Ethical questions in human clinical psychopharmacology: Should the focus be on placebo administration?

Journal of Psychopharmacology

Volumn 22, Issue 6, 2008, Pages 590-597

  Kotzalidis, G D ^a   Pacchiarotti, I ^a,b   Manfredi, G ^a   Savoja, V ^a,c   Torrent, C ^b   Mazzarini, L ^a   Tatarelli, C ^a   Amann, B ^b   Di Marzo, S ^a   Sanchez Moreno J ^b   Sani, G ^a   Girardi, P ^a   Colom, F ^b   Vieta, E ^b  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b HOSPITAL CLÍNIC   (Spain)

^c Centre Hospitralier Le Vinatier   (France)

Author keywords

Ethics; Placebo; Randomised clinical trials

Indexed keywords

ADINAZOLAM; ALPRAZOLAM; AMITRIPTYLINE; ANTIDEPRESSANT AGENT; BENZODIAZEPINE; CHLORPROMAZINE; DESIPRAMINE; DESVENLAFAXINE; DIAZEPAM; ESCITALOPRAM; IMIPRAMINE; NEUROLEPTIC AGENT; PALIPERIDONE; PLACEBO; RISPERIDONE;

CLINICAL PROTOCOL; CLINICAL RESEARCH; DEPRESSION; DRUG SCREENING; ETHICIST; HUMAN; MAJOR DEPRESSION; MANIA; PRIORITY JOURNAL; PROFESSIONAL STANDARD; PSYCHOPHARMACOLOGY; RESEARCH ETHICS; REVIEW;

CLINICAL TRIALS AS TOPIC; ETHICS, MEDICAL; HUMANS; MENTAL DISORDERS; PERIODICALS AS TOPIC; PLACEBOS; PSYCHOPHARMACOLOGY; PUBLISHING;

EID: 50249163827     PISSN: 02698811     EISSN: 14617285     Source Type: Journal    
DOI: 10.1177/0269881108089576     Document Type: Review

References (63)

1. Amsterdam, JD, Kaplan, M., Potter, L., Bloom, L., Rickels, K. (1986) Adinazolam, a new triazolobenzodiazepine, and imipramine in the treatment of major depressive disorder. Psychopharmacology (Berl) 88: 484-488.
2. Ansseau, M., Devoitille, JM, Papart, P., Vanbrabant, E., Mantanus, H., Timsit-Berthier, M. (1991) Comparison of adinazolam, amitriptyline, and diazepam in endogenous depressive inpatients exhibiting DST nonsuppression or abnormal contingent negative variation. J Clin Psychopharmacol 11: 160-165.
3. Basil, B., Adetunji, B., Mathews, M., Budur, K. (2006) Trial of risperidone in India-concerns. Br J Psychiatry 188: 489-490 ; author reply 490-491 ; discussion 491-492.
4. Berwick, D., Davidoff, F., Hiatt, H., Smith, R. (2001) Refining and implementing the Tavistock principles for everybody in health care. BMJ 323: 616-620.
5. Bowden, CL, Asnis, GM, Ginsberg, LD, Bentley, B., Leadbetter, R., White, R. (2004) Safety and tolerability of lamotrigine for bipolar disorder. Drug Saf 27: 173-184.
6. Bridge, JA, Iyengar, S., Salary, CB, Barbe, RP, Birmaher, B., Pincus, HA, et al. (2007) Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA 297: 1683-1696.
7. Calabrese, JR, Sullivan, JR, Bowden, CL, Suppes, T., Goldberg, JF, Sachs, GS, et al. (2002) Rash in multicenter trials of lamotrigine in mood disorders: clinical relevance and management. J Clin Psychiatry 63: 1012-1019.
8. Callahan, D. (2003) Individual good and common good: a communitarian approach to bioethics. Perspect Biol Med 46: 496-507.
9. Carlsson, A., Lindqvist, M. (1963) Effect of chlorpromazine and haloperidol on the formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol 20: 140-144.
10. Cattell, RB (1978). The Scientific Use of Factor Analysis in the Behavioral and Life Sciences. New York: Graywind.
11. Cohn, JB, Pyke, RE, Wilcox, CS (1988) Adinazolam mesylate and placebo in depressed outpatients: a 6-week, double-blind comparison. J Clin Psychiatry 49: 142-147.
12. Delay, J., Deniker, P., Harl, J-M. (1952) Traitement des états d'excitation et d'agitation par une méthode médicamenteuse derivée de l'hibernothérapie. Ann Méd-Psychol 110: 267-273.
13. Dunner, D., Myers, J., Khan, A., Avery, D., Ishiki, D., Pyke, R. (1987) Adinazolam-a new antidepressant: findings of a placebo-controlled, double-blind study in outpatients with major depression. J Clin Psychopharmacol 7: 170-172.
14. Emrich, HM, von Zerssen, D., Kissling, W., Möller, H-J., Windorfer, A. (1980) Effect of sodium valproate on mania. The GABAhypothesis of affective disorders. Arch Psychiatr Nervenkr 229: 1-16.
15. Evans, M. (2000) Justified deception? The single blind placebo in drug research. J Med Ethics 26: 188-193.
16. Evans, W., Hoyle, C. (1933) The comparative value of drugs used in the continuous treatment of angina pectoris. Q J Med 26 (new series, 2). 311-338.
17. Friend, WC, Weijer, C. (1996) CCNP position paper on the use of placebos in psychiatry [letter]. J Psychiatry Neurosci 21: 354-359.
18. Gold, H., Kwit, NT, Otto, H. (1937) The xanthines (theobromine and aminophylline) in the treatment of cardiac pain. JAMA 108: 2173-2179.
19. Greiner, T., Gold, H. (1952) Biologic considerations which determine the design. Biometrics 8: 232-237.
20. Hicks, F., Robins, E., Murphy, GE (1988) Comparison of adinazolam, amitriptyline, and placebo in the treatment of melancholic depression. Psychiatry Res 23: 221-227.
21. Hill, AB (1963) Medical ethics and controlled trials. BMJ 1: 1043-1049.
22. Hirsch, LJ, Weintraub, DB, Buchsbaum, R., Spencer, HT, Straka, T., Hager, M., et al. (2006) Predictors of lamotrigine-associated rash. Epilepsia 47: 318-322.
23. Kalueff, AV, Nutt, DJ (2006) Role of GABA in anxiety and depression. Depress Anxiety OnlineFirst 12-November-2006 (doi:10.1002/da.20262).
24. Kennedy, SH, de Groot, J., Ralevski, E., Reed, K. (1991) A comparison of adinazolam and desipramine in the treatment of major depression. Int Clin Psychopharmacol 6: 65-76.
25. Khan, A., Khan, S., Kolts, R., Brown, WA (2003) Suicide rates in clinical trials of SSRIs, other antidepressants, and placebo: analysis of FDA reports Am J Psychiatry 160: 790-792.
26. Khan, A., Khan, S., Leventhal, RM, Brown, WA (2001) Symptom reduction and suicide risk among patients treated with placebo in antipsychotic clinical trials: an analysis of the food and drug administration database. Am J Psychiatry 158: 1449-1454.
27. Khanna, S. (2006) Response to Dr Vikram Patel. Indian J Med Ethics 3: 17-18.
28. Khanna, S., Vieta, E., Lyons, B., Grossman, F., Eerdekens, M., Kramer, M. (2005) Risperidone in the treatment of acute mania: double-blind, placebo-controlled study. Br J Psychiatry 187: 229-234.
29. Korkeila, J., Salminen, JK, Hiekkanen, H., Salokangas, RK (2007) Use of antidepressants and suicide rate in Finland: an ecological study. J Clin Psychiatry 68: 505-511.
30. Lafaille, F., Welner, SA, Suranyi-Cadotte, BE (1991) Regulation of serotonin type 2 (5-HT2) and beta-adrenergic receptors in rat cerebral cortex following novel and classical antidepressant treatment. J Psychiatry Neurosci 16: 209-214.
31. Lasagna, L. (1995) The Helsinki Declaration: timeless guide or irrelevant anachronism ? J Clin Psychopharmacol 15: 96-98.
32. Martini, P. (1932) Methodenlehre der therapeutischen Untersuchung. Berlin: Verlag von Julius Springer.
33. Masand, P., Gupta, S., Dewan, M. (1991) Suicidal ideation related to fluoxetine treatment. N Engl J Med 324: 420.
34. Mayberg, HS, Silva, JA, Brannan, SK, Tekell, JL, Mahurin, RK, McGinnis, S., et al. (2002) The functional neuroanatomy of the placebo effect. Am J Psychiatry 159: 728-737.
35. Miller, FG, Wendler, D., Swartzman, LC (2005) Deception in research on the placebo effect. PLoS Med 2: e262.
36. Müller, WE, Schläfer, U., Wollert, U. (1978) Benzodiazepine receptor binding: the interactions of some non-benzodiazepine drugs with specific [3H] diazepam binding to rat brain synaptosomal membranes. Naunyn Schmiedebergs Arch Pharmacol 305: 23-26.
37. Murtagh, A., Murphy, KC (2006) Trial of risperidone in India-concerns. Br J Psychiatry 188: 489 ; author reply 490-491 ; discussion 491-492.
38. O'Connor, WT, Earley, B., Leonard, BE (1985) Antidepressant properties of the triazolobenzodiazepines alprazolam and adinazolam: studies on the olfactory bulbectomized rat model of depression. Br J Clin Pharmacol 19 (Suppl. 1). 49S - 56S.
39. Patel, V. (2006) Ethics of placebo-controlled trial in severe mania. Indian J Med Ethics 3: 11-12.
40. Paykel, ES, Hollyman, JA, Freeling, P., Sedgwick, P. (1988) Predictors of therapeutic benefit from amitriptyline in mild depression: a general practice placebo-controlled trial. J Affect Disord 14: 83-95.
41. Peralta, V., Cuesta, MJ (1995) Negative symptoms in schizophrenia: a confirmatory factor analysis of competing models. Am J Psychiatry 152: 1450-1457.
42. Peralta, V., Cuesta, MJ (1998) Factor structure and clinical validity of competing models of positive symptoms in schizophrenia. Biol Psychiatry 44: 107-114.
43. Peralta, V., Cuesta, MJ (1999) Dimensional structure of psychotic symptoms: an item-level analysis of SAPS and SANS symptoms in psychotic disorders. Schizophr Res 38: 13-26.
44. Peralta, V., Cuesta, MJ, de Leon, J. (1994) An empirical analysis of latent structures underlying schizophrenic symptoms: a four-syndrome model. Biol Psychiatry 36: 726-736.
45. Peralta, V., de Leon, J., Cuesta, MJ (1992) Are there more than two syndromes in schizophrenia? A critique of the positive-negative dichotomy. Br J Psychiatry 161: 335-343.
46. Quick, J. (2001) Maintaining the integrity of the clinical evidence base. Bull World Health Organ 79: 1093.
47. Rickels, K., Chung, HR, Csanalosi, IB, Hurowitz, AM, London, J., Wiseman, K., et al. (1987) Alprazolam, diazepam, imipramine, and placebo in outpatients with major depression. Arch Gen Psychiatry 44: 862-866.
48. Rickels, K., London, J., Fox, I., Hassman, H., Csanalosi, I., Weise, C. (1991) Adinazolam, diazepam, imipramine, and placebo in major depressive disorder: a controlled study. Pharmacopsychiatry 24: 127-131.
49. Rothman, KJ, Michels, KB (1994) The continuing unethical use of placebo controls. N Engl J Med 331: 394-398.
50. Sethy, VH, Hodges, DH (1982) Role of beta-adrenergic receptors in the antidepressant activity of alprazolam. Res Commun Chem Pathol Pharmacol 36: 329-332.
51. Shapiro, AK, Morris, LA (1978) The placebo effect in medical and psychological therapies. In: Garfield, SL, Bergin, AE, (eds). Handbook of Psychotherapy and Behavior Change: An Empirical Analysis, 2 nd edi., New York: John Wiley & Sons.
52. Smith, WT, Glaudin, V. (1986) Double-blind efficacy and safety study comparing adinazolam mesylate and placebo in depressed inpatients. Acta Psychiatr Scand 74: 238-245.
53. Srinivasan, S., Pai, SA, Bhan, A., Jesani, A., Thomas, G. (2006) Trial of risperidone in India-concerns. Br J Psychiatry 188: 489 ; author reply 490-1 ; discussion 491-492.
54. Storosum, JG, van Zwieten, BJ, van den Brink, W., Gersons, BP, Broekmans, AW (2001) Suicide risk in placebo-controlled studies of major depression. Am J Psychiatry 158: 1271-1275.
55. Storosum, JG, van Zwieten, BJ, Wohlfarth, T., de Haan, L., Khan, A., van den Brink, W. (2003) Suicide risk in placebo vs active treatment in placebo-controlled trials for schizophrenia. Arch Gen Psychiatry 60: 365-368.
56. Storosum, JG, Wohlfarth, T., Gispen-de Wied, CC, Linszen, DH, Gersons, BP, van Zwieten, BJ, et al. (2005) Suicide risk in placebo-controlled trials of treatment for acute manic episode and prevention of manic-depressive episode. Am J Psychiatry 162: 799-802.
57. Teicher, MH, Glod, C., Cole, JO (1990) Emergence of intense suicidal preoccupation during fluoxetine treatment. Am J Psychiatry 147: 207-210.
58. Tri-Council Working Group on Ethics (1997) Code of ethical conduct for research involving humans [final report]. The Medical Research Council of Canada, the Natural Sciences and Engineering Research Council of Canada, and the Social Sciences and Humanities Research Council of Canada, Ottawa.
59. Venkatakrishnan, K., Culm, KE, Ehrenberg, BL, Harmatz, JS, Corbett, KE, Fleishaker, JC, et al. (2005) Kinetics and dynamics of intravenous adinazolam, N-desmethyl adinazolam, and alprazolam in healthy volunteers. J Clin Pharmacol 45: 529-537.
60. Vieta, E. (2002) Do we need placebo control in maintenance studies in bipolar disorders? Bipolar Disord 4 (Suppl 1). 61.
61. Vieta, E. (2007) Psychiatry: from interest in conflicts to conflicts of interest. World Psychiatry 6: 27-29.
62. Vieta, E., Carné, X. (2005) The use of placebo in clinical trials on bipolar disorder: a new approach for an old debate. Psychother Psychosom 74: 10-16.
63. Young, SN, Annable, L. (1996) The use of placebos in psychiatry: a response to the draft document prepared by the Tri-Council Working Group. Canadian College of Neuropsychopharmacology. J Psychiatry Neurosci 21: 235-238.