Child Psychiatry and Human Development

, Volume 39, Issue 3, pp 237–245 | Cite as

A Double-blind Placebo Controlled Trial of Piracetam Added to Risperidone in Patients with Autistic Disorder

  • Shahin AkhondzadehEmail author
  • Hamid Tajdar
  • Mohammad-Reza Mohammadi
  • Mohammad Mohammadi
  • Gholam-Hossein Nouroozinejad
  • Omid L. Shabstari
  • Hossein-Ali Ghelichnia
Original Paper


It has been reported that autism is a hypoglutamatergic disorder. Therefore, it was of interest to assess the efficacy of piracetam, a positive modulator of AMPA-sensitive glutamate receptors in autistic disorder. About 40 children between the ages three and 11 years (inclusive) with a DSM IV clinical diagnosis of autism and who were outpatients from a specialty clinic for children were recruited. The children presented with a chief complaint of severely disruptive symptoms related to autistic disorder. Patients were randomly allocated to piracetam + risperidone (Group A) or placebo + risperidone (Group B) for a 10-week, double-blind, placebo-controlled study. The dose of risperidone was titrated up to 2 mg/day for children between 10 and 40 kg and 3 mg/day for children weighting above 40 kg. The dose of piracetam was titrated up to 800 mg/day. Patients were assessed at baseline and after 2, 4, 6, 8 and 10 weeks of starting medication. The measure of the outcome was the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale (total score). The ABC-C Rating Scale scores improved with piracetam. The difference between the two protocols was significant as indicated by the effect of group, the between subjects factor (F = 5.85, d.f. = 1, P = 0.02). The changes at the endpoint compared with baseline were: −11.90 ± 3.79 (mean ± SD) and −5.15 ± 3.04 for group A and B respectively. A significant difference was observed on the change in scores in the ABC-C Rating Scale in week 10 compared with baseline in the two groups (t = 6.017, d.f. = 38, P < 0.0001). The results suggest that a combination of atypical antipsychotic medications and a glutamate agent such as piracetam, might have increase synergistic effects in the treatment of autism.


AMPA Autism Glutamate Piracetam 


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This study was Dr. Hamid Tajdar’s postgraduate thesis and was supported by a grant from Tehran University of Medical Sciences. The authors would like to thank to the staff of Pharmacy of Roozbeh Psychiatric Hospital.


  1. 1.
    Rutter M, Silberg J, O’Connor T, Simonoff E (1999) Genetics and child psychiatry, II: empirical research findings. J Child Psychol Psychiatry 40:19–55CrossRefPubMedGoogle Scholar
  2. 2.
    Chakrabarti S, Fombonne E (2001) Pervasive developmental disorders in preschool children. JAMA 285:3039–3099CrossRefGoogle Scholar
  3. 3.
    Lord C, Leventhal BL, Cook EH Jr (2001) Quantifying the phenotype in autism spectrum disorders. Am J Med Genet 105:36–38CrossRefPubMedGoogle Scholar
  4. 4.
    Polleux F, Lauder JM (2005) Toward a developmental neurobiology of autism. Men Retard Dev Disabil 10:303–317CrossRefGoogle Scholar
  5. 5.
    Anderson LT, Campbell M, Adams P, Small AM, Perry R, Shell J (1989) The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children. J Autism Dev Disord 19:227–239CrossRefPubMedGoogle Scholar
  6. 6.
    Campbell M, Adams P, Perry R, Spencer EK, Overall JE (1988) Tardive and withdrawal dyskinesia in autistic children: a prospective study. Psychopharmacol Bull 24:251–255PubMedGoogle Scholar
  7. 7.
    Levy SE, Hyman SL (2005) Novel treatments for autistic spectrum disorders. Men Retard Develop disab 11:131–142CrossRefGoogle Scholar
  8. 8.
    Nilsson M, Waters S, Waters N (2001) A behavioral pattern analysis of hypoglutamatergic mice: effects of four different antipsychotic agents. J Neural Transm 108:1181–1196CrossRefPubMedGoogle Scholar
  9. 9.
    Purecell AE, Jeon OH, Zimmerman AW (2001) Postmortem brain abnormalities of the glutamate neurotransmitter system in autism. Neurology 57:1618–1628Google Scholar
  10. 10.
    Serajee FJ, Zhong H, Nabi R, Huq AH (2003) The metabotropic glutamate receptor 8 gene at 7q31: partial duplication and possible association with autism. J Med Genet 40:e42CrossRefPubMedGoogle Scholar
  11. 11.
    Akhondzadeh S, Erfani S, Mohammadi MR, Tehranidoost M, Amini H (2004) Cyproheptadine in the treatment of autistic disorder: a double-blind and placebo controlled trial. J Clin Pharm Therapeutics 29:145–150CrossRefGoogle Scholar
  12. 12.
    Pickett J, London E (2005) The neuropathology of autism: areview. J Neuropathol Exp Neurol 64: 925–935CrossRefPubMedGoogle Scholar
  13. 13.
    Carlsson ML (1998) Hypothesis: is infantile autism a hypoglutamatergic disorder? Relevance of glutamate-serotonin interaction for pharmacotherapy. J Neural Transm 105:525–535CrossRefPubMedGoogle Scholar
  14. 14.
    Maurel Remy S, Bervoets K, Millan MJ (1995) Blockade of phencyclidine-induced hyperlocomotion by clozapine and MDL 100,907 in rats reflects antagonism of 5HT2A receptors. Eur J Pharmacol 280: 367–379CrossRefGoogle Scholar
  15. 15.
    Krystal JH, D’Souza DC, Petrakis IL, Beiger A, Berman R, Charney DS, Abi-Saab W, Madonick S (1999) NMDA agonists and antagonists as probes of glutamatergic dysfunction and pharmacotherapies for neuropsychiatric disorders. Harv Rev Psychiatry 7:125–133CrossRefPubMedGoogle Scholar
  16. 16.
    Goff DC, Tsai G, Levitt J, Amico E, Manoach D, Schoenfield DA, Hayden DL, McCarley R. Coyle JT (1999) A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia. Arch Gen Psychiatry 56:21–27CrossRefPubMedGoogle Scholar
  17. 17.
    Noorbala AA, Akhondzadeh S, Davari-Astiani R, Amini-Nooshabadi H (1999) Piracetam in the treatment of schizophrenia: implications for the glutamate hypothesis of schizophrenia. J Clin Pharm Therapeutics 24:369–374CrossRefGoogle Scholar
  18. 18.
    Cohen SA, Muller WE. (1993) Effects of piracetam on N- methyl-d-aspartate receptor properties in the aged mouse brain. Pharmacol 47:217–222CrossRefGoogle Scholar
  19. 19.
    Gouliaev AH, Senning A (1994) Piracetam and other structurally related nootropics. Brain Res Rev 19:180–222CrossRefPubMedGoogle Scholar
  20. 20.
    Copani A, Genazzani AA, Aleppo G (1999) Nootropic drugs positively modulate alpha-amino- 3- hydroxy-5-methyl-4-isoxazolpropionic acid-sensitive glutamate receptors in neuronal cultures. J␣Neurochem 54:1199–1204Google Scholar
  21. 21.
    American Psychiatric Association (APA) (1994) Diagnosis and statistical manual of mental disorders. American Psychiatric Association, Washington, DCGoogle Scholar
  22. 22.
    World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects (2000) available from: Access date 03 Jun 2007
  23. 23.
    Aman MG, Singh NN, Stewart AW, Field CJ (1985) The aberrant behavior checklist: a behavior rating scale for assessment of treatment effects. Am J Men Deficit 89:485–491Google Scholar
  24. 24.
    Chouinard G, Ross-Chouinard A, Annables L, Jones BD (1980) Extrapyramidal symptoms rating scale (abstract). Can J Neurol Sci 7:233Google Scholar
  25. 25.
    Akhondzadeh S (1998) The glutamate hypothesis of schizophrenia. J Clin Pharm Therapeutics 23: 243–246CrossRefGoogle Scholar
  26. 26.
    Posey DJ, Kem DL, Swiezy NB, Sweeten TL, Wiegand RE, McDougle CJ (2004) A pilot study of D-cycloserine in subjects with autistic disorder. Am J Psychiatry 161:2115–2117CrossRefPubMedGoogle Scholar
  27. 27.
    Levi G, Sechi E (1987) A study of piracetam in the pharmacological treatment of learning disabilities. In: Bakker D (ed) Child health and development, developmental dyslexia and learning disorders, vol. 5. Karger, Basel, pp 129–139Google Scholar
  28. 28.
    Winblad B (2005) Piracetam: a review of pharmacological properties and clinical uses. CNS Drug Rev 11:169–182PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Shahin Akhondzadeh
    • 1
    Email author
  • Hamid Tajdar
    • 1
  • Mohammad-Reza Mohammadi
    • 1
  • Mohammad Mohammadi
    • 2
  • Gholam-Hossein Nouroozinejad
    • 3
  • Omid L. Shabstari
    • 4
  • Hossein-Ali Ghelichnia
    • 5
  1. 1.Psychiatric Research Center, Roozbeh Psychiatric HospitalTehran University of Medical SciencesTehranIran
  2. 2.Faculty of MedicineAzad UniversityTehranIran
  3. 3.Department of PsychiatryJondi Shapour University of Medical SciencesAhwazIran
  4. 4.Reproductive Biology, Biotechnology and Infertility Research CenterAvesina Research InstituteTehranIran
  5. 5.Department of Neurology, Faculty of MedicineTehran University of Medical SciencesTehranIran

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