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 SpectrumDisorder (ASD) on the basis of clinical evaluation, confirmed with the AutismDiagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule, 2nd Ed (ADOS-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, providetrustworthy ratings, and interacts with participant on a regular basis

• stable medications for at least 2 weeks, with the exception of Prozac which isrequired 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 studyprocedures (i.e.,safety measurements every visit, PSG at weeks 4 and 8, and wear theactigraphy watch for 2 weeks before the beginning of trial as well as during the 8weeks 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, schizoaffectivedisorder, or psychotic disorder

• active medical problems: migraine, asthma, seizure disorder, significant physicalillness (e.g., anaphylaxis, serious liver, renal, or cardiac pathology)

• evidence of a genetic mutation known to cause autism or intellectual disability (e.g., Fragile X Syndrome), metabolic, or infectious etiology for the participant'sautism on the basis of medical history, neurologic history, and available tests forinborn 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 beta-blockers (local or systemic), benzodiazepines, antiepilepticmedications, melatonin and 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 asmedications inhibiting CYP2D6

• taking anticholinergic agents (e.g., trihexyphenidyl, thioridazine).