Autism Treatment. Evidence-Based Medicine

Autism, or autism spectrum disorder (ASD), is a group of complex neurodevelopmental conditions that appear in early childhood as difficulties with social interaction and communication, along with restricted interests or repetitive behavior. Over the past 20 years, there has been significant progress in understanding the biological basis of autism and in developing approaches to its treatment. Although there is currently no universal "cure" for autism, evidence-based medicine has developed a number of methods that can improve patients' condition, especially when intervention starts early. This report reviews modern clinical studies, Nobel Prize discoveries and documented cases of therapy for ASD over the past 20 years. Particular attention is paid to methods whose effectiveness is supported by evidence-based medicine, including behavioral interventions, medication therapy, genetic and stem cell approaches, as well as some alternative methods. Based on this analysis, detailed recommendations and a treatment protocol have been formulated for practical use at CSM Clinic, with step-by-step implementation of measures, the necessary resources, conclusions, and an outlook on the future development of autism therapy.

Major Achievements of the Past 20 Years in Autism Research

Over the past two decades, breakthroughs have changed the scientific approach to autism. The use of new technologies, such as molecular genetics, induced pluripotent stem cells, and genome editing, has made it possible to better understand the biological basis of ASD and opened the way to future targeted therapies. Several Nobel Prize achievements that directly or indirectly influenced autism research deserve special mention:

• Molecular neurobiology of synapses. Thomas Südhof, the 2013 Nobel laureate, was recognized for uncovering the mechanisms of synaptic transmission. His research on neurexins and neuroligins, molecules involved in synaptic function, revealed their link to genetic forms of autism. This work highlighted that disruption of delicate synaptic processes may underlie selective (non-global) deficits in ASD. Current studies continue to clarify how mutations in these genes lead to autistic traits and to look for ways to influence synaptic function pharmacologically.
  
• Induced pluripotent stem cells (iPSCs). The 2012 Nobel Prize discovery (Shinya Yamanaka) of creating induced pluripotent stem cells from skin cells made it possible to "grow" neurons of people with autism in the laboratory. This provided a unique model for studying brain development in autism and testing potential drugs in vitro. For example, researchers can obtain neurons from the skin cells of a child with autism and observe abnormalities in the development of nervous tissue, which was not previously possible directly. Such "mini-brains" (organoids) help identify pathophysiological processes and select molecules that correct them.
  
• CRISPR-Cas9 gene editing. The 2020 Nobel Prize for CRISPR technology opened the possibility of precise genome editing. Although it is still an experimental tool, in the future CRISPR may be used to correct monogenic forms of autism (for example, mutations that cause Rett syndrome or Angelman syndrome). Already, in animal models this method allows candidate genes to be "switched off" or corrected, testing whether behavior normalizes. This lays the foundation for future gene therapies for autism, especially in cases where a specific genetic cause is known.
  

Besides the Nobel milestones, large-scale genetic studies by consortia (AGP, the Simons Foundation Autism Research Initiative, and others) were also important; they identified hundreds of ASD susceptibility genes. This confirmed that autism is not a single disease but a spectrum of conditions with diverse biological pathways. This understanding led to the concept of precision medicine in autism: instead of a universal approach, the focus is on individualized interventions selected for the specific profile of the child (genetic, metabolic, neurophysiological).

Finally, over 20 years the paradigm of autism clinical research has also changed. Whereas previously most interventions were based on behavioral observations, they are now developed on the basis of scientific data about the brain. At the same time, attention to early detection and intervention has grown: numerous studies have shown that starting therapy in the first years of life may significantly improve outcomes. In the following sections, we will review specific autism treatment methods whose effectiveness is supported by modern evidence.

Overview of Effective Autism Treatment Methods

There is a wide range of therapeutic approaches to autism, from behavioral and educational programs to medication treatment and experimental biomedical interventions. Below is an analysis of the main methods, including their description, the scientific evidence for their effectiveness, and an assessment of their impact on patients' condition. For a summary, Table 1 gives a brief overview of these approaches and the level of their effectiveness.

Table 1. Main approaches to ASD treatment and their effectiveness (2005-2025)

As Table 1 shows, the strongest evidence of effectiveness for improving the development of children with autism is seen for early intensive behavioral interventions and some medication approaches for managing accompanying symptoms. Behavioral therapy is the cornerstone: although it does not completely "cure" autism, it can significantly modify its manifestations and help a child acquire skills for as independent a life as possible. Medication therapy plays a supporting role, relieving acute problems and stabilizing the condition, which allows educational programs to be carried out more effectively. Genetic and stem cell methods are still at the research stage: they are very promising but need more evidence before they become part of the standard of care. Alternative methods may give isolated improvements as support for the main treatment, but overall their evidence base is limited and they do not replace proven approaches.

Next, we will look at how this knowledge can be put into practice as a treatment protocol for clinical practice.

Recommendations and Autism Treatment Protocol for Doctors (CSM Clinic)

Based on the analysis above, a comprehensive protocol for managing patients with autism has been developed for implementation at CSM Clinic. The protocol provides for a multidisciplinary approach, step-by-step care, and involvement of the family. Below are the main components of the protocol, the stages of its implementation, and the resources needed for successful treatment.

Early Diagnosis and Needs Assessment

Goal of the stage: to confirm the ASD diagnosis using standardized tools, assess the child's strengths and problem areas, identify coexisting medical conditions, and determine the baseline level of development for further therapy planning.

Steps and measures:

• History taking and observation. The first visit includes a detailed interview with the parents (developmental history, family history) as well as structured observation of the child's behavior. It is advisable to use validated screening questionnaires (M-CHAT-R/F for children aged 16-30 months, or AQ for older ones) and developmental scales.
• Standardized diagnostics. When ASD is suspected, an assessment is carried out using "gold standard" tools, for example ADOS-2 (Autism Diagnostic Observation Schedule) for direct assessment of communication and social interaction, and ADI-R (Autism Diagnostic Interview) with the parents. This provides reliable confirmation of the diagnosis and determination of the level of functioning (for example, whether there is coexisting intellectual disability, language skills, and so on).
• Medical examination for coexisting conditions. This includes examination by a neurologist and a pediatrician. Audiological screening is mandatory (to rule out hearing impairment, which can mimic the speech symptoms of autism). When indicated, a consultation with a child psychiatrist. Laboratory tests: genetic testing (chromosomal microarray analysis (CMA) to detect microdeletions/duplications; testing for fragile X syndrome). Identifying the cause may influence treatment tactics (for example, a specific diet in metabolic diseases). It is also worth checking blood lead levels (in case of pica), thyroid function, and vitamin D, to correct any abnormalities.
• Assessment of behavior and skills. Use of scales to measure the severity of autistic manifestations and adaptive skills: CARS (Childhood Autism Rating Scale), ABC (Autism Behavior Checklist), Vineland Adaptive Behavior Scales (assessment of social and daily living skills). This allows the baseline to be quantified, from which progress is then measured.
• Comorbid disorders. Examination for epileptic seizures (an EEG if suspected), sleep disorders (questionnaires and, if needed, polysomnography), gastrointestinal problems (a gastroenterologist consultation for chronic constipation or diarrhea), assessment of attention and hyperactivity (ADHD criteria), and so on.

Result of the stage: a formulated, confirmed diagnosis (for example, "ASD without intellectual impairment" or "ASD with intellectual disability"), a profile of the child's strong and weak skills, and a list of coexisting medical problems. On this basis, the team of specialists, together with the family, develops an individual therapy plan. Already at this stage it is important to give parents initial informational support: to explain the nature of autism, the prognosis, and the options for interventions, and to involve them in active cooperation.

Developing an Individual Intervention Program

Goal of the stage: to draw up a detailed plan of therapeutic measures selected for the needs of the particular child, define priority goals, and distribute roles among the specialists. The plan should be long-term (for the next 1-2 years), broken down into short-term goals (for example, for the next 3-6 months).

Team: multidisciplinary: a doctor (neurologist or psychiatrist), a psychologist/behavior therapist, a special education teacher (defectologist), a speech therapist, an occupational therapist (a skills development specialist), and, if needed, a physical therapist. Coordination is carried out by a lead specialist (case manager) who stays in contact with the family.

Program components:

• Behavioral therapy (ABA / ESDM). This is the foundation. It is recommended to start intensive sessions using applied behavior analysis as early as possible (ideally before the age of 3-4 years). The optimal intensity is 20-40 hours per week of individual sessions with a therapist, plus additional learning situations at home with the parents' participation. If CSM Clinic has its own ABA therapists, sessions should be scheduled daily. If not, cooperation should be set up with applied behavior therapy centers, providing a referral for the patient and follow-up. For the youngest children (under 3 years), the comprehensive ESDM model, which combines behavioral principles with development in natural play settings, has proven itself well; it can be implemented as home sessions after training the parents with a specialist's participation. Specific goals of the ABA program are defined: for example, to teach pointing with a gesture instead of pulling an adult's hand; to teach the skill of eating independently with a spoon; to reduce the number of self-stimulation episodes, and so on. Goals should be SMART (specific, measurable, achievable, relevant, time-bound).
• Speech and communication therapy. Depending on the level of speech, a speech therapist is involved. If the child is nonverbal, alternative communication is taught (PECS cards, sign language). For children with speech, the focus is on developing an active vocabulary, phrase speech, and dialogue skills. The speech therapist works individually 2-3 times a week.
• Development of social skills. If the child attends a preschool or school, coordination with teachers regarding inclusive education. For younger children, inclusion in group sessions with peers (small groups of 2-3 children with ASD and neurotypical children, supervised by a psychologist), where play skills, turn-taking, and joint activity are practiced. For teenagers with high-functioning autism, social-communication training (at the clinic or with an invited trainer), where communication situations are modeled, along with learning about friendship, understanding humor, and independent living skills.
• Sensory integration and occupational therapy. A sensory integration specialist assesses which of the child's sensory systems are hyper- or hyposensitive (for example, tactile defensiveness, sound sensitivity, balance problems). In sessions in a specially equipped sensory room (swings, balls, textures, brushes), the specialist helps the child gradually adapt to different sensations. This may reduce anxiety and improve behavior in everyday life. The occupational therapist teaches self-care, fine motor skills, and age-appropriate daily activities.
• Parent involvement (parent training). Teaching parents the principles of interacting with the child is a mandatory element. The clinic can organize training sessions for parents (for example, the "Early Bird" program or modular trainings). Parents are taught techniques for encouraging desired behavior, managing tantrums, and developing speech in everyday situations. Psychological support for the family is also important: if needed, consultations with a family psychologist and support groups for parents of children with ASD, which the clinic can hold monthly. Active involvement of the family may considerably improve the success of interventions.

Documenting the protocol: Each component of the program is documented in detail: who is responsible, how many hours per week, and what the goals are. For example, "ABA therapy: 20 hours/week, therapist A.B., goals: teach joint attention, reduce screaming during frustration"; "Speech therapist: 3 hours/week, developing understanding of everyday instructions"; "Sensory sessions: 2 times/week, 45 minutes each". Such an individual plan is approved by the team and the parents and is reviewed every 3-6 months.

Medication Treatment of Accompanying Symptoms

Goal of the stage: to improve the child's medical and mental condition by reducing symptoms that interfere with learning and socialization (aggression, self-injury, severe anxiety, hyperactivity, epileptic seizures, and so on). Medication therapy is prescribed only after a detailed assessment of benefits and risks and when non-drug measures have been ineffective for the specific problem.

Main indications and recommendations:

• Severe irritability, aggression, self-injurious behavior. If a child has frequent uncontrolled tantrums with aggression, attacks on others, or hitting themselves, and this cannot be managed by behavioral methods, risperidone or aripiprazole are the drugs of choice. Start with low doses (risperidone 0.25-0.5 mg/day depending on weight, titrating gradually). Monitoring of side effects: weight monthly, glucose and lipids every 3 months, assessment of extrapyramidal symptoms. The goal is to reduce the intensity of aggression by at least 50%. After control is achieved, continue therapy for at least 6 months, then consider a gradual dose reduction under monitoring of the child's condition.
• Hyperactivity, attention deficit, impulsivity. With comorbid ADHD or marked inattention that prevents the child from sitting through sessions, a psychostimulant may be tried. The most data are available for methylphenidate (an extended-release form, for example 5-10 mg in the morning). In some children with autism, stimulants are less effective than in typical ADHD, but about 50% show improved attention and reduced hyperactivity. Possible side effects (increased anxiety, irritability at the end of the day, reduced appetite) should be monitored closely. Alternatively, the non-stimulant drug atomoxetine (a norepinephrine reuptake inhibitor) can be considered; its effect on attention develops more slowly (4-6 weeks).
• Anxiety, obsessive states, depressive mood. In younger children, it is preferable to address such states with psychological methods (daily schedule, sensory breaks, psychotherapy). However, teenagers with autism and high intelligence often develop anxiety disorders or depression as they become aware of their difficulties. In such cases, an SSRI may be prescribed (for example, sertraline, starting with minimal doses of about 12.5-25 mg/day). There are data on improved social initiative and reduced repetitive behavior in some teenagers on SSRIs, but overall the effects vary. A gradual dose increase and monitoring for paradoxical worsening are important (increased excitability is possible in some children when starting an SSRI). Tricyclic antidepressants (for example, clomipramine) have also been studied and show some effectiveness, but they are rarely used because of their side effect profile.
• Sleep disorders. Sleep problems are very common in ASD. First, sleep hygiene is introduced: a stable routine, no gadgets before bed, bedtime rituals. If this does not help, melatonin (3-5 mg 30 minutes before bedtime) is a safe and effective option. Studies have shown shorter sleep onset time and longer sleep duration on melatonin compared with placebo, without serious side effects. Other agents (for example, antihistamines as sleep aids, or clonidine) can be considered, but melatonin is generally effective.
• Epilepsy. In about 20-30% of children with autism, epilepsy or epileptiform EEG activity is present. Treatment is carried out by a neurologist according to standard protocols with antiepileptic drugs (valproate, levetiracetam, and others, depending on the type of seizures). Seizure control indirectly supports better cognitive development.
• Gastrointestinal problems. Chronic constipation or abdominal pain can worsen behavior. Treatment depends on the cause: a high-fiber diet, laxatives, or a gluten-free diet if sensitivity is found (taking into account the potential benefit of diets described above).

Note: all prescriptions are made in the context of comprehensive therapy. For example, if risperidone is started to control aggression, a behavior therapist works in parallel on alternative self-regulation strategies. The aim is to use the minimum effective dose of medication and, where possible, to withdraw it gradually once stabilization is achieved. Doctors at CSM Clinic should regularly (at least once every 1-3 months) assess symptom dynamics with scales (for example, ABC, the Irritability subscale) and side effects (a side effect checklist). This information is discussed with the parents, and doses are adjusted or the drug is changed as indicated.

Monitoring Progress and Adjusting the Program

Goal of the stage: to track the effectiveness of the interventions and the achievement of the set goals, and to adapt the individual plan as the child grows and their needs change.

Approaches:

• Regular team meetings. Every 3 months, the clinic's multidisciplinary team (all the specialists involved) meets to discuss the patient's progress. Achievements are analyzed: which goals were met (for example, "the child learned to point at objects, as planned"), which were not, and the reasons for the difficulties are clarified. Parents are always present and give feedback: what they notice at home and what their main concerns are right now. Based on this, goals for the next period are adjusted.
• Objective measurements. Repeat testing with some scales one year after the start of the program: for example, reassessing adaptive skills (Vineland) and the level of autistic symptoms (CARS or ADOS), and comparing with the baseline. This gives a quantitative indicator of progress. Of course, not all changes can be captured by tests, but a trend (lower CARS scores, improved IQ or language) will confirm the success of therapy.
• Flexibility of interventions. Based on monitoring, the emphasis of the program may change. For instance, if the child has significantly improved language comprehension and started saying individual words, the speech therapist increases the focus on developing phrase speech; if sensory hypersensitivity has decreased, more attention can be given to social skills in a group. When certain skills are achieved, some therapies may be scaled back or reduced in intensity: for example, ABA hours may be reduced from 30 to 15 hours/week if the child has started school and receives partial support there. Conversely, new elements may be added: in adolescence, career guidance and independent living training (cooking, using public transport, and so on). Every transition period (school, puberty) is accompanied by a reassessment of needs.
• Documenting progress. The clinic keeps a detailed log or electronic patient record, which records all interventions and their results. This is important both for subsequent doctors and for the family (who can receive a discharge summary with recommendations).

Monitoring also includes an assessment of parent satisfaction: their opinion about which methods helped most and which did not, and what they would like to change. A high level of cooperation with the family and a protocol that adapts to real-life conditions are key to long-term success.

Resources and Organization of the Process at the Clinic

To implement the protocol described above, CSM Clinic needs to provide the appropriate resources:

• Staffing. The staff should include (or be able to bring in for consultation) a child psychiatrist or neurologist, a clinical psychologist, several applied behavior analysts (ABA specialists) and behavior therapists, a speech therapist, an occupational therapist, a sensory integration specialist, and a social educator. If in-house specialists are insufficient, cooperation should be established with external centers and specialists who can come to the clinic on a schedule or see patients on referral. It is also desirable to have a nurse or coordinator responsible for organizing visits, reminding families, and so on.
• Facilities and equipment. Rooms for individual therapy, equipped with play materials and a table and chair for one-on-one sessions. A separate sensory room: a mat, a swing, balls, brushes for tactile stimulation, and lighting equipment for sensory integration sessions. A speech therapy room with materials for speech development (cards, a mirror, toy objects for naming). Educational toys and materials: puzzles, sorters, cards, and developmental games for different age levels. Computers or tablets with special programs for children with autism (for teaching communication and social situations).
• Methodological support. Protocols, checklists for assessing behavior, intervention plan forms, and observation logs. Standardized questionnaires and tests (ADOS, CARS, Vineland, etc.): the clinic must acquire them and train specialists to use them. Literature and guides for specialists on the methods (ABA manuals, ESDM guides, and other current guidelines).
• Staff training. Regular professional development: training in applied behavior analysis (BCBA certification for lead analysts), seminars on new methods, and participation in professional conferences. The team should be familiar with the latest evidence-based practices. For example, a specialist from a leading center could be invited to give a master class on early intervention.
• Interagency cooperation. The clinic should establish contact with special schools, rehabilitation centers, and early intervention services in the region. This is needed so that the child's transition, for example to kindergarten or school, is smooth, with recommendations passed on to teachers and inclusion planned jointly. Cooperation with nongovernmental organizations and foundations that support families with autism is also important for comprehensive help (legal, social) beyond the medical component.

Organizationally, the protocol can be implemented in stages: first launch a pilot project for a small number of patients, work out the team's interaction, and collect feedback. Then expand to a larger number of children. It is important to keep statistics on the clinic's results: the percentage of children who achieved improvement and the average changes in measures. This will make it possible to evaluate the effectiveness of CSM's work and make changes if needed.

Conclusions and Outlook

Conclusions. The analysis of clinical studies from the past 20 years confirms that although autism remains a disorder with no simple "pill" for a cure, a number of treatment methods can considerably improve patients' condition. The most effective are early intensive behavioral interventions, which in many cases lead to meaningful progress in language, intellect, and social interaction. Medication therapy complements these interventions, helping to control symptoms that interfere with learning (aggression, hyperactivity, anxiety), and its benefit has been demonstrated, especially for atypical antipsychotics in severe behavior. Documented cases of successful treatment, in particular the phenomenon of "optimal outcome", when a child loses the ASD diagnosis after years of therapy, show that early intervention can change a patient's life trajectory. At the same time, most people with autism continue to need support, and the task of medicine is to maximize their quality of life and independence.

Outlook. Modern research is opening new horizons in autism treatment:

• Gene therapy and molecular drugs. Deciphering the genetic causes of ASD makes it possible to develop targeted interventions. In the coming years, specific treatments for subgroups may be introduced, for example gene therapy for Angelman syndrome and new drugs for syndromes with SHANK3 or neuroligin mutations. This is a step toward personalized medicine, in which therapy will be selected individually based on the patient's biomarkers.
• Stem cells and regenerative medicine. Clinical trials of cell therapy in autism are ongoing; future studies with larger samples are expected to answer whether cognitive function can be reliably improved with MSCs. Standardized products (for example, stem cell exosomes) may be developed to address neuroinflammation in ASD.
• Neuromodulation. Technologies for noninvasive influence on the brain are being refined. Repetitive transcranial magnetic stimulation is already being studied as a tool for improving neuroplasticity; in the future, TMS protocols for speech development or for reducing social anxiety may appear. Transcranial direct current stimulation (tDCS) combined with learning sessions is also promising.
• Digital technologies and artificial intelligence. Computer programs and apps for children with autism are increasingly used, from interactive social learning games to systems that help teach emotion recognition. In the future, AI may personalize learning plans, track progress by analyzing videos of sessions, and suggest optimal strategies to therapists (based on big data from successful cases).
• Nobel horizons. Fundamental discoveries recognized with Nobel Prizes, such as the mechanisms of synaptic transmission, cell reprogramming, and gene editing, are already laying the groundwork for new treatment methods. We can hope that the further combination of neurology, genetics, and immunology will lead to fundamentally new therapies that can influence the very biological nature of autism rather than merely compensate for its manifestations.

In summary, autism treatment is a multilevel and long-term process that requires teamwork among doctors, therapists, and the family. Evidence-based medicine currently offers clear strategic directions: early intensive education, targeted medication support, and individualized approaches. Implementing such a comprehensive protocol at CSM Clinic aims to give every child with ASD the opportunity to reach their potential as fully as possible. The prospects opened by modern research give grounds for cautious optimism: as science advances, the notion of "curing autism" may take on a new meaning, as reaching a state in which a person with ASD can live happily and productively, overcoming the challenges of the disorder with the help of science and public support.

Device-Based Treatments for Autism: Effectiveness and Implementation

Besides behavioral therapy and medication, researchers are studying device-based methods for autism spectrum disorder (ASD) – non-drug interventions that use special equipment. These include hyperbaric oxygen therapy (HBOT), neurobiofeedback (EEG neurofeedback), transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS) and other technologies (for example, vagus nerve stimulation or photobiomodulation). Below is an overview of the evidence for each method, the latest clinical studies and protocols, and the prospects for introducing these technologies in different countries.

Hyperbaric Oxygen Therapy (HBOT)

How it works: HBOT involves breathing oxygen under increased pressure in a hyperbaric chamber, which causes tissue hyperoxia. In theory, this may improve cerebral perfusion, reduce inflammation and oxidative stress, and thereby ease autism symptoms. Children with ASD have often shown signs of cerebral hypoperfusion and neuroinflammation, so HBOT has been considered a way to influence these pathophysiological processes.

Effectiveness: Early studies of HBOT in autism produced mixed results. Small trials reported improvements in social interaction, speech and cognitive awareness in some children. For example, in a 2009 placebo-controlled study, 40 HBOT sessions (1.3 ATA, 24% O₂) led to statistically significant improvements in speech, social interaction and overall functioning as rated by clinicians, compared with sham treatment. At the same time, a 2007 review by the Canadian agency AETMIS found insufficient evidence that HBOT is effective in autism and classified the method as experimental.

Recent clinical studies: More recent work gives cautiously optimistic data. A 2025 meta-analysis that pooled 17 studies (890 patients) showed a moderate positive effect of HBOT: a reduction in core autism symptoms (standardized mean effect of about –0.66) and improvement in some domains – communication, cognitive awareness and behavior. However, the authors emphasize that the quality of the included studies was low, with high heterogeneity, so confidence in these results is limited. In a 2023 randomized controlled trial (Egypt, n=180), three groups were compared: HBOT (40 sessions over 2 months), risperidone (standard drug therapy for 6 months) and placebo. After a year of follow-up, all groups showed lower CARS and ATEC scores, but the most pronounced improvement was in the HBOT group (risperidone came next, and the smallest changes were in the placebo group). The study concluded that both HBOT and risperidone reduce core autism symptoms, but HBOT showed a better result than drug therapy. There are also data on combining HBOT with other therapies: in a 2021 study, combining hyperbaric chamber sessions with the Tomatis auditory stimulation method produced more pronounced progress in symptoms than either method alone. A separate 2024 retrospective analysis indicates that children who received ABA therapy together with HBOT (≥40 sessions at 2.0 ATA, 60 minutes each) acquired more language skills over a year than those who received ABA alone.

Clinical protocols and reported cases: There is no standardized HBOT protocol for autism yet, but studies most often use a pressure of 1.3–1.5 ATA and 100% oxygen for 60 minutes, in a course of about 40 sessions (5–7 sessions per week). Parents of children with ASD reported improved concentration and speech and less irritability after such courses. In 75–90% of subjective parent reports, some positive change was noted after an HBOT course. The therapy is usually well tolerated: at a pressure of about 1.5 ATA, side effects are limited to ear discomfort or, in isolated cases, minor barotrauma. Researchers note that HBOT is a relatively safe procedure when the protocol is followed (for example, 1.3 ATA does not cause toxic effects).

Use in practice: Despite some encouraging results, HBOT is not yet part of the standard of care for autism. In the USA, this method is not FDA-approved for autism; leading professional organizations (the Undersea and Hyperbaric Medical Society and the European Committee for Hyperbaric Medicine) have not included autism among the indications for HBO therapy. Most insurance companies do not cover HBOT for ASD, considering it an experimental approach. Nevertheless, a number of private clinics around the world (the USA, Canada, Europe, the Middle East) offer paid HBOT programs to parents as an additional therapy. For example, in Egypt and China HBOT is being actively studied in clinical trials, and local doctors report successful cases within research protocols. In Ukraine and most other countries, HBOT for children with autism is used only occasionally, at the parents' initiative, and is not part of state programs. Further multicenter studies are needed to establish the effectiveness of HBOT and to develop standard indications and protocols.

Neurobiofeedback (EEG Neurofeedback Therapy)

How the method works: Neurofeedback is EEG-based biofeedback. During sessions, the child receives audio or visual signals about their own brain activity and learns to deliberately change certain EEG parameters. Children with ASD often show abnormal EEG activity (excess theta rhythm, reduced beta and mu rhythms). The goal of therapy is to normalize brain rhythms, which in theory should improve attention, self-regulation and behavior. A typical protocol is about 30–40 training sessions, in which a reduction of slow waves (4–8 Hz) and an increase in beta/mu activity (8–15 Hz) is encouraged. In some children, the improvements achieved during a neurofeedback course persisted 12 months after therapy.

Effectiveness and research: A number of studies since the late 2000s have reported positive changes with neurofeedback. In particular, improvements were noted in executive functions, verbal and nonverbal communication, sociability, imitation ability, and reductions in stereotyped behavior and hyperactivity after a course of 40 sessions. A 2020 systematic review (20 studies, 443 children) found that 94% of studies (including uncontrolled ones) recorded positive results of neurofeedback therapy. Moreover, even among the few available randomized controlled trials, most showed significant improvement in autism symptoms in the neurofeedback groups compared with the control group. The reported effects include improved attention, reduced impulsivity and anxiety, and increased social interaction. In one fMRI study, clinical improvements were found to correlate with changes in brain activation in areas associated with imitation and social cognition. Thus, the accumulated data suggest that neurofeedback may be an effective alternative therapy for ASD, including long-term positive effects after training is completed. At the same time, the authors of the review stress the need to standardize optimal protocols (the wave frequencies to train, the length of the course, and so on) and to conduct larger blinded studies to raise the level of evidence.

Clinical cases and protocols: Examples of the use of neurobiofeedback are described in many countries. For instance, Dutch researchers (Kouijzer et al.) showed back in 2009–2010 that after 40 sessions of EEG feedback, children with autism improved their performance on cognitive tests and showed less problem behavior; 12 months after treatment, the effect was partly maintained. A typical session lasts about 30 minutes: the child does computer exercises or plays a "game" and receives reinforcement when their brain waves change in the desired direction. For example, in the SMR-beta training protocol, a reduction in theta (4–7 Hz) and an increase in beta activity (12–15 Hz) is associated with better concentration and fewer stereotyped behaviors. In clinical settings, 2–3 sessions per week are usually held over several months. The method is considered very safe, since it is non-invasive training; side effects are hardly ever noted, apart from possible fatigue or a short-lived headache after a session in some children.

Use in different countries: Neurofeedback for children with ASD is offered by numerous private centers and therapy clinics in the USA, Europe (in particular, the Netherlands and Germany) and other countries. This method is not yet included in official clinical guidelines for autism treatment, but it has gained popularity as a supplement to the main therapies. In the USA, neurofeedback is considered an unconventional but permitted procedure – EEG devices with training software are available on the market, and their use is only loosely regulated. In EU countries, there are neurotherapy centers that use this approach, but state health systems rarely cover such services. In Ukraine, neurofeedback is also offered in several private centers as a method of correcting behavior and attention in children (mostly for ADHD, but sometimes for ASD). Future prospects depend on building up the evidence base: if new large RCTs confirm its effectiveness, neurofeedback may be integrated into standards of care as a safe, non-invasive approach to correcting neuronal dysfunction in autism.

Transcranial Direct Current Stimulation (tDCS)

How the method works: tDCS delivers a weak direct electric current (usually 1–2 mA) through the brain between two electrodes placed on the scalp. The current does not directly cause neurons to fire, but it modulates neuronal excitability: the anode increases and the cathode decreases the excitability of the cortex under the electrode. In ASD, tDCS targets brain areas responsible for social interaction and behavior – most often the prefrontal cortex or the temporoparietal regions – with the aim of improving behavioral regulation and speech or reducing irritability. Procedures are done daily or every other day, a session lasts about 20 minutes, and a course is 10 to 20 sessions.

Effectiveness and research: Over the past decade, several pilot RCTs of tDCS in autism have been carried out, although the samples are still small. A 2022 systematic review analyzed 11 RCTs of tDCS in children and adolescents with ASD. Notably, all of the studies recorded improvement in at least one of the measured outcomes in the tDCS group. The most frequently reported results were a reduction in behavioral problems and irritability and improved attention and verbal communication. In particular, anodal stimulation of the prefrontal cortex was associated with fewer manifestations of autistic behavior (for example, better social responses and fewer stereotyped movements). On average, 88% of studies with multi-session tDCS (≥10 sessions) showed statistically significant progress on at least one measure compared with control conditions. No serious adverse events were found: across 35 studies in total (745 children, 6,587 sessions), no serious side effects were recorded. Children only occasionally complain of mild skin tingling, itching under the electrodes or a slight headache – all of which are transient. The review therefore concludes that tDCS is a safe and partially effective method for children with neurodevelopmental disorders (including ASD), but larger double-blind RCTs are needed to assess the clinical significance of the effects.

More recent studies are exploring different tDCS parameters. For example, one project (2018) tested bilateral frontal stimulation in adolescents with autism and found improved emotional regulation; another study tested a simulated protocol (sham) against the real one – and although the difference was small, a trend toward improved social interaction was seen in the tDCS group. A problem with many studies is small samples and the lack of blinded control. New RCTs are currently under way (for example, in the USA and Europe) to determine the optimal stimulation sites (DLPFC, temporal cortex and so on), current strength and course length for the maximum effect with minimal side effects.

Clinical protocols and use: In all studies of tDCS in autism, the procedure is supervised by medical staff; parents cannot carry out stimulation on their own without supervision. There are no standard protocols yet, but a common regimen is: anode over the left dorsolateral prefrontal cortex (an area associated with the control of emotions and behavior), with the cathode over the opposite forehead or the squamous part of the temporal bone. A session lasts 20 minutes at a current of 1 mA, for 10–15 days in a row. As a result, some children show fewer repetitive movements, better eye contact and calmer behavior. One reported case: a 6-year-old child with autism in Italy showed progress in speech and play after 10 tDCS sessions – this is described as an individual clinical success case. However, other children may not respond as noticeably – there are probably individual differences in the response to neurostimulation.

Status of implementation: tDCS is still an experimental method for autism. From a regulatory standpoint, it is not approved in the USA or the EU for use in children with ASD, but its use within research is permitted. In some European countries (e.g., Italy and Spain) and in Australia, individual clinics offer tDCS to children with neurodevelopmental disorders on an individual (off-label) basis, but this is an isolated practice. In the USA there are home tDCS devices, but their use in pediatrics is limited because of legal and ethical issues. Overall, tDCS has not yet become a routine procedure for treating autism in any country – its future depends on the results of ongoing research. If larger trials confirm its effectiveness (even moderate) in easing ASD symptoms, the method may be adopted more widely, since it is inexpensive, non-invasive and simple to use. An area of active development is the personalization of tDCS: in particular, combining it with neuroimaging (fMRI, EEG) to target specific brain networks that are dysfunctional in autism.

Transcranial Magnetic Stimulation (TMS)

Description of the method: TMS is non-invasive brain stimulation with magnetic fields. A coil placed on the head generates brief magnetic pulses that induce electric currents in the cerebral cortex. Unlike tDCS, TMS makes neurons respond directly (generate action potentials), so the effect is more localized and depends on the stimulation frequency. Low-frequency TMS (≤1 Hz) usually suppresses cortical excitability, while high-frequency TMS (5–20 Hz) enhances it. In autism, both approaches have been studied: low-frequency rTMS over the prefrontal cortex to reduce irritability and repetitive behavior, and high-frequency rTMS over the temporoparietal regions to improve social cognition and speech. A course of rTMS usually consists of about 10–20 sessions (daily or every other day), 20–30 minutes each.

Effectiveness and evidence: Over the past 15 years, more than a dozen clinical trials of TMS in children and young people with autism have been conducted. A 2023 review (16 studies, including 9 controlled) noted that most studies report improvement in both cognitive and behavioral symptoms after a course of TMS. A meta-analysis of 12 studies showed a moderate effect: with low-frequency rTMS applied to the dorsolateral prefrontal cortex, executive functions improved and the severity of Criterion B symptoms (restricted and stereotyped patterns of behavior) decreased significantly. In particular, the pooled effect size was Hedges' g = 0.735 for cognitive measures (that is, a moderate-to-large positive effect) and g = 0.435 for behavioral symptoms. These changes are statistically significant (p < 0.01 for cognitive and p < 0.001 for behavioral outcomes), which points to a real therapeutic potential of TMS in autism. Some controlled studies also noted a reduction in irritability and hyperactivity symptoms (on the ABC scale) after 1 Hz rTMS over the prefrontal cortex in adolescents with ASD. There are data on improved eye-to-eye contact and social attention after stimulation of the dorsoventral prefrontal cortex (responsible for social perception). It is important that most of these studies are small, and only one was a double-blind, placebo-controlled RCT. Studies often used a waitlist design or a before/after comparison without a true sham, which lowers the level of evidence.

Safety: TMS is considered a relatively safe method, and in the context of autism this has been confirmed by a dedicated analysis. A 2022 meta-analysis assessed the frequency of side effects in 11 studies of TMS in ASD: the overall prevalence of adverse events was about 25%, and all of them were mild and transient. The most common were headache after the session (about 10% of cases), short-term facial muscle discomfort (15%), and increased excitability or irritability that day (up to 21%). Other possible effects were mild dizziness (8%) and pain at the stimulation site on the scalp (6%). No serious complications (such as seizures or fainting) were reported; the risk of an epileptic seizure when standard protocols are followed is considered extremely low. No autism-specific risk factors for adverse reactions were found either – their frequency did not depend on age, stimulation site or regimen (diagnostic vs. therapeutic TMS). Thus, the safety profile of TMS is favorable, which is important when considering the method for children.

Clinical use and protocols: Given its experimental status, there is currently no single TMS scheme for ASD. Studies most often used 1 Hz rTMS over the left dorsolateral prefrontal cortex (LDLPFC) – 15–20 minutes, 5 sessions per week for 2–4 weeks. This area is associated with executive functions and impulse control; the low frequency reduces cortical excitability and probably reduces repetitive behavior and aggression. Alternatively, a number of studies (including the group of Prof. M. Casanova) used high-frequency (10–18 Hz) TMS over the temporoparietal region (for example, the right posterior superior temporal gyrus, associated with social perception) in order to boost the activity of social neural networks. There are reports of cases in which, after a course of rTMS, parents noticed that the child became calmer, responded better when spoken to, and began using new words. For example, in one open-label study, 75% of children with high-functioning autism showed improvement on the Social Responsiveness Scale (SRS) after 2 weeks of TMS therapy. It is important to note that the effect of TMS often depends on the child's baseline characteristics: some of the greatest improvements were seen in older children or those with a lower baseline severity of autism. This suggests that in the future it will be necessary to identify who responds best to this method.

Status of implementation: The clinical use of TMS in autism is currently limited to research centers. From a regulatory standpoint, no country has approved TMS as a treatment for ASD. In the USA, TMS is officially approved for depression, obsessive-compulsive disorder and migraine, but its use in ASD is off-label and takes place only within clinical trials or on an individual basis. Some private facilities (such as TMS centers in Arizona and California) advertise so-called MeRT therapy for autism – a modified TMS with the frequency tuned according to EEG – but there is not yet enough scientific evidence for its benefits. In Europe, this method is also at the research stage: clinical trials of iTBS (intermittent theta burst stimulation) to improve social skills in autism are being conducted in France, Israel and Italy. Overall, TMS is not integrated into standard practice for ASD worldwide, but interest in it is growing. Prospects for development include the use of precise neuronavigation (to stimulate specific brain areas identified individually by MRI/EEG), the study of new protocols (for example, theta-burst stimulation, which can produce in a few minutes an effect equivalent to a longer rTMS course), and larger double-blind studies. Only after that can TMS be expected to be included in guidelines – if its effectiveness is reproduced at a high level of evidence.

Other Technologies (taVNS, Photobiomodulation and More)

Besides the methods described above, other device-based technologies are being tested to help people with autism:

• Transcutaneous auricular vagus nerve stimulation (taVNS): a non-invasive method of influencing the vagus nerve through electrodes attached to the outer ear (in the area innervated by the vagus nerve). Vagus nerve stimulation is known for its calming, anxiolytic effect and its ability to modulate neural networks associated with emotions and social interaction. A recent pilot project (USA, 2023) demonstrated that home taVNS sessions under remote supervision are feasible and safe for children with ASD. Twelve participants (aged 7–16) received 1 hour of ear stimulation daily for 2 weeks; 88.5% of sessions were completed, and side effects were minimal (most often a mild headache or tingling in the ear). Preliminary results pointed to reduced anxiety and improved sleep according to parents' reports after the taVNS course. Although this was an open-label study without a control group, it gives grounds for continuing to test the method in a larger sample. Other studies have also reported that taVNS may improve social cognition in autistic individuals. Importantly, the technology is compact and relatively inexpensive; the prospect is the development of personal devices for daily use at home under a doctor's supervision. RCTs studying taVNS in autism are currently under way – in particular, in China a double-blind study is planned of the effect of a 2-week stimulation course on behavioral and neuroimaging measures in children with high-functioning autism.
• Transcranial photobiomodulation (tPBM): this is light treatment – irradiating the scalp with red or near-infrared light to influence subcortical neurons. Light of a certain wavelength penetrates to a depth of several centimeters and may improve neuronal metabolism, reduce neuroinflammation and stimulate neuroplasticity. For autism the method is still new, but there are already encouraging results. In 2024, a randomized placebo-controlled study of tPBM in children aged 2–6 years with ASD was published. The active group received regular near-infrared irradiation of areas of the head, while the control group received sham procedures. Over 8 weeks of treatment, the CARS score decreased significantly more in the group receiving real photobiomodulation (a difference in change of about 7.23 points, p = 0.011). This indicates a noticeable reduction in autism severity on a clinical scale as a result of light therapy. In addition, EEG showed trends toward normalization of rhythms (reduced excess delta activity and increased theta activity) in children who received tPBM. No moderate or severe side effects were observed. The researchers' conclusion: tPBM is a safe and potentially effective method for addressing ASD symptoms that is worth studying further. This direction opens up interesting possibilities, since light therapy is non-invasive and can even be delivered with portable devices (such as a "light helmet"). Some commercial prototypes of such devices already exist.
• Other device-based methods: In isolated cases, deep brain stimulation (DBS) – the surgical implantation of electrodes in certain brain structures (for example, the basal ganglia or thalamus) – has been tried in adults with severe forms of ASD and aggression. However, the data are insufficient; this is a last-resort measure and a highly experimental path. Various types of sensory stimulation are also being studied: audiovisual training, interactive robotic systems and virtual reality for practicing social skills – but these approaches belong more to behavioral interventions with technical support than to biomedical treatments.

The main device-based methods, their effectiveness and the state of the evidence are summarized below:

Conclusions and Outlook

Overall review of effectiveness: Device-based treatments for ASD generally show moderate effectiveness in easing individual symptoms. None of the approaches reviewed is a "cure-all" or a stand-alone treatment, but each can target certain aspects of the difficulties seen in autism. HBOT potentially affects biological mechanisms (blood circulation, inflammation, metabolism) and has led to behavioral improvements in a number of studies, but it needs further confirmation with high-quality evidence. Neurofeedback therapy already has a relatively large amount of positive data on developing attention, communication and self-control in children – it stands out as safe and promising for long-term rehabilitation. Brain neuromodulation methods – tDCS and TMS – have so far shown modest but real benefits (for example, reduced stereotyped behaviors and irritability) and have proved safe in the pediatric population. Innovative technologies (such as vagus nerve stimulation or photobiomodulation) open up new directions, combining simplicity with targeted influence on the nervous system, but are still at the stage of testing hypotheses.

Level of evidence and latest research: All the methods reviewed need further randomized controlled trials to raise the level of evidence. Existing meta-analyses and systematic reviews give encouraging signals (e.g., significant effects of HBOT, neurofeedback and TMS), but they often note low study quality and small samples. It is important to conduct studies with a double-blind design (especially for TMS, neurofeedback and HBOT, to rule out the placebo effect), to enroll enough participants and to assess long-term effects. The latest clinical trials now under way (2023–2025) in different countries aim to refine the protocols: for example, to determine the optimal pressure and course length for HBOT, the electrode placement sites and parameters for tDCS/TMS, the number of sessions and target rhythms for neurofeedback, and so on. Researchers are also increasingly including objective endpoints – neuroimaging and neurophysiological measures (functional MRI, EEG, inflammation biomarkers) – to understand how these methods affect the brain and which mechanisms they change.

Use in practice: As of 2025, none of the device-based methods has been included in the standards of medical care for autism in the leading international protocols (NAP, NICE and others). Their use is very uneven: it depends more on the initiative of individual clinics or parents' requests than on state programs. In countries such as the USA and Canada, there is an active private sector offering neurofeedback, HBOT or even off-label TMS to children with autism, but these services are not covered by insurance and are not governed by uniform standards. In Europe (the Netherlands, Germany, the United Kingdom and others), device-based methods are used mainly within research or in rehabilitation centers; national health systems are still cautious about adopting them because of the lack of unambiguous evidence. China, India and the Middle East are regions where the number of publications on neuromodulation in ASD has grown in recent years, which may indicate more experimental practice and potential interest in introducing new technologies into treatment. For example, Chinese researchers have carried out a series of TMS and tDCS trials and published positive safety reviews, and several clinics in Israel and the UAE offer HBOT to children with autism. Ukraine is not on the sidelines either: some private rehabilitation centers are introducing neurofeedback and sensory technologies, but there are no recommendations at the national level. Overall, device-based methods are currently regarded as supplementary or alternative interventions at the discretion of the specialist and the family, when traditional approaches do not give a sufficient effect.

Prospects for development: The future of device-based technologies in autism therapy depends on the results of high-quality research and on the improvement of the technologies themselves. There are several key directions of development:

• Personalization and targeting: Moving away from the "one method for everyone" principle toward selecting therapy for a specific patient profile. For example, preliminary EEG/fMRI diagnostics could be used to determine who would benefit more from neurofeedback (in the case of pronounced rhythm abnormalities) and who from TMS of a particular area (in the case of dysfunction of specific networks). Neuronavigation algorithms for TMS are already being tested, which will allow more precise stimulation of the required brain areas and reduce the variability of results. A personalized approach may increase effectiveness and reduce unnecessary interventions.

• Combined use: There is a hypothesis that combining device-based methods with traditional ones will produce synergy. For example, HBOT + behavioral therapy has already shown better speech development than behavioral therapy alone. In the future, protocols are possible in which an intensive social-communication training program follows a course of neurofeedback (improved attention), or cognitive behavioral therapy follows TMS (reduced stereotyped behaviors) to consolidate skills. Such multimodal strategies could make the most of the window of neuroplasticity opened by device-based stimulation.

• Accessibility and miniaturization: Technological progress is moving toward portable devices for home use. Compact tDCS devices already exist, and there are projects for portable TMS (for example, helmets with coils) and for home neurofeedback systems via a tablet. If clinical trials confirm their safety and effectiveness, such devices could receive regulatory approval for use under periodic remote supervision by a doctor. This would significantly expand access to therapy, especially for families who cannot often visit specialized centers. One example is the successful experience with remotely guided taVNS at home, which can serve as a model for other methods.

• Understanding the mechanisms: Alongside clinical data, it is important to understand why and how these methods work. Studies in animal models of ASD (for example, a mouse model with valproic acid exposure) show that HBOT may reduce neuroinflammation and influence gene expression (in particular, GRIN2B) in the brain. Uncovering such neurobiological mechanisms will help optimize protocols (for example, tune the TMS frequency that stimulates neuroplasticity, or select the light wavelength for maximum effect). Once the mechanisms are understood, it will be easier to persuade both the medical community and regulators that the use of these methods is justified.

In conclusion, it should be emphasized that device-based methods are a promising addition to the range of autism therapies, but for now they do not replace traditional evidence-based approaches (behavioral interventions, educational support and medication when needed). Their introduction into clinical practice in different countries is proceeding gradually and cautiously. Wide recognition will require further high-quality evidence – only then will international clinical guidelines be able to recommend these technologies. At the same time, some families and specialists, having weighed the risks and potential benefits, already use HBOT, neurofeedback, TMS or other methods as part of a comprehensive plan. As science and technology develop, we are likely to see new evidence-based protocols for device-based therapy that may take a worthy place in comprehensive care for people with ASD.

Author: O. S. Kiian
Founder and Director of CSM Clinic