Hostname: page-component-848d4c4894-wg55d Total loading time: 0 Render date: 2024-05-06T12:44:55.887Z Has data issue: false hasContentIssue false
  • English
  • Français

Use of a placebo in clinical trials

Published online by Cambridge University Press:  16 April 2020

G Emilien ,
JM Maloteaux ,
A Seghers  and
G Charles
G Emilien*
Affiliation:
Laboratory of Pharmacology & Department of Neurology
JM Maloteaux
Affiliation:
Laboratory of Pharmacology & Department of Neurology
A Seghers
Affiliation:
Department of Psychiatry, University Catholique de Louvain,Cliniques Universitaires Saint LucB-1200Brussels
G Charles
Affiliation:
37 Boulevard Paul Janson, 6000Charleroi, Belgium
*
*Correspondence and reprints: 127, rue Henri Prou, 78340 Les Clayes-Sous-Bois, France
Get access

Summary

The use of a placebo control group in the evaluation of a new product is today considered by most as a necessary condition of experimental drug research. Placebo response is an essential consideration in all clinical trials. If not properly controlled, incorrect and dangerous conclusion may be inferred for a product efficacy and safety profile. However, the inclusion of a placebo group in clinical trials in neuropsychiatric research raises several ethical and scientific questions. Whereas in certain indications, such as suicidal patients and severe and psychotic depression, the use of a placebo is generally not accepted, it is difficult to assess drug efficacy. This article discusses the concept of placebo in clinical trials, the occurrence of adverse events after placebo treatment and the high response rate of placebo in neuropsychiatric clinical research. The experimental methodology to adequately control all the factors involved is also analysed and discussed.

Keywords

placeboclinical trialmethodologyneuropsychiatric researchnocebo reaction
Type
Original article
Information
European Psychiatry , Volume 13 , Issue 5 , August 1998 , pp. 254 - 263
Copyright
Copyright © Elsevier, Paris 1998

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Albus, M, Lecrubier, Y, Maier, W, Butler, R, Rosenberg, R, Hip-pius, HDrug treatment of panic disorder: early response to treatment as a predictor of final outcome Acta Psychiatr Scand 82 1990 359–365CrossRefGoogle ScholarPubMed
Atkinson, ECDummy tablets BMJ 1 1958 1478CrossRefGoogle Scholar
Barsa, JAThe fallacy of the double-blind Am J Psychother 119 1963 1174–1175Google ScholarPubMed
Beecher, HKThe powerful placebo JAMA 159 1955 1602–1606CrossRefGoogle ScholarPubMed
Beneke, M, Rasmus, W, Fritze, JPlacebo response in antide-pressant drug trials Eur Psychiatry 9 1994 115–118CrossRefGoogle Scholar
Benson, H, Epstein, MDThe placebo effect: A neglected asset in the care of patients JAMA 232 1975 1225CrossRefGoogle ScholarPubMed
Blackwell, B, Bloomfield, SS, Buncher, CRDemonstration to medical students of placebo responses and non-drug factors Lancet 142 1972 1279–1282CrossRefGoogle Scholar
Bok, SLying Moral choice in public and private life 1978 PantheonGoogle Scholar
Bourne, HRRational use of placeboMelmon, KL eds Clinical pharmacology: basic principles in therapeutics, 2nd ed 1978 Macmillan New York1052–1062Google Scholar
Bowden, CL, Brugger, AM, Swann, AC, Calabresse, JR, Janicak, PG, Petty, Fet alEfficacy of divalproex vs lithium and placebo in the treatment of mania JAMA 271 1994 918–924CrossRefGoogle ScholarPubMed
Brodeur, DWA short history of placebos J Am Pharm Assoc 5 1965 642–662Google Scholar
Brown, WAPredictors of placebo response in depression Psy-chopharmacol Bull 24 1988 14–17Google ScholarPubMed
Buckalew, L, Ross, S, Starr, JNonspecific factors in drug effects: Placebo personality Psychol Rep 48 1981 3CrossRefGoogle ScholarPubMed
Collard, JMéthodologie en psychopharmacologie clinique 1973 Masson Paris31–38Google Scholar
Crombie, BWThe feet of clay of the double-blind trial Lancet 2 1963 994–997CrossRefGoogle Scholar
de Craen, AJM, Roos, PJ, de Vries, AL, Kleijnen, JEffect of colour of drugs: systematic review of perceived effect of drugs and of their effectiveness BMJ 313 1996 1625–1626CrossRefGoogle ScholarPubMed
Demarr, EWJ, Pellican, EWUse of placebos in therapy and in clinical pharmacology Mod Hasp 84 1955 108–118Google Scholar
Dobrilla, GPlacebo in the evaluation of antiulcer drugs Int J Tissue React 5 1983 329–337Google ScholarPubMed
Downing, RW, Rickeis, KSelf-report of hostility and the incidence of side reactions in neurotic out-patients treated with tranquilizing drugs and placebo J Consulting Psychol 31 1967 71–76CrossRefGoogle Scholar
Dubovsky, SLGeneralized anxiety disorder: new concepts and psychopharmacologic therapies J Clin Psychiatry 51 1990 3–10Google ScholarPubMed
Elander, GEthical conflicts in placebo treatment J Adv Nurs 16 1991 947–951CrossRefGoogle ScholarPubMed
Ernst, EThe power of placebo Let's use it to help as much as possible BMJ 313 1996 1569–1570CrossRefGoogle Scholar
Ernst, E, Resch, KLConcept of true and perceived placebo effects BMJ 311 1995 551–553CrossRefGoogle ScholarPubMed
Evans, FJThe power of a sugar pill Psychology Today April 1974 55–59Google Scholar
Fairchild, CJ, Rush, AJ, Vasavada, N, Giles, DE, Khatami, MWhich depressions respond to placebo Psychiatry Res 18 1986 217CrossRefGoogle ScholarPubMed
Fellner, CHTranquilizing drugs in general practice or the tri-umph of the impure placebo Am Pract Digest Treat 9 1958 1265–1268Google ScholarPubMed
Gram, L, Schmidt, DInnovative designs of controlled clinical trials in epilepsy Epilepsia 34suppl 71993 S1–S6CrossRefGoogle ScholarPubMed
Grunbaum, AThe placebo concept in medicine and psychiatry Psychol Med 16 1986 19–38CrossRefGoogle ScholarPubMed
Haas, H, Fink, H, Hartfelder, GDas placeboproblem Fortsehnte der Arzneimittelforschung 1 1959 279–454Google Scholar
Hailman, HFThe “blind placebo” in the evaluation of drugs J Am Med Assoc 151 1953 1430Google Scholar
Halikas, JAOrg 3770 (Mirtazapine) versus trazodone: A pla-cebo-controlled trial in depressed elderly patients Hum Psycho-pharmacol 10 1995 S125–S133CrossRefGoogle Scholar
Herzhaft, GThe nocebo effect Encephale 58 1969 486–503Google ScholarPubMed
Heylen, SLPlacebo response in schizophrenia: discussion Eur Psychiatry 9 1994 121–122CrossRefGoogle Scholar
Holm, S, Evans, MProduct names, proper claims? More ethical issues in the marketing of drugs BMJ 313 1996 1627–1629CrossRefGoogle ScholarPubMed
Honigfeld, GSpecific and non-specific factors in the treatment of depressed statesRickels, K ed Non specific factors in drug therapy 1968 Charles C Thomas Springfield80–107Google Scholar
Horvath, PPlacebos and common factors in two decades of psy-chotherapeutic research Psychol Bull 104 1988 214–225CrossRefGoogle Scholar
Hussain, MZEffect of shape of medication in treatment of anx-iety state Br J Psychiatr 120 1972 507–509CrossRefGoogle Scholar
Kennedy, WPThe nocebo reaction Med World 95 1961 203–205Google ScholarPubMed
Kleijnen, J, de Craen, AJM, Van Everdingen, J, Krol, LPlacebo effect in double-blind clinical trials: a review of interactions with medications Lancet 344 1994 1347–1349CrossRefGoogle ScholarPubMed
Lewander, TPlacebo response in schizophrenia Eur Psychiatry 9 1994 119–120CrossRefGoogle Scholar
Lipman, RS, Rickels, K, Uhlenhuth, EH, Park, LC, Fisher, SNeu-rotics who fail to take their drugs (letter) Br J Psychiatry 111 1965 1043CrossRefGoogle Scholar
Loebel, AD, Hyde, TS, Dunner, DLEarly placebo response in anxious patients J Clin Psychiatry 47 1986 230–232Google Scholar
Lyerly, SB, Ross, S, Krugman, AD, Clyde, DJDrugs place-bos. The effects of instructions upon performance and mood under amphetamine sulphate and chloral hydrate J Abnorm Soc Psychol 88 1964 321–327CrossRefGoogle Scholar
Mavissakalian, MR, Jones, B, Olson, SAbsence of placebo response in obsessive-compulsive disorder J Nerv Ment Dis 178 1990 268–270CrossRefGoogle ScholarPubMed
Merz, WAPlacebo response in panic disorder. A review Eur Psychiatry 9 1994 123–127CrossRefGoogle Scholar
Mowrer, OHLearning theory and behavior 1960 Wiley New YorkCrossRefGoogle Scholar
Oh, VMSMagic or medicine? Clinical pharmacological basis of placebo medication Am Acad Med Singapore 20 1991 31–37Google ScholarPubMed
Oh, VMSThe placebo effect: can we use it better BMJ 309 1994 69–70CrossRefGoogle ScholarPubMed
Pihl, RO, Altaian, JAn experimental analysis of the placebo effect J Clin Pharmacol 11 1971 91–95Google ScholarPubMed
Peck, C, Coleman, GImplications of placebo theory for clinical research and practice in pain management Theor Med 12 1991 247–270CrossRefGoogle ScholarPubMed
Quitkin, FM, Rabkin, JD, Markowitz, JM, Stewart, JW, McGrath, PJ, Harrison, WUse of pattern analysis to identify true drug response Arch Gen Psychiatry 44 1987 259–264CrossRefGoogle ScholarPubMed
Quitkin, FM, Stewart, JW, McGrath, PJ, Nunes, E, Ocepek-Welik-son, K, Tricamo, Eet alFurther evidence that a placebo response to antidepressants can be identified Am J Psychiatry 150 1993 566–570Google ScholarPubMed
Rabkin, JG, Stewart, JW, McGrath, PJ, Markowitz, JS, Harrison, W, Quitkin, FMBaseline characteristics of 10-day placebo washout responders in antidepressant trials Psychiatry Res 21 1987 9–22CrossRefGoogle ScholarPubMed
Research Committee of the Scottish Society of Physicians Br Med J 4 1971 755–784Google Scholar
Rickeis, KNon-specific factors in drug therapy of neurotic patientsNon specific factors in drug therapy 1968 Charles C Thomas Springfield3–26Google Scholar
Rickels, K, Lipman, R, Raab, EPrevious medication, duration of illness, and placebo responses J Nerv Dis 142 1966 548–554CrossRefGoogle Scholar
Rickels, K, Schweizer, E, Clary, C, Fox, I, Weise, CNefazodone and imipramine in major depression: A placebo-controlled trial Br J Psychiatry 164 1994 802–805CrossRefGoogle ScholarPubMed
Rosenberg, NK, Mellergard, M, Rosenberg, R, Beck, P, Otto-son, JOCharacteristics of panic disorder patients responding to placebo Acta Psychiatr Scand 365 1991 33–38CrossRefGoogle ScholarPubMed
Rosenzweig, P, Brohier, S, Zipfel, AThe placebo effect in healthy volunteers: Influence of experimental conditions on the adverse events profile during phase I studies Clin Pharmacol Ther 54 1993 578–583CrossRefGoogle ScholarPubMed
Rosenzweig, P, Brohier, S, Zippel, AThe placebo effect in healthy volunteers: influence of experimental conditions on physiological parameters during phase I studies Br J Clin Pharmacol 39 1995 657–664CrossRefGoogle ScholarPubMed
Schapira, K, McClelland, HA, Griffiths, NR, Newell, DJStudy of the effects of tablet colour in the treatment of anxiety states Brit Med J 2 1970 446–449CrossRefGoogle Scholar
Shapiro, AKA contribution to a history of the placebo effect Behav Sci 5 1960 398–430Google Scholar
Shapiro, AKA historic and heuristic definition of the placebo Psychiatry 27 1964 52–58CrossRefGoogle ScholarPubMed
Shapiro, AK, Struening, EL, Barten, H, Shapiro, ECorrelates of placebo reaction in an outpatient population Psychol Med 5 1975 389–396CrossRefGoogle Scholar
Shapiro, AK, Morris, LIThe placebo effect in medical and psychological theoryBergin, AGarfield, SHandbook of Psychotherapy and Behavioral Change.An Empirical Analysis 1978 John Wiley and Sons New YorkGoogle Scholar
Shapiro, AK, Shapiro, EPatient-provider relationships and the placebo effectMatarazzo, JDWeiss, SM eds Behavioral health: a handbook of health enhancement and disease prevention 1984 Wiley Interscience New York371–383Google Scholar
Scharf, MB, Roth, T, Vogel, GW, Walsh, JKA multicenter, pla-cebo-controlled study evaluating zolpidem in the treatment of chronic insomnia J Clin Psychiatry 55 1994 5Google ScholarPubMed
Stassen, HH, Angst, J, Delini-Stula, ASeverity at baseline onset of improvement in depression Meta-analysis of imipramine and moclobemide versus placebo Eur Psychiatry 9 1994 129–136CrossRefGoogle Scholar
Suchman, AL, Ader, RClassic conditioning and placebo effects in crossover studies Clin Pharmacol Ther 52 1992 372–377CrossRefGoogle ScholarPubMed
Thompson, C, Isaacs, GIs viloxazine an antidepressant? A pla-cebo-controlled double-blind study in major depressive disorder presenting in a general hospital Hum Psychopharmacol 6 1991 31–38CrossRefGoogle Scholar
Van Vliet, IM, Den Boer, JA, Westenberg, HGPsychopharmaco-logical treatment of social phobia: clinical and biochemical effects of brofaromine, a selective MAO-A inhibitor Eur Neuro-psychopharmacol 2 1992 21–29CrossRefGoogle Scholar
Versiani, M, Nardi, AE, Mundim, FD, Alves, AB, Liebowitz, MR, Amrein, RPharmacotherapy of social phobia: a controlled study with moclobemide and phenelzine Br J Psychiatry 161 1992 353–360CrossRefGoogle ScholarPubMed
Wilcox, CC, Cohn, JB, Linden, RD, Heiser, JF, Lucas, PB, Morgan, DL, DeFrancisco, DPredictors of placebo response: A retrospective analysis Psychopharmacol Bull 28 1992 157–162Google ScholarPubMed
Woodman, CL, Noyes, R, Ballenger, JC, Lydiard, RB, Sievers, G, Mihalko, DPredictors of response to alprazolam and placebo in patients with panic disorder J Affect Disorder 30 1990 5–13CrossRefGoogle Scholar
Zigmond, A, Snaith, RThe Hospital Anxiety Depression Scale Acta Psychiatr Scand 67 1983 361–370CrossRefGoogle Scholar
Zohar, J, Judge, ROCD Paroxetine study investigators Paroxetine versus clomipramine in the treatment of obsessive-compul-sive disorder Br J Psychiatry 169 1996 468–474CrossRefGoogle Scholar
Submit a response

Comments

No Comments have been published for this article.