Comparative analysis of electroencephalogram (EEG) data gathered from the frontal region with other brain regions affected by attention deficit hyperactivity disorder (ADHD) through multiresolution analysis and machine learning techniques.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by repeated patterns of hyperactivity, impulsivity, and inattention that limit daily functioning and development. Electroencephalography (EEG) anomalies correspond to changes in brain connection and activity. The authors propose utilizing empirical mode decomposition (EMD) and discrete wavelet transform (DWT) for feature extraction and machine learning (ML) algorithms to categorize ADHD and control subjects. For this study, the authors considered freely accessible ADHD data obtained from the IEEE data site. Studies have demonstrated a range of EEG anomalies in ADHD patients, such as variations in power spectra, coherence patterns, and event-related potentials (ERPs). Some of the studies claimed that the brain's prefrontal cortex and frontal regions collaborate in intricate networks, and disorders in either of them exacerbate the symptoms of ADHD. , Based on the research that claimed the brain's prefrontal cortex and frontal regions collaborate in intricate networks, and disorders in either of them exacerbate the symptoms of ADHD, the proposed study examines the optimal position of EEG electrode for identifying ADHD and in addition to monitoring accuracy on frontal/ prefrontal and other regions of brain our study also investigates the position groupings that have the highest effect on accurateness in identification of ADHD. The results demonstrate that the dataset classified with AdaBoost provided values for accuracy, precision, specificity, sensitivity, and F1-score as 1.00, 0.70, 0.70, 0.75, and 0.71, respectively, whereas using random forest (RF) it is 0.98, 0.64, 0.60, 0.81, and 0.71, respectively, in detecting ADHD. After detailed analysis, it is observed that the most accurate results included all electrodes. The authors believe the processes can detect various neurodevelopmental problems in children utilizing EEG signals.

Examination of Excessive Mind-Wandering Following Attention-Deficit and Hyperactivity Disorder Treatment in Adults.

Although mind-wandering (MW) is a part of attention deficit and hyperactivity disorder (ADHD), the impact of psychostimulants on excessive MW remains unclear. We aimed to elucidate how psychostimulants impact the MW of adult ADHD patients post treatment. This cross-sectional cohort study consisted of 54 randomly selected ADHD patients who applied to our psychiatry outpatient clinic and 40 healthy controls. The ADHD patients were administered methylphenidate or atomoxetine. A Semi-Structured Sociodemographic and Clinical Data Form, the Adult ADHD Self-Report Scale (ASRS), and the Mind Excessively Wandering Scale (MEWS) were applied. Routine psychiatric assessments in the 1st, 2nd, and 3rd months of pharmacological treatment were carried out by a psychiatrist. The pre-treatment MEWS score of the ADHD patients was 26.09 ± 1.92, which significantly decreased to 12.78 ± 2.54 post-treatment (F = 715.250, p < .001). A statistically significant difference was identified between the mean pre-treatment ASRS total score (44.07 ± 10.09) and post-treatment score (27.34 ± 11.22; F = 50.364, p < .001). A lifetime history of alcohol/substance use was positively associated with the MEWS score. ADHD pharmacotherapy led to significant reductions in MW. Recognizing the interaction between MW and ADHD could help in the design of more specific and comprehensive interventions.

Corrigendum: Neurocognitive and cerebellar function in ADHD, autism and spinocerebellar ataxia.

[This corrects the article DOI: 10.3389/fnsys.2023.1168666.].

Electronic Health Records for Research on Attention-Deficit/Hyperactivity Disorder Pharmacotherapy: A Comprehensive Review.

Objectives: Randomized controlled trials (RCTs) have shown that attention-deficit/hyperactivity disorder (ADHD) medications significantly reduce symptomatology at a group level, but individual response to ADHD medication is variable. Thus, developing prediction models to stratify treatment according to individual baseline clinicodemographic characteristics is crucial to support clinical practice. A potential valuable source of data to develop accurate prediction models is real-world clinical data extracted from electronic healthcare records (EHRs). Yet, systematic information regarding EHR data on ADHD is lacking. Methods: We conducted a comprehensive review of studies that included EHR reporting data regarding individuals with ADHD, with a specific focus on treatment-related data. Relevant studies were identified from PubMed, Ovid, and Web of Science databases up to February 24, 2024. Results: We identified 103 studies reporting EHR data for individuals with ADHD. Among these, 83 studies provided information on the type of prescribed medication. However, dosage, duration of treatment, and ADHD symptom ratings before and after treatment initiation were only reported by a minority of studies. Conclusion: This review supports the potential use of EHRs to develop treatment response prediction models but emphasizes the need for more comprehensive reporting of treatment-related data, such as changes in ADHD symptom ratings and other possible baseline clinical predictors of treatment response.

ADHD and cognitive disengagement syndrome symptoms related to self-injurious thoughts and behaviors in early adolescents.

The current study examined attention-deficit/hyperactivity disorder (ADHD) dimensions and cognitive disengagement syndrome (CDS) symptoms in relation to self-injurious thoughts and behaviors (SITBs) in an early adolescent sample. Participants were 341 adolescents ages 10-12 years (52.2% female; 37.8% people of color) recruited from the community. Caregivers reported on CDS and ADHD symptoms. Adolescents completed a rating scale and were administered an interview assessing SITBs. We estimated associations using logistic regression in a stepped fashion: (1) no adjustment, (2) adjustment for sex, race, family income, and psychotropic medication use, and (3) further adjustment for depressive symptoms. In this early adolescent community sample, 22.9% reported a history of suicidal ideation, 8.2% reported a history of a suicide plan, 6.2% reported a history of non-suicidal self-injury (NSSI), and 16.4% met a clinical cutoff for current suicide risk. Across most analyses using rating scale or interview methods, higher mean CDS scores were related to endorsement of suicidal ideation and planning. ADHD inattentive (IN) and hyperactive-impulsive (HI) symptoms were associated with endorsement of NSSI, and ADHD-IN symptoms were associated with thoughts of suicide and/or plan measured via questionnaire, though effects were less robust and not significant, potentially due to low base rates impacting statistical power. This study adds to a growing body of research highlighting the importance of screening for CDS symptoms among individuals with and without ADHD. More research, especially longitudinal work, is needed that examines possible differential pathways to SITBs by ADHD and CDS symptoms to advance SITB prevention, early detection, and intervention.

Effectiveness of virtual reality glasses versus white noise on dental anxiety in children with attention-deficit hyperactivity disorder: A randomised controlled clinical trial.

BACKGROUND: Management of children with attention-deficit hyperactivity disorder (ADHD) can be challenging due to their disruptive behaviour. Basic behaviour management techniques (BMTs) may not be sufficient, and adjunctive strategies such as virtual reality (VR) glasses or white noise can be employed. AIM: To assess and compare the effectiveness of VR, white noise and basic BMTs on dental anxiety and behaviour of children with ADHD. DESIGN: Forty-eight children with ADHD were recruited for this parallel, three-armed randomised controlled clinical trial, which involved three visits at one-week intervals, including examination, preventive measures and restorations. Children were randomly divided into three groups: VR, white noise and basic BMTs. Outcome measures were Faces Image Scale (FIS), Heart Rate (HR) and Venham's Behaviour Rating Scale (VBRS). RESULTS: No significant difference was found between the groups in FIS scores. White noise group had a significantly lower mean HR than control group in all visits. Scores of VBRS in VR and white noise groups were significantly lower than those in the control group during the restorative visit. CONCLUSIONS: VR and white noise could be beneficial in managing dental anxiety and improving behaviour in children with ADHD and could be used as adjunctive strategies to basic BMTs.

Sex differences in physiological correlates of affectively driven decision-making behavior in adult ADHD.

BACKGROUND: Sex differences in the symptomatology of adults with attention-deficit/hyperactivity disorder (ADHD) have often been overlooked when studying behavioral abnormalities. However, it is known that women exhibit considerably more stronger symptoms related to emotional competence than men. Since affective functions significantly influence the processing of risky decision-making and risk-engagement, we assume that risky behavior in ADHD is affected by sex differences. Therefore, we specifically investigated sex-specific effects on the interaction between emotionally induced changes in physiology and behavioral performance on a decision-making task. METHODS: Skin conductance responses of twenty-nine adults with ADHD (n = 16 male; n = 13 female) and thirty-three adults in the control group (n = 14 male; n = 19 female) were recorded during the performance in a modified version of the Balloon Analogue Risk Task (BART). Additional questionnaires were used to reveal insights in the self-assessment of emotional competence, risk perception, and feedback sensitivity. Emotional arousal and decision-making behavior were analyzed using linear mixed-effects models. RESULTS: Results showed different effects of sex on risk behaviors in controls and ADHD. In contrast to healthy controls, female adults with ADHD showed a significantly greater risk engagement in the BART compared to males with ADHD. This contrary sex relation was not observed in skin conductance responses and revealed a significantly different sex-dependent correlation of body response and behavioral task performance in ADHD. Comparisons with results from self-assessments furthermore indicate a reduced behavioral self-perception in women with ADHD, but not in men. CONCLUSION: In summary, we found an altered interaction between physiological activity and risky behavior in women with ADHD. Thus, the present study indicates a reduced sensitivity towards the own bodily responses in women with ADHD, which could consequently cause increased risky DM behavior in daily life. The current results suggest that more consideration needs to be given to sex-specific effects on physiological processes and behavior in adults with ADHD.

Abnormal Structure and Function of Parietal Lobe in Individuals With Attention Deficit Hyperactivity Disorder (ADHD): A Systematic Review Study.

Introduction: Abnormal brain structure and function have been reported in individuals with attention deficit hyperactivity disorder (ADHD). This study investigated the parietal lobe structure and function alteration in individuals with ADHD. Methods: In this systematic review, we searched English papers in accordance with the PRISMA (the preferred reporting items for systematic reviews and meta-analyses) approach. Studies were published between January 2010 and May 2021. Our search was conducted in two parts. Our first search was in July 2020, and our final search was in June 2021. A literature search identified 20 empirical experiments. Results: Functional magnetic resonance imaging (MRI) studies generally reported low activity and poor connectivity; structural MRI studies reported less gray matter in this lobe, and an echo study reported atrophy. In addition, electroencephalographic studies reported less connectivity of the parietal lobes in ADHD. Furthermore, the transcranial direct current stimulation intervention has shown that activation of this lobe improves attention and executive functions in children with ADHD. Finally, a deep transcranial magnetic stimulation study has demonstrated that activation of this lobe improves working memory. Conclusion: Functional and structural alteration of the parietal cortex has been reported in ADHD, which has a causal relationship with cognitive impairments. In sum, all included studies reported abnormal structure, function, or connectivity of the parietal lobe or improvement of cognitive functions with parietal lobe stimulation.

Case Report: Methylphenidate and venlafaxine improved abdominal nociplastic pain in an adult patient with attention deficit hyperactivity disorder, autism spectrum disorder, and comorbid major depression.

Introduction: Nociplastic pain (NP), classified as a third type of pain alongside nociceptive and neuropathic pain, is chronic pain arising from the amplification of nociceptive stimuli through central sensitization, despite the absence of tissue damage, sensory nerve damage, or disease. An important clinical feature of NP is that it is not only associated with pain but also with sensory hypersensitivity to sound and light and cognitive dysfunction, including mood and attention disorders. Recent studies have suggested that depression and developmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), coexist with NP at high frequency. Additionally, cognitive impairment in individuals with NP may be associated with these psychiatric comorbidities. However, to our knowledge, there are no reports on (1) multidimensional evaluation and diagnostic details of abdominal NP in adults with ADHD/ASD; (2) how ADHD drugs and antidepressants are administered when ADHD and depression coexist with NP; and (3) how central sensitization, brain function, and family relationship problems underlying NP are altered by treatments of ADHD and depression. Case presentation: Herein, we present the case of a 51-year-old woman with abdominal NP. She developed severe right lower abdominal pain and underwent a thorough medical examination; however, the physical, medical cause remained unknown, making treatment challenging. Additionally, she took time off work as she began to complain of insomnia and anxiety. She was referred to our pain center, where a diagnosis of depression, ADHD, and ASD was confirmed, and treatment with ADHD medication was initiated. While ADHD medications alone did not yield sufficient improvement, a combination of methylphenidate and the antidepressant venlafaxine eventually led to improvements in abdominal NP, depression, ADHD symptoms, central sensitization, and family relationship issues. During treatment, cerebral blood flow in the anterior cingulate, prefrontal, and parietal cortices also improved. Conclusion: The treatment of comorbid depression is important while treating NP, and venlafaxine may be effective, especially in cases of comorbid ADHD/ASD. Screening for developmental disorders and depression is required in patients with abdominal NP.

Attention Deficit Hyperactivity Disorder, Cannabis Use, and the Endocannabinoid System: A Scoping Review.

There is emerging evidence that the endocannabinoid system (ECS) plays a significant role in the pathophysiology of many psychiatric disorders, including attention deficit hyperactivity disorder (ADHD). Increasing evidence suggests that a number of neurobiological correlates between endogenous cannabinoid function and cognitive dysfunction are seen in ADHD, making the ECS a possible target for therapeutic interventions. Cannabis use and cannabis use disorder are more prevalent in individuals with ADHD, compared to the general population, and there is growing popular perception that cannabis is therapeutic for ADHD. However, the relationship between cannabis use and ADHD symptomology is poorly understood. Further understanding of the role of the ECS in ADHD pathophysiology and the molecular alterations that may be a target for treatment is needed. To further the science on this emerging area of research, this scoping review describes the preclinical and clinical evidence seeking to understand the relationship between the ECS and ADHD.

Medication management and electrocardiogram screening in children with attention deficit hyperactivity disorder.

BACKGROUND: To quantify the proportion of referrals sent to Crumlin Cardiology Department for cardiac screening prior to commencement or modifying attention deficit hyperactivity disorder medication and assess the number detected with a clinically significant abnormality. METHODS: A prospective audit was performed over a 6-month period, from November 2021 to April 2022 inclusive. Referrals sent via outpatient department triage letters, electrocardiogram dept. email, and walk-in electrocardiogram service were screened for those pertaining to commencing or modifying medication for children with attention deficit hyperactivity disorder. Each referral was coded against National Institute for Health and Care Excellence guidelines to determine the degree of clinical details given. Reported abnormalities, recommended management, and correspondence were recorded. RESULTS: Ninety-one referrals were received during the 6-month audit period. More than half lacked a clinical indication for referral (53/91, 58.2%), with fewer than one third (26/91, 28.5%) meeting National Institute for Health and Care Excellence criteria for referral for cardiology. Eighty (80/91) referrals had clinical outcomes available for review (missing outpatient department information and age outside of service range accounted for eleven referrals with unavailable clinical outcomes). Of the eighty clinically reviewed referrals, seventy-two (72/80, 90%) were reported as normal with no cardiology follow up required. Eight referrals (8/80, 10%) were reviewed in the Cardiology Outpatient Department prior to commencement or modifying attention deficit hyperactivity disorder medication. Of these, only one (1/80 1%) had a clinically significant abnormality which was a potential contraindication to attention deficit hyperactivity disorder medication use, and this referral was appropriate as per National Institute for Health and Care Excellence guidelines. CONCLUSION: Routine screening prior to attention deficit hyperactivity disorder medication prescription in the absence of clinical indications (as per National Institute for Health and Care Excellence) contributed to delays in medication initiation among young people with attention deficit hyperactivity disorder. Unnecessary referrals have resource implications for cardiology clinical team. Improved adherence to National Institute for Health and Care Excellence guidelines would provide benefits for patients and clinicians.

ADHD: prevalence and effect on opioid use disorder treatment outcome in a French sample of patients receiving medication for opioid use disorder-the influence of impulsivity as a mediating factor.

BACKGROUND: Opioid use disorder (OUD) poses a global health challenge, and despite medications for opioid use disorder (MOUD) and psychosocial interventions, relapse remains a significant concern. Comorbid psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), are one of the major factors associated with poor OUD treatment outcome. We aimed to estimate the frequency of probable ADHD (in childhood and in adulthood) in patients with OUD; to assess the factors associated with this comorbidity; and to explore the factors that mediate the relationship between ADHD and OUD treatment outcome. METHODS: We conducted an observational study using a sample of 229 patients aged 18 years and older who were diagnosed with OUD and had received MOUD for at least six months. Participants were assessed through a structured interview and self-report questionnaires. Multivariate logistic regressions and a mediation analysis were performed. RESULTS: Almost half of the participants reported probable ADHD in childhood, and ADHD persisted into adulthood among two-thirds of the patients. The factors associated with poor OUD treatment outcome included earlier onset of OUD, lower education, and greater impulsivity. There was no direct effect of probable ADHD in childhood on OUD treatment outcome, but there was an indirect effect through negative urgency, the tendency to respond impulsively to negatively connoted emotional experiences. CONCLUSIONS: The findings suggest that ADHD symptoms, particularly impulsivity, may contribute to vulnerability in opioid use and play a crucial role in treatment outcomes for this population. TRIAL REGISTRATION: ClinicalTrials identifier NCT01847729.

Methylphenidate and the risk of acute central nervous system oxygen toxicity: a rodent model and observational data in human divers.

Introduction: The effects of methylphenidate, a stimulant often prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD), on the development of central nervous system oxygen toxicity (COT) have not been experimentally evaluated. Methods: The records of all pure-oxygen-rebreather divers evaluated at our institution from 1975-2022 were assessed. Cases of COT were defined as a new onset of tinnitus, tunnel vision, myoclonus, headache, nausea, loss of consciousness, or seizures resolving within 15 minutes from breathing normobaric air, and matched 4:1 with similar controls. Any medications issued to the diver in the preceding three months, including methylphenidate, were recorded. In the animal arm of this study, male mice were exposed to increasing doses of methylphenidate orally, with subsequent exposure to hyperbaric O2 until clinically evident seizures were recorded. Results: Seventy-five cases of COT were identified in divers, occurring at a median of 80 (range 2-240) minutes after dive initiation at a median depth of 5 m (2-13). Hypercarbia was documented in 11 (14.7%) cases. Prescription of methylphenidate in the preceding three months was not associated with increased risk (OR 0.72, 95% CI 0.16-3.32) of COT. In mice, increasing methylphenidate exposure dose was associated with significantly longer mean COT latency time being 877 s (95% CI 711-1,043) with doses of 0 mg·kg⁻¹; 1,312 s (95% CI 850-1,773) when given 0.75 mg·kg⁻¹; and 1,500 s (95% CI 988-2,012) with 5 mg·kg⁻¹ (F = 4.635, P = 0.014). Conclusions: Observational human data did not demonstrate an association between methylphenidate and an increased risk of COT. Methylphenidate exposure in mice prolongs COT latency and may have protective effects against COT.

The Clinical Utility of Finding Unexpected Subclinical Spikes Detected by High-Density EEG During Neurodiagnostic Investigations.

This study aimed to analyze the frequency of unexpected subclinical spikes (USCS) in pediatric patients who underwent high-density electroencephalogram (HD-EEG). Of the 4481 successful HD-EEG studies, 18.5% (829) were abnormal, and 49.7% of these abnormal studies showed SCS, of which 64.1% were USCS. USCS were found to be correlated with attention/concentration deficits and executive dysfunction, often accompanied by the dual psychiatric diagnosis of ADHD. MRI revealed abnormal findings in 32.6% of the subjects with USCS, such as abnormal signal or signal hyperintensity in brain parenchyma, temporal or arachnoid cysts, and vascular malformations. Moreover, the USCS group who received neuropsychiatric testing scored lower than the population mean on Full-Scale Intelligence Quotient, Working Memory Index, and Processing Speed Index. This study highlights the potential of USCS as biomarkers that can lead to changes in clinical management and outcomes, provide valuable information about pathophysiological mechanisms, and suggest potential treatment pathways.

Effect of ginseng and ginsenosides on attention deficit hyperactivity disorder: A systematic review.

Attention deficit hyperactivity disorder (ADHD) is a rapidly increasing neurodevelopmental disorder but currently available treatments are associated with abuse risk, side effects, and incomplete symptom relief. There is growing interest in exploring complementary options, and ginseng has gained attention for its therapeutic potential. This systematic review aimed to assess current evidence on the efficacy of ginseng and its active components, ginsenosides, for ADHD. Eligible studies were identified through searches of PubMed, Embase, Cochrane Library, and Web of Science, up to June 2023. The inclusion criteria included both human and animal studies that investigated the effects of ginseng or ginsenosides on ADHD. The risk of bias was assessed according to study type. Six human studies and three animal studies met the inclusion criteria. The results suggest that ginseng and ginsenosides may have beneficial effects on ADHD symptoms, particularly inattention, through dopaminergic/norepinephrinergicmodulation and BDNF/TrkB signaling. Ginseng and ginsenosides have promising potential for ADHD treatment. Due to limitations in evidence quality, such as the risk of bias and variability in study designs, larger controlled studies are essential. Integrating ginseng into ADHD management may have valuable implications for individuals seeking well-tolerated alternatives or adjunctive therapies.

Associating prenatal antibiotics exposure with attention deficit hyperactivity disorder symptoms in preschool children: The role of maternal vitamin D.

BACKGROUND: The associations between prenatal antibiotics exposure and attention-deficit/hyperactivity disorder (ADHD) in preschoolers, and the role of maternal vitamin D in these associations, remain to be explored. OBJECTIVES: To evaluate the relationships between multiple maternal urinary antibiotics levels and preschoolers' ADHD symptoms, and to identify the potential modifying effects of maternal vitamin D. METHODS: Based on a prospective birth cohort, the present study included 2033 motherchild pairs. Maternal urine and serum samples were collected during all three trimesters to measure the urinary concentrations of 43 antibiotics (including two metabolites) and the serum vitamin D levels. The ADHD symptoms of preschoolers were assessed using the Diagnostic and Statistical Manual-oriented ADHD problems scale in the Achenbach Child Behavior Checklist. Multiple informant models in the form of logistic regression were conducted to investigate the associations between prenatal antibiotics exposure and preschooler ADHD symptoms, and these associations were stratified by child sex and maternal vitamin D status. RESULTS: Compared with the lowest tertile concentrations, maternal exposure to the middle tertile concentrations of doxycycline and human antibiotics/preferred as human antibiotics (HAs/PHAs), and the highest tertile concentrations of doxycycline during the first trimester were associated with an increased risk of ADHD symptoms in children. An increased risk of ADHD symptoms was observed in girls exposed to the highest tertile levels of sulfamethazine during the second trimester. Furthermore, pregnant women with vitamin D deficiency have a greater risk of ADHD symptoms in their offspring after exposure to doxycycline in the first trimester. CONCLUSIONS: Maternal exposure to doxycycline and HAs/PHAs during the first trimester increases the risk of ADHD symptoms in preschoolers. Mid-pregnancy sulfamethazine exposure increases the risk of ADHD symptoms in girls. Maternal vitamin D deficiency during pregnancy may exacerbate the adverse effects of doxycycline exposure on ADHD symptoms.

Exploring the quantity and quality of symptoms of attention deficit hyperactivity disorder and intelligence in children with cerebral palsy: a case-control study.

To evaluate whether attention deficit hyperactivity disorder (ADHD) symptoms differ across cerebral palsy (CP) and the relationship of these symptoms to CP disease data. Each of the three groups (CP, ADHD, and control) included 22 volunteers, aged 6-18. The CP group was divided into two groups, with and without ADHD (CP + ADHD and CP-ADHD). The groups were compared in terms of clinical data, ADHD symptoms, and intelligence levels. ADHD was reported in 36.4% of the CP group and 9.1% of the control group (p = 0.031). The rate of moderate/severe motor disability was higher (p = 0.052), and the Wechsler Intelligence Scale for Children-Revised (WISC-R) (total, performance, verbal) scores were lower in the CP + ADHD group compared to the CP-ADHD group (p = 0.005, p = 0.005, p = 0.002). Cognitive problems/inattention scores were higher in the CP group compared to the control group (p = 0.015). WISC-R (total, performance, verbal) scores were lower in the CP group compared to the ADHD group (p = 0.008, p = 0.001, p = 0.047) and the control group (p < 0.001, p < 0.001, p = 0.001). CONCLUSION: ADHD is more common in CP and may be seen in a predominantly inattentive presentation. It is related to a worse motor disability and intelligence level in CP. WHAT IS KNOWN: • Compared to the general population, ADHD is reported to be more common in children with CP. WHAT IS NEW: • ADHD may be seen in a predominantly inattentive presentation rather than the other presentations in children with CP. • ADHD is related to a worse motor disability and intelligence level in CP.

Role of vesicular monoamine transporter-2 for treating attention deficit hyperactivity disorder: a review.

RATIONALE: The Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) classifies attention deficit hyperactivity disorder (ADHD) as a neurodevelopmental disorder that interferes with human functioning and development. As the clinical presentation of ADHD involves a deficiency in executive function, neurocognitive deficits involving distinctive neuropathological changes must be present for clinical diagnosis. OBJECTIVES: The vesicular monoamine transporter (VMAT), specifically VMAT-2, plays a role in ADHD pathogenesis. In addition, experimental data show that the stimulants (amphetamines and methylphenidate) are first-line treatments for the condition because of their extensive interaction with VMAT-2. The interactions of peptides, bupropion, and nutritional supplements with VMAT-2 receptors have been researched, but more evidence is needed to elucidate their pharmacodynamic properties. Therefore, this literature review evaluated the current pharmacological treatment modalities, peptides, and nutritional supplements for ADHD that target the VMAT-2 system. METHODS, RESULTS, AND CONCLUSIONS: We obtained relevant studies from several platforms, including the National Center for Biotechnology, Clinical Key, Access Medicine, and PubMed. From the results of these studies, we observed that stimulants interact highly with the VMAT-2 transporter, with omega-3 fatty acids, peptides, and bupropion exerting some modulatory activity on VMAT-2. These agents should be considered for the future treatment of ADHD, although clinical-level research involving human participants is necessary.