Trial of Diphenhydramine for Sleep in Children With Autism

Inclusion criteria: Participants will meet the following * Outpatients between 8 and 17 years of age at the time of consent * Diagnostic and Statistical Manual, 5th edition (DSM-5) criteria for Autism Spectrum Disorder (ASD) on the basis of clinical evaluation, confirmed with the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule, 2nd Ed (ADOS-2) or the Childhood Autism Rating Scale, Second Edition (CARS-2). * Males and females * Availability of polysomnography (PSG) or actigraphy data * Sleep disturbances as assessed using Children's Sleep Habits Questionnaire (CSHQ) with a score of 41 or higher * care provider who can reliably bring participant to clinic visits, provide trustworthy ratings, and interacts with participant on a regular basis * stable medications for at least 2 weeks, with the exception of Prozac which is required to be stable for at least 4 weeks * no planned changes in psychosocial and biomedical interventions during the trial * willingness to provide additional saliva samples and participate in key study procedures (i.e., safety measurements every visit, PSG at weeks 4 and 8, and wear the actigraphy watch for 2 weeks before the beginning of trial as well as during the 8 weeks of the trial). Exclusion criteria: Participants will be excluded if one or more of the following is met * active suicidal ideation or DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or psychotic disorder * active medical problems: migraine, asthma, seizure disorder, significant physical illness (e.g., anaphylaxis, serious liver, renal, or cardiac pathology) * evidence of a metabolic, or infectious etiology for the participant's autism on the basis of medical history, neurologic history, and available tests for inborn errors of metabolism and chromosomal analysis * pregnant or sexually active females not using a reliable method of contraception (urinary tests for pregnancy will be employed in this study) * individuals taking benzodiazepines, antiepileptic medications when prescribed for seizure disorder/epilepsy, melatonin and centrally-acting antihistamines * history of hypersensitivity to diphenhydramine * history of severe side effects from diphenhydramine * history of adequate trial of diphenhydramine * current use of any medications known to interact with diphenhydramine such as medications inhibiting CYP2D6 * taking anticholinergic agents (e.g., trihexyphenidyl, thioridazine).