The goal of this clinical trial is to learn if benzodiazepines and ECT can treat Catatonic features in Adolescents with Autistic spectrum disorder, it will also learn about Safety and efficacy of benzodiazepines and ECT.

the main questions it aim to answer is if adolescents with profound Autism presenting with catatonic features will show significant improvement on treatment with either benzodiazepines or ECT with no major side effects.

it is an open label pilot study whose participants diagnosed with profound autism presenting with catatonia will receive loading midazolam then maintenance clonazepam daily / ECT sets will be followed up every 2 weeks in 1st month then once / month for next 2 months, observation of symptom improvement will be tracked.

Clinical outcomes will be assessed using the Pediatric Catatonia Rating Scale as the primary outcome measure and the Aberrant Behavior Checklist as a secondary outcome measure. Participants will be followed for three months to evaluate treatment response and safety.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by persistent impairments in social communication and interaction, along with restricted and repetitive patterns of behavior. A subgroup of individuals with ASD meets criteria for profound autism, defined by severe functional impairment requiring continuous supervision, very limited or absent language, and typically a significant intellectual disability (IQ < 50). Adolescents with profound autism often present with severe challenging behaviors, including agitation, aggression, self-injury, and marked functional deterioration.

Catatonia is a complex neuropsychiatric syndrome characterized by a range of psychomotor disturbances such as stupor, mutism, posturing, negativism, agitation, and stereotyped movements. Increasing evidence suggests that catatonia occurs with increased frequency in adolescents and young adults with ASD, particularly those with more severe functional impairment. Catatonic symptoms in individuals with autism may be under-recognized due to overlap with baseline autistic behaviors, leading to delays in diagnosis and treatment.

This open label pilot study aims to explore the presence of catatonic features among Egyptian adolescents with profound autism and to evaluate the efficacy and safety of benzodiazepines and electroconvulsive therapy (ECT) in their management.

The study will be conducted at the Psychiatry and Neurology Center, Tanta University Hospitals, Egypt. Adolescents aged 10 to 19 years with a diagnosis of profound autism attending child and adolescent psychiatry clinics will be screened for catatonic features during the study period. Diagnosis of ASD will be confirmed according to DSM-5 criteria, supported by standardized assessment using the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2), along with documentation of intellectual disability using the Stanford-Binet Intelligence Scales (Fifth Edition).

All eligible participants will undergo comprehensive psychiatric evaluation, medical examination, and standardized assessments, including the Pediatric Catatonia Rating Scale (PCRS) and the Aberrant Behavior Checklist (ABC). Participants who screen positive for catatonia on the PCRS and meet criteria for the intervention phase will be offered a benzodiazepine challenge test using intranasal midazolam.

A positive benzodiazepine challenge is defined as a reduction of at least 50% in catatonic symptoms on the PCRS within 30 minutes of administration. Participants demonstrating a positive response will be treated with oral clonazepam at the lowest effective and tolerated dose and followed for three months, with assessments conducted every two weeks using the PCRS as the primary outcome measure and the ABC as a secondary outcome measure.

Participants who do not show a sufficient response to benzodiazepines will be offered treatment with electroconvulsive therapy (ECT) following caregiver consent. ECT will be administered under general anesthesia using bilateral electrode placement and brief-pulse stimulation. The acute treatment course will consist of two sessions per week for four weeks, followed by continuation treatment once weekly for up to eight weeks in participants demonstrating clinical improvement. Clinical response will be defined as a reduction of at least 50% in PCRS scores. Follow-up assessments will continue biweekly for three months.

Safety monitoring will be conducted throughout the study period, and any adverse events related to benzodiazepines or ECT will be documented. Written informed consent will be obtained from caregivers prior to participation, and all procedures will be conducted in accordance with ethical standards approved by the institutional ethics committee.

This study represents the first investigation of catatonia in adolescents with profound autism in Egypt and the Arab world and aims to contribute to improved recognition and management of this underdiagnosed but treatable condition.

Inclusion Criteria:

• For Screening Group (to identify profound autism and screen for catatonia):

Adolescents aged 10 to 19 years (defined per WHO as the second decade of life). Diagnosis of Autism Spectrum Disorder (ASD) according to DSM-5 criteria, with significant language impairment.

Exceeds diagnostic threshold on the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) Module 1 (for minimal or no speech) OR Module 2 (for phrase speech) AND estimated IQ below 50 on the Stanford-Binet Intelligence Scales, 5th Edition.

For Intervention Group (those proceeding to benzodiazepine challenge ± ECT):

Meets all screening group inclusion criteria. Recent history of severe challenging behaviors (e.g., agitation, aggression, self-injury) refractory to at least two trials of Applied Behavioral Analysis (ABA) AND at least one adequate trial of an antipsychotic medication approved for irritability in ASD (e.g., risperidone or aripiprazole, with sufficient dose and duration).

Screens positive for catatonic features on the Pediatric Catatonia Rating Scale (PCRS; modified Bush-Francis Catatonia Rating Scale for children and adolescents).

Exclusion Criteria:

• Presence of any neurological or medical condition that could affect cognitive or behavioral functioning (e.g., encephalitis, other active neurological diseases, renal failure, hepatic impairment, thyroid disorders, diabetes mellitus, or other uncontrolled systemic illnesses).
• Any contraindication to benzodiazepines (e.g., known hypersensitivity, severe respiratory depression risk) or ECT (e.g., unstable cardiac conditions, intracranial mass, recent stroke, or other standard medical contraindications to anesthesia/general anesthesia).
• Current participation in another interventional clinical trial.
• Caregiver/guardian unwilling or unable to provide informed consent or comply with study procedures.

No plan to share individual participant data (IPD). This is a small, single-site open label pilot study conducted as part of an MD thesis at Tanta University, Egypt, involving a vulnerable population of adolescents with profound autism and catatonia. Due to privacy concerns, small sample size, potential for re-identification, and absence of a dedicated secure data repository or funding for de-identification and controlled access, IPD will not be made available to other researchers. Aggregate results will be published in scientific journals and/or a thesis, and summary data may be shared upon reasonable request to the principal investigator after publication, subject to ethics committee approval and data protection requirements.

This is an open-label study. No masking is used, as all participants, caregivers, and treating clinicians are aware of the interventions administered.