Analgesia and hydration remain the only safe treatment for painful crises of sickle cell disease; hydroxyurea is effective, but the toxicity is still a problem. Piracetam is a nootropic drug that has reportedly been effective and non-toxic in sickle cell patients, but most studies were not placebo-controlled and included a small number of patients. The present study evaluated the drug in a double-blind crossed placebo-controlled clinical trial in 73 children and adolescents suffering from moderate to severe painful crises for 13 months. Information regarding frequency and severity of pain was acquired through monthly clinical evaluation, visits and house calls, and 4,300 weekly questionnaires filled out by the patients in their domiciles. A monthly pain score was calculated for each patient. Pain was the most frequent adverse manifestation of the disease stressing its significant bio-psycho-social impact. Although nearly all patients and relatives reported a better clinical course throughout the whole study, the drug was ineffective in the prevention of painful crises. This placebo effect may be ascribed to an unplanned and unsystematic ‘cognitive-behavioural’ management of the children. The pain score in the second semester of the study – both in the experimental and in the control groups – was significantly smaller than that in the first semester. In conclusion, piracetam was found to be ineffective in the prevention of painful crises; a powerful placebo effect due to adequate patient care was demonstrated.

1.
Serjeant GR: Screening for sickle-cell disease in Brazil. Lancet 2000;356:168–169.
2.
Paixão MC, Ferraz MHC, Januário JN, Viana MB, Lima JM: Reliability of isoelectrofocusing for the detection of Hb S, Hb C, and Hb D in a pioneering population-based program of newborn screening in Brazil. Hemoglobin 2001;25:297–303.
3.
Bunn HF: Pathogenesis and treatment of sickle cell disease. N Engl J Med 1997;337:762–769.
4.
Serjeant GR, Serjeant BE: The painful crisis; in Sickle Cell Disease, ed 3. Oxford, Oxford University Press, 2001, pp 281–300.
5.
Natarajan M, McIntire LV: Microvascular occlusion in sickle-cell anaemia. In: Pathophysiology and management of sickle cell pain crisis. Report of a Meeting of Physicians and Scientists, University of Texas Health Science Center at Houston, Texas. Lancet 1995;346:1408–1411.
6.
Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP: Mortality in sickle cell disease: Life expectancy and risk factors for early death. N Engl J Med 1994;330:1639–1644.
7.
Fuggle P, Shand PAX, Gill LJ, Daves SC: Pain, quality of life and coping in sickle cell disease. Arch Dis Child 1996;75:199–203.
8.
Williams I, Earles AN, Pack BB: Psychological considerations in sickle cell disease. Nurs Clin North Am 1983;18:215–229.
9.
Silva CM, Viana MB: Growth deficits in children with sickle cell disease. Arch Med Res 2002;33:308–312.
10.
Aluoch JR: The treatment of sickle cell disease: A historical and chronological literature review of the therapies applied since 1910. Trop Geogr Med 1984;36:1–26.
11.
National Institute of Health: Management and Therapy of Sickle Cell Disease, ed 3. Bethesda, National Institute of Health, 1995, NIH Publ No 96-2117, pp 1–114.
12.
de Montalembert M, Belloy M, Bernaudin F, Gouraud F, Capdeville R, Mardini R, Philippe N, Jais JP, Bardakdjian J, Ducrocq R, Maier-Redelsperger M, Elion J, Labie D, Girot R: Three-year follow-up of hydroxyurea treatment in severely ill children with sickle cell disease: The French Study Group on Sickle Cell Disease. J Pediatr Hematol Oncol 1997;19:313–318.
13.
Murayama M: Biochemical and physico-chemical alterations produced by piracetam on sickle cell blood. Proc Int Symp on Nootropic Drugs, Rio de Janeiro, Oct 1979, pp 205–210.
14.
Araújo JT, Nero GS: Piracetam in sickle-cell anemia. Lancet 1977;ii:411.
15.
Gini EK, Sonnet J: Use of piracetam improves sickle cell deformability in vitro and in vivo. J Clin Pathol 1987;40:99–102.
16.
Nalbandian RM, Henry RL, Burek CL, Diglio CA, Goldman AI, Taylor GW, Hoffman WH: Diminished adherence of sickle erythrocytes to cultured vascular endothelium by piracetam. Am J Hematol 1983;15:147–151.
17.
Asakura T, Ohnishi ST, Adachi K, Ozguc M, Hashimoto K, Devlin MT, Schwartz E: Effect of piracetam on sickle erythrocytes and sickle hemoglobin. Biochim Biophys Acta 1981;668:397–405.
18.
Franklin IM: Piracetam and sickle-cell disease. Lancet 1980;i:767–768.
19.
Stone PC, Chalder SM, Stuart J: Action of piracetam on cation flux and deformability of sickle cells. Clin Hemorheol 1988;8:779–790.
20.
Costa FF, Zago MA, Bottura C: Effects of piracetam and iodoacetamida on erythrocyte sickling. Lancet 1979;ii:1302.
21.
Riddington C, De Franceschi L: Drugs for preventing red blood cell dehydration in people with sickle cell disease. Cochrane Database Syst Rev. 2002;(4):CD003426.
22.
el-Hazmi MA, Warsy AS, al-Fawaz I, Opawoye AO, Taleb HA, Howsawi Z, Mohamed AA, Aly AW, Refai S, Sugathan PS, Rab AS, Ahmed HB, Abulaban M, Abdulkader AM, Farid M: Piracetam is useful in the treatment of children with sickle cell disease. Acta Haematol 1996;96:221–226.
23.
Sonnet J, Gini EK, Cornu G: Trial prevention of vaso-occlusive crises in homozygote sickle cell anemia using piracetam. Ann Soc Belge Méd Trop 1985;65:77–84.
24.
Nalbandian RM, Henry RL, Murayama M: Sickle-cell disease: Two new therapeutic strategies. Lancet 1978;ii:570–571.
25.
Mikatti MA, Solh HM, Deryan DE: A preliminary report on piracetam in sickle cell anemia: A double-blind cross-over clinical trial and effects on erythrocyte survival. King Faisal Spec Hosp Med J 1983;3:233–236.
26.
Frank LS, Greenberg CS, Stevens B: Pain assessment in infants and children. Pediatr Clin North Am 2000;47:487–512.
27.
Walco GA, Dampier CD: Pain in children and adolescents with sickle cell disease: A descriptive study. J Psychol 1990;15:643–658.
28.
McGrath PA: An assessment of children’s pain: A review of behavioral, physiological and direct scaling techniques. Pain 1987;31:147–176.
29.
Platt OS, Thorington BD, Brambilla DJ, Milner PF, Rosse WF, Vichinsky E, Kinney TR: Pain in sickle cell disease: Rates and risk factors. N Engl J Med 1991;325:11–16.
30.
Shapiro BS, Dinges DF, Orne EC, Bauer N, Reilly LB, Whitehouse WG, Ohene-Frempong K, Orne MT: Home management of sickle cell-related pain in children and adolescents: Natural history and impact on school attendance. Pain 1995;61:139–144.
31.
Westerman MP, Bailey K, Freels S, Schlegel R, Williamson P: Assessment of painful episode frequency in sickle-cell disease. Am J Hematol 1997;54:183–188.
32.
Nagel RL: Severity, pathobiology, epistatic effects and genetic markers in sickle cell anemia. Semin Hematol 1991;28:180–201.
33.
American Academy of Pediatrics: Committee on Genetics. Health supervision for children with sickle cell diseases and their families. Pediatrics 1996;98:467–472.
34.
Hillery CA: Potential therapeutic approaches for the treatment of vaso-occlusion in sickle cell disease. Curr Opin Hematol 1998;5:151–155.
35.
Steinberg MH: Management of sickle cell disease. N Engl J Med 1999;340:1021–1030.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.