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Lamotrigine Therapy for Autistic Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial

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Abstract

In autism, glutamate may be increased or its receptors up-regulated as part of an excitotoxic process that damages neural networks and subsequently contributes to behavioral and cognitive deficits seen in the disorder. This was a double-blind, placebo-controlled, parallel group study of lamotrigine, an agent that modulates glutamate release. Twenty-eight children (27 boys) ages 3 to 11 years (M = 5.8) with a primary diagnosis of autistic disorder received either placebo or lamotrigine twice daily. In children on lamotrigine, the drug was titrated upward over 8 weeks to reach a mean maintenance dose of 5.0 mg/kg per day. This dose was then maintained for 4 weeks. Following maintenance evaluations, the drug was tapered down over 2 weeks. The trial ended with a 4-week drug-free period. Outcome measures included improvements in severity and behavioral features of autistic disorder (stereotypies, lethargy, irritability, hyperactivity, emotional reciprocity, sharing pleasures) and improvements in language and communication, socialization, and daily living skills noted after 12 weeks (the end of a 4-week maintenance phase). We did not find any significant differences in improvements between lamotrigine or placebo groups on the Autism Behavior Checklist, the Aberrant Behavior Checklist, the Vineland Adaptive Behavior scales, the PL-ADOS, or the CARS. Parent rating scales showed marked improvements, presumably due to expectations of benefits.

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Authors and Affiliations

  1. The Center for Autism and Related Disorders, Kennedy Krieger Institute, Baltimore, Maryland

    Karin M. Belsito, Karen S. Kirk, Rebecca J. Landa & Andrew W. Zimmerman

  2. Johns Hopkins University Hospital, Baltimore, Maryland

    Paul A. Law, Rebecca J. Landa & Andrew W. Zimmerman

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  1. Karin M. Belsito

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  2. Paul A. Law

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  3. Karen S. Kirk

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  4. Rebecca J. Landa

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  5. Andrew W. Zimmerman

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Belsito, K.M., Law, P.A., Kirk, K.S.et al. Lamotrigine Therapy for Autistic Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.J Autism Dev Disord31, 175–181 (2001). https://doi.org/10.1023/A:1010799115457

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