Skip to main content
SpringerLink
Log in

High-Dose Pyridoxine and Magnesium Administration in Children with Autistic Disorder: An Absence of Salutary Effects in a Double-Blind, Placebo-Controlled Study

  • Published:
Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

Several reports have described salutary effects such as decreased physical aggression and improved social responsiveness being associated with the administration of high doses of pyridoxine and magnesium (HDPM) in open-labeled and controlled studies of patients with autism. Despite this fact, this intervention remains controversial. A 10-week double-blind, placebo-controlled trial was undertaken to examine both the efficacy and safety of HDPM in autism. Twelve patients were enrolled, and 10 patients (mean age 6 years 3 months) were able to complete the study. HDPM at an average dose of 638.9 mg of pyridoxine and 216.3 mg of magnesium oxide was ineffective in ameliorating autistic behaviors as assessed by the Children's Psychiatric Rating Scale (CPRS), the Clinical Global Impression Scale, and the NIMH Global Obsessive Compulsive Scale. Furthermore, no clinically significant side effects were noted during HDPM administration. A trend for a transient change on the CPRS was found that was possibly due to a placebo response. This study raises doubts about the clinical effectiveness of HDPM in autistic disorder.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  • Aman, M. G., Van Bourgondien, M. E., Wolford, P. L., & Sarphare, G. (1995). Psychotropic and anticonvulsant drugs in subjects with autism: Prevalence and patterns of use. Journal of the American Academy of Child and Adolescent Psychiatry, 34, 1672–1681.

    Google Scholar 

  • American Academy of Pediatrics, Committee on Nutrition. (1976). Megavitamin therapy for childhood psychoses and learning disabilities. Pediatrics, 58, 910–912.

    Google Scholar 

  • American Psychiatric Association. (1987). Diagnostic and statistical manual of mental disorders (3rd ed., rev.). Washington DC: Author.

    Google Scholar 

  • Anderson, L. T., Campbell, M., Grega, D. M., Perry, R., Small, A. M., & Green, W. H. (1984). Haloperidol in the treatment of infantile autism: Effects on learning and behavioral symptoms. American Journal of Psychiatry, 141, 1195–1202.

    Google Scholar 

  • Campbell, M., & Palij, M. (1985). Behavioral and cognitive measures used in psychopharmacologic studies of infantile autism. Psychopharmacology Bulletin, 21, 1047–1053.

    Google Scholar 

  • Campbell, M., Anderson, L. T., Small, A. M., Adams, P., Gonzalez, N. M., & Ernst, M. (1993). Naltrexone in autistic children: Behavioral symptoms and attentional learning. Journal of the American Academy of Child and Adolescent Psychiatry, 32, 1283–1291.

    Google Scholar 

  • Coleman, M., Steinberg, G., Tippett, J., Bhagavan, H. N., Coursin, D. B., Gross, M., Lewis, C., & DeVeau, L. (1979). A preliminary study of the effect of pyridoxine administration in a subgroup of hyperkinetic children: A double-blind crossover comparison with methylphenidate Biological Psychiatry, 14, 741–751.

    Google Scholar 

  • DeVeaugh-Geiss, J., Moroz, G., Biederman, J., Cantwell, D., Fontaine, R., Greist, J. H., Reichler, R., Katz, R., & Landau, P (1992). Clomipramine hydrochloride in childhood and adolescent obsessive-compulsive disorder—a multicenter trial. Journal of the American Academy of Child and Adolescent Psychiatry, 31, 45–49.

    Google Scholar 

  • DiLalla, D. L., & Rogers, S. J. (1994). Domains of the Childhood Autism Rating Scale: Relevance for diagnosis and treatment. Journal of Autism and Developmental Disorders, 24, 115–128.

    Google Scholar 

  • Dolske, M. C., Spollen, J., McKay, S., Lancashire, E., & Tolbert, L. (1993). A preliminary trial of ascorbic acid as supplemental therapy for autism. Progress in Neuropsychopharmacology and Biological Psychiatry, 17, 765–774.

    Google Scholar 

  • Eisenberg, D. M., Kessler, R. C., Foster, C., Norlock, F. E., Calkins, D. R., & Delbanco, T. L. (1993). Unconventional medicine in the United States. New England Journal of Medicine, 328, 246–252.

    Google Scholar 

  • Ernst, M., Devi, L., Silva, R. R., Gonzalez, N. M., Small, A. M., Malone, R. P, & Campbell, M. (1993). Plasma beta-endorphin levels, naltrexone, and haloperidol in autistic children. Psychopharmacology Bulletin, 29, 221–227.

    Google Scholar 

  • Frankhauser, M. P., Karumanchi, V. C., German, M. L., Yates, A., & Karumanchi, S. D. (1992). A double-blind, placebo-controlled study of the efficacy of transdermal clonidine in autism. Journal of Clinical Psychiatry, 53, 77–82.

    Google Scholar 

  • Gillberg, C., Wahlstrom, J., Johansson, R., Tornblom, M., Albertson-Wikland, K. (1986). Folic acid as an adjunct in the treatment of children with the autism fragile-X syndrome (AFRAX). Developmental Medicine & Child Neurology, 28, 624–627.

    Google Scholar 

  • Gonzalez, N. M., Campbell, M., Small, A. M., Shay, J., Bluhm, L. D., Adams, P. B., & Foltz, R. L. (1994). Naltrexone plasma levels, clinical response and effect on weight in autistic children. Psychopharmacology Bulletin, 30, 203–208.

    Google Scholar 

  • Gordon, C. T., Rapoport, J. L., Hamburger, S. D., State, R. C., & Mannheim, G. B. (1992). Differential response of seven subjects with autistic disorder to clomipramine and desipramine. American Journal of Psychiatry, 149, 363–366.

    Google Scholar 

  • Gordon, C. T., State, R. C, Nelson, J. E., Hamburger, S. D., & Rapoport, J. L. (1993). A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Archives of General Psychiatry, 50, 441–447.

    Google Scholar 

  • Goyette, C. H., Conners, C. K., & Ulrich, R. F. (1978). Normative data on revised Conners parent and teacher rating scales. Journal of Abnormal Child Psychology, 6, 221–236.

    Google Scholar 

  • Hanning, R. M., & Zlotkin, S. H. (1985). Unconventional eating practices and their health implications. Pediatric Clinics of North America, 32, 429–445.

    Google Scholar 

  • Insel, T. R., Murphy, D. L., Cohen, R. M., Alterman, I., Kilts, C., & Linnoila, M. (1983). Obsessive-compulsive disorder: A double-blind trial of clomipramine and clorgyline. Archives of General Psychiatry, 40, 605–612.

    Google Scholar 

  • Jakobs, C., Jaeken, J., & Gibson, K. M. (1993). Inherited disorders of GABA metabolish. Journal of Inherited Metabolic Disease, 16, 704–715.

    Google Scholar 

  • Jaselskis, C. A., Cook, E. H., Jr., Fletcher, K. E., & Leventhal, B. L. (1992). Clonidine treatment of hyperactive and impulsive children with autistic disorder. Journal of Clinical Psychopharmacology, 12, 322–327.

    Google Scholar 

  • Kolmen, B. K., Feldman, H. M., Handen, B. L., & Janosky, J. E. (1995). Naltrexone in young autistic children; A double-blind, placebo-controlled crossover study. Journal of the American Academy of Child and Adolescent Psychiatry, 34, 223–231.

    Google Scholar 

  • Lelord, G., Muh, J. P., Barthelemy, C., Martineau, J., Garreau, B., & Callaway, E. (1981). Effects of pyridoxine and magnesium on autistic symptoms-initial observations. Journal of Autism and Developmental Disorders, 11, 219–230.

    Google Scholar 

  • Leventhal, B. L, Cook, E. H., Jr., Morford, M., Ravitz, A. J., Heller, W., & Freedman, D. X. (1993). Clinical and neurochemical effects of fenfluramine in children with autism. Journal of Neuropsychiatry and Clinical Neurosciences, 5, 307–315.

    Google Scholar 

  • Martineau, J., Barthelemy, C., Gareau, B., & Lelord, G. (1985). Vitamin B6, magnesium, and combined B6-Mg: Therapeutic effects in childhood autism. Biological Psychiatry, 20, 467–478.

    Google Scholar 

  • Martineau, J., Barthelemy, C., & Lelord, G. (1986). Long-term effects of combined vitamin B6-magnesium administration in an autistic child. Biological Psychiatry, 21, 511–518.

    Google Scholar 

  • Martineau, J., Barthelemy, C., Cheliakine, C., & Lelord, G. (1988). Brief report: An open middle-term study of combined vitamin B6-magnesium in a subgroup of autistic children selected on their sensitivity to this treatment. Journal of Autism and Developmental Disorders, 18, 435–447.

    Google Scholar 

  • McLachlan, R. S., & Brown, W. F. (1995). Pyridoxine dependent epilepsy with iatrogenic sensory neuronopathy. Canadian Journal of Neurologic Sciences, 22, 50–51.

    Google Scholar 

  • Menage, P., Thibault, G., Barthélèmy, C., Lelord, G., & Bardos, P. (1992). CD4+CD45RA+T lymphocyte deficiency in autistic children: Effect of a pyridoxine-magnesium treatment. Brain Dysfunction, 5, 326–333.

    Google Scholar 

  • National Institute of Mental Health. (1985). Clinical Global Impression Scale. Psychopharmacology Bulletin, 21, 839–843.

    Google Scholar 

  • Overall, J. E., & Campbell, M. (1988). Behavioral assessment of psychopathology in children: Infantile autism. Journal of Clinical sychology, 44, 708–716.

    Google Scholar 

  • Pauling, L. (1974). On the orthomolecular environment of the mind: Orthomolecular theory. American Journal of Psychiatry, 131, 1251–1257.

    Google Scholar 

  • Pfeiffer, S. I., Norton, J., Nelson, L., & Shott, S. (1995). Efficacy of vitamin B6 and magnesium in the treatment of autism: A methodology review and summary of outcomes. Journal of Autism and Developmental Disorders, 25, 481–493.

    Google Scholar 

  • Quintana, H., Birmaher, B., Stedge, D., Lennon, S., Freed, J., Bridge, J., & Greenhill, L. (1995). Use of methylphenidate in the treatment of children with autistic disorder. Journal of Autism and Developmental Disorders, 25, 283–294.

    Google Scholar 

  • Rimland, B. (1988). Controversies in the treatment of autistic children: Vitamin and drug therapy. Journal of Child Neurology, 3(Suppl), S68–S72.

    Google Scholar 

  • Rimland, B., Callaway, E., & Dreyfus, P. (1978). The effect of high doses of vitamin B6 on autistic children: A double-blind crossover study. American Journal of Psychiatry, 135, 472–475.

    Google Scholar 

  • Schaumberg, H., Kaplan, J., Windebank, A., Vick, N., Rasmus, S., Pleasure, D., & Brown, M. J. (1983). Sensory neuropathy from pyridoxine abuse: A new megavitamin syndrome. New England Journal of Medicine, 309, 445–448.

    Google Scholar 

  • Schopler, E., Reichler, R., DeVellis, R., & Daly, K. (1980). Toward objective classification of childhood autism: Childhood autism rating scale (CARS). Journal of Autism and Developmental Disorders, 10, 91–103.

    Google Scholar 

  • Schulz, K. F., Chalmers, I., Hayes, R. J., & Altman, D. G. (1995). Empiric evidence of bias: Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. Journal of the American Medical Association, 273, 408–412.

    Google Scholar 

  • Spigelblatt, L., Laine-Ammara, G., Pless, B., & Guyver, A. (1994). The use of alternative medicine by children. Pediatrics, 94, 811–814.

    Google Scholar 

  • Tolbert, L., Haigler, T., Waits, M. M., & Dennis, T. (1993). Brief report: Lack of response in an autistic population to a low dose clinical trial of pyridoxine and magnesium. Journal of Autism and Developmental Disorders, 23, 193–199.

    Google Scholar 

  • Willemsen-Swinkels, S. H. N., Buitelaar, J. K., Nijhof, G. J., & van Engeland, H. (1995). Failure of naltrexone hydrochloride to reduce self-injuries and autistic behavior in mentally retarded adults: Double-blind placebo-controlled studies. Archives of General Psychiatry, 52, 766–773.

    Google Scholar 

  • Wolraich, M. L., Wilson, D. B., & White, J. W. (1995). The effect of sugar on behavior or cognition in children: A meta-analysis. Journal of the American Medical Association, 274, 1617–1621.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Case Western Reserve University and University Hospitals of Cleveland, USA

    Robert L. Findling & Max Wiznitzer

  2. University Hospitals of Cleveland, USA

    Kathleen Maxwell & Lynette Scotese-Wojtila

  3. Case Western Reserve University, USA

    Jie Huang & Toyoko Yamashita

Authors
  1. Robert L. Findling
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathleen Maxwell
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lynette Scotese-Wojtila
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Toyoko Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Max Wiznitzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Findling, R.L., Maxwell, K., Scotese-Wojtila, L. et al. High-Dose Pyridoxine and Magnesium Administration in Children with Autistic Disorder: An Absence of Salutary Effects in a Double-Blind, Placebo-Controlled Study. J Autism Dev Disord 27, 467–478 (1997). https://doi.org/10.1023/A:1025861522935

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1025861522935

Keywords

Search

Navigation