Overview
The purpose of this study is to examine the effect of diphenhydramine on sleep in children and adolescents with Autism Spectrum Disorder (ASD). Diphenhydramine is an anti-histaminergic agent with strong hypnotic properties. To accomplish this, the investigators will use a randomized double-blind placebo-controlled crossover 8-week study design to examine the effect of diphenhydramine on sleep physiology as assessed by polysomnography (PSG), actigraphy, circadian rhythm, and clinical measures.
Eligibility
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)
- 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 genetic mutation known to cause autism or intellectual disability (e.g., Fragile X Syndrome), 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 beta-blockers (local or systemic), benzodiazepines, antiepileptic medications, 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 as medications inhibiting CYP2D6
- taking anticholinergic agents (e.g., trihexyphenidyl, thioridazine).