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Ann Clin Transl Neurol. 2017 Nov 12;4(12):877-887. doi: 10.1002/acn3.494. eCollection 2017 Dec.

Everolimus for treatment of tuberous sclerosis complex-associated neuropsychiatric disorders.

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Division of Neurology Department of Pediatrics Cincinnati Children's Hospital Medical Center University of Cincinnati Cincinnati Ohio.
Department of Psychiatry Boston Children's Hospital and Harvard Medical School Boston Massachusetts.
Division of Child & Adolescent Psychiatry University of Cape Town Cape Town South Africa.
National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda Maryland.
Department of Neurology Boston Children's Hospital Harvard Medical School Boston Massachusetts.
Autism Speaks Boston Massachusetts.
Division of Developmental & Behavioral Pediatrics Department of Pediatrics Cincinnati Children's Hospital Medical Center University of Cincinnati Cincinnati Ohio.



To evaluate if short-term treatment with everolimus was safe and could improve neurocognition and behavior in children with TSC.


This was a prospective, double-blind randomized, placebo-controlled two-center phase II study. Participants diagnosed with TSC and age 6-21 years were treated with 4.5 mg/m2 per day of oral everolimus (n = 32) or matching placebo (n = 15) taken once daily for 6 months. For efficacy, a comprehensive neurocognitive and behavioral evaluation battery was performed at baseline, 3 months, and 6 months. For safety, adverse events recorded continuously via patient diary were categorized and graded per NCI Common Toxicity Criteria for Adverse Events, version 3.0 (CTCAE 3.0). Analyses were performed on the intention-to-treat population (n = 47).


Nearly all assessment measures failed to demonstrate significant differences between the two groups at the end of 6 months. Only one measure each of executive function (Cambridge Neuropsychological Test Automated Battery Stockings of Cambridge) favoring placebo (P = 0.025) and social cognition (Social Responsiveness Scale Social Cognition Subscale) favoring everolimus (P = 0.011) was observed. A total of 473 adverse events (AE) were reported. The average number of total AE per subject was similar for both placebo and everolimus. Most were mild or moderate in severity and serious AE were rare.


While safe, oral everolimus administered once daily for 6 months did not significantly improve neurocognitive functioning or behavior in children with TSC.

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