The Use of Medications Approved for Alzheimer’s Disease in Autism Spectrum Disorder: A Systematic Review

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects 1 in 68 children in the United States. Even though it is a common disorder, only two medications (risperidone and aripiprazole) are approved by the U.S. Food and Drug Administration (FDA) to treat symptoms associated with ASD. However, these medications are approved to treat irritability, which is not a core symptom of ASD. A number of novel medications, which have not been approved by the FDA to treat ASD have been used off-label in some studies to treat ASD symptoms, including medications approved for Alzheimer’s disease. Interestingly, some of these studies are high-quality, double-blind, placebo-controlled (DBPC) studies. This article systematically reviews studies published through April, 2014, which examined the use of Alzheimer’s medications in ASD, including donepezil (seven studies, two were DBPC, five out of seven reported improvements), galantamine (four studies, two were DBPC, all reported improvements), rivastigmine (one study reporting improvements), tacrine (one study reporting improvements), and memantine (nine studies, one was DBPC, eight reported improvements). An evidence-based scale was used to rank each medication. Collectively, these studies reported improvements in expressive language and communication, receptive language, social interaction, irritability, hyperactivity, attention, eye contact, emotional lability, repetitive or self-stimulatory behaviors, motor planning, disruptive behaviors, obsessive–compulsive symptoms, lethargy, overall ASD behaviors, and increased REM sleep. Reported side effects are reviewed and include irritability, gastrointestinal problems, verbal or behavioral regression, headaches, irritability, rash, tremor, sedation, vomiting, and speech problems. Both galantamine and memantine had sufficient evidence ranking for improving both core and associated symptoms of ASD. Given the lack of medications approved to treat ASD, further studies on novel medications, including Alzheimer’s disease medications, are needed.

Executive function and functional and structural brain differences in middle‐age adults with autism spectrum disorder

“…Hippocampal differences are particularly salient to the discussion linking ASD and Alzheimer's pathology. Overlap has been observed in genetic risk factors [Khan et al, 2016], amyloid-beta abnormalities [Sokol, Maloney, Long, Ray, & Lahiri, 2011], and cholinergic system involvement, along with efficacy of Alzheimer's drugs in treating ASD symptoms [Rossignol & Frye, 2014]. Conversely, others have hypothesized reduced risk of Alzheimer's disease in adults with ASD due to the hyperplasticity hypothesis [Oberman & Pascual-Leone, 2014].…”

Galantamine alleviates inflammation and insulin resistance in patients with metabolic syndrome in a randomized trial

“…Autonomic nervous system dysfunction with decreased HF and increased LF/HF ratio of HRV have been reported in adolescents with MetS, in addition to metabolic derangements (43). Galantamine and other centrally acting acetylcholinesterase inhibitors have been clinically used in pediatric populations, for instance in children with autism spectrum disorder (44), where galantamine has repeatedly been found to improve core and associated symptoms of the disease (44,45). Importantly, no significant difference in the frequency of side effects between the drug and the placebo arms has been found in a randomized, doubleblind, placebo-controlled study of the effects of galantamine (up to 24 mg/day) for 10 weeks in children with autism, indicating a favorable safety drug profile (45) as we are reporting in this study.…”

Characteristics of Pediatric Exposures to Antidementia Drugs Reported to a Poison Control System

“…2 These medications have also been studied for the treatment of autism, attention deficit hyperactivity disorder, and other psychiatric conditions. 7,8 There is no literature on how frequently antidementia drugs are used for these non-FDA-approved indications. Although serious adverse effects are rarely reported in these typically small studies, these off-label uses may increase further the risk of unintentional pediatric exposures, similar to trends seen with attention deficit hyperactivity disorder medications.…”