Table 2.

Human studies of lovastatin and simvastatin in neurodevelopmental disorders

Lovastatin
Disorder	Dose	Study type	Results	Reference
FX	Escalating dose 20–40 mg/d 12 weeks	Open-label N = 15 6–31 years	Improvement: aberrant behavior [aberrant behavior checklist (ABC), clinical global impression scale (CGI-S), and vineland adaptive behavior scale] Excessive ERK signaling in platelets	Caku et al. (2014); Pellerin et al. (2016)
FX	10–40 mg/d with PILI 12 weeks	RCT with PILI N = 28 10–17 years	No improvement: language (standardized tests, parent reported visual analogue scale) Behavior (ABC)	Thurman et al. (2020)
NF1	Escalating dose 20–40 mg/d 3 months	Open-label N = 24 10–17 years	Improvement: verbal memory Non-verbal memory Resting state functional connectivity (MRI)	Acosta et al. (2011); Chabernaud et al. (2012)
NF1	200 mg/d 4 d	RCT N = 22 19–31 years	Improvement: intracortical inhibition and synaptic plasticity (transcranial magnetic stimulation), alertness (test of attentional performance)	Mainberger et al. (2013)
NF1	40–80 mg/d 14 weeks	RCT N = 32 10–50 years	Improvement: working memory Declarative memory Verbal fluency Self-reported internalizing No improvement: neural activity (fMRI) Spatial learning (arena maze)	Bearden et al. (2016); Ullrich et al. (2020)
NF1	Escalating dose 20–40 mg/d 16 weeks	RCT N = 146 8–15 years	No improvement: visuospatial learning attention	Payne et al. (2016)
Simvastatin
Disorder	Dose	Study type	Results	Reference
NF1	Dose escalation 10 to 20–40 mg/d 12 weeks	RCT N = 62 8–16 years	No improvement: delayed recall (Rey complex figure test), Attention (cancellation test) Coordinated hand movement (prism adaptation task) Mean brain apparent diffusion coefficient (MRI)	Krab et al. (2008)
NF1	Dose escalation 10 to 20–40 mg/d 12 months	RCT N = 82 8–16 years	No improvement: intelligence (Wechsler intelligence scale) Attention (child and parent behavior checklist) Internalizing behaviors (child and parent behavior checklist)	van der Vaart et al. (2013)
NF1	Dose escalation 30 mg/d 12 weeks	RCT N = 26 4.5–10.5 years	No improvement: hyperactive ERK in platelets GABA in frontal white matter (MR spectroscopy) Resting state fMRI Aberrant behavior (ABC, CGI-S, parent questionnaire)	Stivaros et al. (2018)
Autism	20–40 mg/d as add on to risperidone (1–2 mg/d) 10 weeks	RCT with riperidone N = 70 4–12 years	Improvement: irritability and hyperactivity (ABC)	Moazen-Zadeh et al. (2018)

Lovastatin and simvastatin have been tested in clinical trials for FX and NF1, with varying outcomes.

RCT: randomized placebo-controlled trial; ABC: aberrant behavior checklist, CGI-S: clinical global impression scale, MRI: magnetic resonance imaging, ERK: extracellular-regulated kinase, GABA: γ-Aminobutyric acid.