice procedure: an efficient approach for investigating drug reinforcement in humans. Behav Pharmacol 4:3–13

    Article  CAS  PubMed  Google Scholar 

  • Hall SM, Gorecki JA, Reus VI, Humfleet GL, Muñoz RF (2007) Belief about drug assignment and abstinence in treatment of cigarette smoking using Nortriptyline. Nicotine Tob Res 9:467–471

    Article  CAS  PubMed  Google Scholar 

  • Harrell PT, Juliano LM (2012) A direct test of the influence of nicotine response expectancies on the subjective and cognitive effects of smoking. Exp Clin Psychopharmacol 20:278–286

    Article  PubMed  Google Scholar 

  • Heatherton TF, Kozlowski LT, Frecker RC, Fagerström KO (1991) The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire. Br J Addict 86:1119–1127

    Article  CAS  PubMed  Google Scholar 

  • Hughes JR, Pickens RW, Spring W, Keenan RM (1985) Instructions control whether nicotine will serve as a reinforcer. J Pharmacol Exp Ther 235:106–112

    CAS  PubMed  Google Scholar 

  • Jorenby DE, Hays JT, Rigotti NA, Azoulay S, Watsky EJ, Williams KE, Billing CB, Gong J, Reeves KR (2006) Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA 296:56–63

    Article  CAS  PubMed  Google Scholar 

  • Juliano LM, Brandon TH (2002) Effects of nicotine dose, instructional set, and outcome expectancies on the subjective effects of smoking in the presence of a stressor. J Abnorm Psychol 111:88–97

    Article  PubMed  Google Scholar 

  • Kelemen WL, Kaighobadi F (2007) Expectancy and pharmacology influence the subjective effects of nicotine in a balanced-placebo design. Exp Clin Psychopharmacol 15:93–101

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kidorf M, Stitzer ML, Griffiths RR (1995) Evaluating the reinforcement value of clinic-based privileges through a multiple choice procedure. Drug Alcohol Depend 39:167–172

    Article  CAS  PubMed  Google Scholar 

  • Kirsch I (1997) Specifying nonspecifics: psychological mechanisms of placebo effects. In: Harrington A (ed) The placebo effect: an interdisciplinary exploration. Harvard University Press, Cambridge, pp 166–186

    Google Scholar 

  • Margraf J, Ehlers A, Roth WT, Clark DB, Sheikh J, Agras WS, Taylor CB (1991) How "blind" are double-blind studies? J Consult Clin Psychol 59:184–187

    Article  CAS  PubMed  Google Scholar 

  • McKee S, Harrison E, Shi J (2010) Alcohol expectancy increases positive responses to cigarettes in young, escalating smokers. Psychopharmacol 210:355–364

    Article  CAS  Google Scholar 

  • Mooney M, White T, Hatsukami D (2004) The blind spot in the nicotine replacement therapy literature: assessment of the double-blind in clinical trials. Addict Behav 29:673–684

    Article  PubMed  Google Scholar 

  • Nelder JA, Wedderburn RWM (1972) Generalized linear models. J R Stat Soc Ser A 135:370–384

    Article  Google Scholar 

  • Perkins KA, Sayette M, Conklin C, Caggiula A (2003) Placebo effects of tobacco smoking and other nicotine intake. Nicotine Tob Res 5:695–709

    Article  CAS  PubMed  Google Scholar 

  • Perkins KA, Doyle T, Ciccocioppo M, Conklin C, Sayette M, Caggiula A (2006) Sex differences in the influence of nicotine dose instructions on the reinforcing and self-reported rewarding effects of smoking. Psychopharmacol 184:600–607

    Article  CAS  Google Scholar 

  • Reid MS, Palamar J, Raghavan S, Flammino F (2007) Effects of topiramate on cue-induced cigarette craving and the response to a smoked cigarette in briefly abstinent smokers. Psychopharmacol 192:147–158

    Article  CAS  Google Scholar 

  • Schnoll RA, Epstein L, Audrain J, Niaura R, Hawk L, Shields PG, Lerman C, Wileyto EP (2008) Can the blind see? Participant guess about treatment arm assignment may influence outcome in a clinical trial of bupropion for smoking cessation. J Subst Abuse Treat 34:234–241

    Article  PubMed Central  PubMed  Google Scholar 

  • Shiffman S, Ferguson SG, Rohay J, Gitchell JG (2008) Perceived safety and efficacy of nicotine replacement therapies among US smokers and ex-smokers: relationship with use and compliance. Addiction 103:1371–1378

    Article  PubMed  Google Scholar 

  • Thomas JL, Guo H, Lynam IM, Powell JN, Okuyemi KS, Bronars CA, Ahluwalia JS (2008) The impact of perceived treatment assignment on smoking cessation outcomes among African-American smokers. J Gen Intern Med 23:1361–1366

    Article  PubMed Central  PubMed  Google Scholar 

  • Tiffany ST, Drobes DJ (1991) The development and initial validation of a questionnaire on smoking urges. Br J Addict 86:1467–1476

    Article  CAS  PubMed  Google Scholar 

  • Wray JM, Gass JC, Tiffany ST (2013) A systematic review of the relationships between craving and smoking cessation. Nicotine Tob Res 15:1167–1182

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded by Pfizer, Inc. via Investigator Initiated Research Grant #GA3051LP. Pfizer, Inc. also supplied the investigators with medication and placebo used in the study.

Conflict of interest

Dr. Brandon has served as a member of the Varenicline Advisory Board for Pfizer and consulted on the development of the online behavioral adjuvant that is made available to varenicline users. Dr. Drobes served as a reviewer for the Pfizer 2011 Global Research Awards for Nicotine Dependence (GRAND) program. All other authors report no conflicts of interest.

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Authors and Affiliations

  1. Department of Psychology, University of South Florida, Tampa, FL, USA

    John B. Correa, Bryan W. Heckman, Nicole S. Marquinez, David J. Drobes, Marina Unrod & Thomas H. Brandon

  2. Department of Health Outcomes & Behavior, H. Lee Moffitt Cancer Center, Tampa, FL, USA

    David J. Drobes, Marina Unrod, Richard G. Roetzheim & Thomas H. Brandon

  3. Department of Family Medicine, University of South Florida, Tampa, FL, USA

    Richard G. Roetzheim

  4. Tobacco Research & Intervention Program, H. Lee Moffitt Cancer Center & Research Institute, 4115 E. Fowler Avenue, Tampa, FL, 33617, USA

    Thomas H. Brandon

Authors
  1. John B. Correa
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  2. Bryan W. Heckman
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  3. Nicole S. Marquinez
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  4. David J. Drobes
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  5. Marina Unrod
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  6. Richard G. Roetzheim
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  7. Thomas H. Brandon
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Correspondence to Thomas H. Brandon.

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Correa, J.B., Heckman, B.W., Marquinez, N.S. et al. Perceived Medication Assignment during a Placebo-Controlled Laboratory Study of Varenicline: Temporal Associations of Treatment Expectancies with Smoking-Related Outcomes. Psychopharmacology 231, 2559–2566 (2014). https://doi.org/10.1007/s00213-013-3420-2

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  • DOI: https://doi.org/10.1007/s00213-013-3420-2

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