TY - JOUR
T1 - Randomized open-label trial of dextromethorphan in Rett syndrome
AU - Smith-Hicks, Constance L.
AU - Gupta, Siddharth
AU - Ewen, Joshua B.
AU - Hong, Manisha
AU - Kratz, Lisa
AU - Kelley, Richard
AU - Tierney, Elaine
AU - Vaurio, Rebecca
AU - Bibat, Genila
AU - Sanyal, Abanti
AU - Yenokyan, Gayane
AU - Brereton, Nga
AU - Johnston, Michael V.
AU - Naidu, Sakkubai
N1 - Publisher Copyright:
© 2017 American Academy of Neurology.
PY - 2017/10/17
Y1 - 2017/10/17
N2 - Objective: To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome. Methods: We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting. Cognitive data were obtained using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales, while behavioral data were obtained from parent-completed checklists, the Aberrant Behavior Checklist-Community Version, and the Screen for Social Interaction. Anthropometric data were obtained according to the National Health and Nutrition Examination Survey. The Rett Syndrome Severity Scale provided a clinical global impression of the effect of dextromethorphan on clinical severity. Results: Dextromethorphan is safe for use in 3-to 15-year-old girls with Rett syndrome. Thirty-five girls were treated with 1 of 3 doses of dextromethorphan over a period of 6 months. Statistically significant dose-dependent improvements were seen in clinical seizures, receptive language, and behavioral hyperactivity. There was no significant improvement in global clinical severity as measured by the Rett Syndrome Severity Scale. Conclusions: Dextromethorphan is a potent noncompetitive antagonist of the NMDA receptor channel that is safe for use in young girls with Rett syndrome. Preliminary evidence suggests that dextromethorphan may improve some core features of Rett syndrome. Classification of evidence: This study provides Class IV evidence that dextromethorphan at various doses does not change EEG spike counts over 6 months, though precision was limited to exclude an important effect.
AB - Objective: To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome. Methods: We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting. Cognitive data were obtained using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales, while behavioral data were obtained from parent-completed checklists, the Aberrant Behavior Checklist-Community Version, and the Screen for Social Interaction. Anthropometric data were obtained according to the National Health and Nutrition Examination Survey. The Rett Syndrome Severity Scale provided a clinical global impression of the effect of dextromethorphan on clinical severity. Results: Dextromethorphan is safe for use in 3-to 15-year-old girls with Rett syndrome. Thirty-five girls were treated with 1 of 3 doses of dextromethorphan over a period of 6 months. Statistically significant dose-dependent improvements were seen in clinical seizures, receptive language, and behavioral hyperactivity. There was no significant improvement in global clinical severity as measured by the Rett Syndrome Severity Scale. Conclusions: Dextromethorphan is a potent noncompetitive antagonist of the NMDA receptor channel that is safe for use in young girls with Rett syndrome. Preliminary evidence suggests that dextromethorphan may improve some core features of Rett syndrome. Classification of evidence: This study provides Class IV evidence that dextromethorphan at various doses does not change EEG spike counts over 6 months, though precision was limited to exclude an important effect.
UR - http://www.scopus.com/inward/record.url?scp=85031402405&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031402405&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000004515
DO - 10.1212/WNL.0000000000004515
M3 - Article
C2 - 28931647
AN - SCOPUS:85031402405
SN - 0028-3878
VL - 89
SP - 1684
EP - 1690
JO - Neurology
JF - Neurology
IS - 16
ER -