Evidence-based interventions for attention-deficit/hyperactivity disorder

EBI-ADHD: Evidence-Based Interventions for ADHD

Attention-Deficit/Hyperactivity Disorder (ADHD)

Attention-Deficit/Hyperactivity Disorder

Acupuncture is a Traditional Chinese Medicine practice that involves inserting fine needles into specific points on the body to regulate energy flow (Qi) and restore physiological balance. In the context of neurodevelopmental disorders, it is utilized as a complementary therapy believed to modulate neurotransmitters (such as glutamate and GABA) and trigger neurological responses to alleviate symptoms. Treatment protocols are typically customized to the individual by qualified practitioners.

Alpha-2 agonists, specifically clonidine and guanfacine, are FDA-approved ADHD treatments that target brain receptors to regulate norepinephrine and attention. While both medications can be safe and effective in treating ADHD, they may require close monitoring due to potential side effects (e.g., clonidine can lower blood pressure and cause low heart rate and sedation). 

Due to their similarities, they are grouped together for this study.

Amphetamines, specifically dexamfetamine and lisdexamfetamine (sold under names such as), are FDA-approved stimulant treatments that increase dopamine and norepinephrine levels to regulate attention and impulsivity. While effective, they are controlled substances that require close monitoring due to abuse potential and side effects (e.g., appetite suppression, increased blood pressure, and sleep disruption).

Due to their pharmacological similarities, all formulations of amphetamines are grouped together for this study.

Atomoxetine is an FDA-approved non-stimulant medication (in children >6 years of age and above) that functions as a selective norepinephrine reuptake inhibitor to regulate attention and impulsivity. Unlike stimulants, its therapeutic effects may take several weeks to emerge, and it requires monitoring due to potential side effects such as nausea, appetite loss and insomnia.

Bupropion is a medication primarily FDA-approved for depression and smoking cessation, though it is used off-label for ADHD. It functions by inhibiting the reuptake of dopamine and norepinephrine to potentially improve attention and focus. While generally considered safe, it requires monitoring for side effects such as insomnia, dry mouth, and an increased risk of seizures.

L-carnitine is a naturally occurring amino acid derivative that plays a crucial role in energy production. It is synthesized in the body from the amino acids lysine and methionine and is also obtained from dietary sources, particularly meat and dairy products. L-carnitine is essential for the transport of long-chain fatty acids into the mitochondria, where they are oxidized to produce energy. 

Beyond its primary function in fatty acid metabolism, recent research has highlighted L-carnitine involvement in various physiological processes, including cellular energy balance, neuroprotection, and muscle function. These functions make L-carnitine a critical component in overall metabolic health and physical performance.

Given its role in energy metabolism and cellular health, L-carnitine has been investigated for its potential benefits in various health conditions, including cardiovascular diseases, muscle disorders, and neurodegenerative diseases. It is also explored for its possible therapeutic effects in Autism Spectrum Disorder (ASD).

Centanafadine is an investigational medication (not yet FDA-approved) being studied for adult ADHD that functions as a triple reuptake inhibitor of norepinephrine, dopamine, and serotonin. While clinical trials have shown promise, it requires monitoring for side effects such as decreased appetite, headache, and nausea.

Cognitive Behavioral Therapy is a psychotherapeutic intervention that addresses maladaptive patterns of thinking and behavior. By teaching individuals to recognize cognitive distortions, face fears, and develop practical problem-solving skills, it aims to reduce emotional distress and improve daily functioning.

Cognitive training involves structured, repetitive mental exercises (often delivered via computer-based platforms) designed to enhance executive functions like attention, working memory, and problem-solving. Used as a complementary intervention for ADHD and autism, it aims to improve focus and adaptive skills, typically functioning as part of a broader, personalized treatment plan.

In recent years, a promising way has been to combine the computer practice with metacognitive training or social skill groups to favor the transfer in daily life.

Dasotraline is an investigational medication (development halted in 2020) that functions as a dopamine and norepinephrine reuptake inhibitor without triggering dopamine release. While it showed promise in pediatric trials for regulating ADHD symptoms, it was not FDA-approved due to inconsistent results in adults and side effects such as insomnia, anxiety, and decreased appetite.

Desipramine is a tricyclic antidepressant that inhibits norepinephrine reuptake and is sometimes used off-label to treat ADHD. While FDA-approved for depression, its use in ADHD has declined due to the availability of safer options and the need to monitor for side effects such as cardiac conduction changes, dry mouth, and sedation.

Dialectical Behavioural Therapy (DBT) is a psychotherapeutic framework originally developed for borderline personality disorder that focuses on improving emotional regulation, distress tolerance, and mindfulness. It is increasingly adapted for other conditions, including neurodevelopmental disorders, to help individuals develop skills for awareness, acceptance, and managing difficult emotions.

Specific Dietary Programmes utilize nutritional interventions to target biological processes like inflammation or metabolic function. These interventions typically involve the strict elimination of potential allergens (e.g., wheat, dairy) or additives to alleviate somatic issues and potentially improve behavioral symptoms.

Homeopathy is an alternative medicinal system based on the principle of treating ailments with highly diluted substances. There are currently no FDA-approved homeopathic products, and while benefits are often attributed to the placebo response, treatments require caution as they may still contain active ingredients or lead to adverse effects.

Methylphenidate is an FDA-approved stimulant medication widely used as a first-line treatment for ADHD. It functions by inhibiting the reuptake of dopamine and norepinephrine to regulate inattention and impulsivity. Like other stimulants, it is a controlled substance requiring close monitoring due to abuse potential and side effects (e.g., appetite suppression, and sleep disruption).

Mindfulness is a therapeutic technique that involves the self-regulation of attention to focus on the present moment with an attitude of openness and acceptance. Often derived from Buddhist traditions and adapted for clinical use, it aims to improve emotional regulation and affect tolerance, distinct from physical mindfulness activities like yoga.

Modafinil is a wake-promoting medication primarily FDA-approved for sleep disorders (e.g., narcolepsy), though it is sometimes used off-label for ADHD. It functions by blocking dopamine reuptake to increase alertness and focus. Usage requires medical monitoring due to potential side effects such as headaches, insomnia, and palpitations.

Multimodal Behavioral Training integrates multiple therapeutic components - specifically parent training, classroom management, and child-focused skills training—to address symptoms across diverse settings. By coordinating support between home, school, and social environments, this approach aims to ensure consistent behavioral reinforcement and facilitate the generalization of skills.

Neurofeedback is a non-pharmacological intervention that uses real-time monitoring to teach individuals how to self-regulate their brain activity. By providing immediate visual or auditory feedback on brain wave patterns, it aims to improve attention and behavioral control, though clinical evidence regarding its efficacy remains mixed and requires further investigation.

Organizational Skills Interventions are behavioral strategies designed to address difficulties with time management, planning, and material organization often found in ADHD. By using techniques like prompting and positive reinforcement to facilitate task completion, these interventions serve as either stand-alone or adjunct treatments to help individuals manage daily activities and schoolwork.

Parent-Mediated Interventions (PMI) involve training parents to function as the primary agents of therapeutic change. By applying techniques in the daily environment, these interventions aim to facilitate early intervention and improve skill generalization. While the delivery model is consistent, the focus adapts to the condition: interventions for Autism typically target social communication and joint attention, whereas those for ADHD primarily focus on behavior management and structural support.

Physical Training (encompassing interventions such as) involves structured or unstructured bodily movement to enhance physical and mental well-being. It is utilized as a complementary therapy to improve motor coordination, emotional regulation, and social interaction through individual or group-based activities.

Polyunsaturated Fatty Acids (PUFAs), specifically Omega-3s like EPA and DHA, are essential fatty acids critical for brain function and development. Because the human body cannot synthesize them, they must be obtained through diet or supplementation, where they are utilized as a complementary intervention to support cognitive health and reduce inflammation.

Probiotics are living microorganisms consumed to maintain intestinal microbial balance. Through the gut-brain axis, they are hypothesized to influence neurological and psychological conditions by modulating the immune system and neurotransmitter production.

Social Skills Training (SST) is a non-pharmacological intervention designed to improve interpersonal functioning in individuals with ADHD who face social challenges. Through group activities and structured, it teaches emotional regulation, communication skills, and the interpretation of verbal and non-verbal cues.

Transcranial Direct Current Stimulation is a non-invasive brain stimulation technique that delivers low-intensity electrical currents to the scalp. It aims to modulate neuronal excitability (specifically in the dorsolateral prefrontal cortex) to potentially improve social communication, cognitive flexibility, and reduce repetitive behaviors.

Repetitive Transcranial Magnetic Stimulation is a non-invasive neuromodulation technique that uses electromagnetic fields to stimulate or inhibit specific brain regions. Typically administered in daily outpatient sessions, it is studied for its ability to alter neuronal activity patterns associated with psychiatric and neurodevelopmental conditions.

Viloxazine is an FDA-approved non-stimulant medication for the treatment of ADHD in children and adults. Notably, most clinical trials demonstrating its efficacy have emerged from a single research team (the manufacturer's development program). It functions primarily by inhibiting the reuptake of norepinephrine and modulating serotonin activity to improve symptoms. Originally developed as an antidepressant, this formulation requires clinical monitoring for potential side effects.

Vitamin D is an essential nutrient critical for bone health, immune regulation, and neuroprotection. Research explores its role in modulating genes and neuronal pathways involved in social behavior and cognition, particularly in individuals with documented deficiencies.

Zinc is an essential trace mineral that supports immune function and enzyme activity. It is investigated as a complementary intervention for ADHD due to its role in regulating dopamine, a neurotransmitter implicated in the disorder. While naturally available in food, supplementation is explored to address potential deficiencies that may impact behavior and cognition, though dosage requires monitoring to remain within safe limits.

Legend

Intervention effect compared to placebo or other controls

Evidence Quality (how confident we are in the finding)