Comparative Pharmacokinetics Research of 13 Bioactive Components of Jieyu Pills in Control and Attention Deficit Hyperactivity Disorder Model Rats Based on UPLC-Orbitrap Fusion MS.

Jieyu Pills (JYPs), a Chinese medicine consisting of 10 herbal elements, have displayed promising clinical effectiveness and low by-effects in the treatment of depression. Prior investigations mostly focused on elucidating the mechanism and therapeutic efficacy of JYPs. In our earlier study, we provided an analysis of the chemical composition, serum pharmacochemistry, and concentrations of the main bioactive chemicals found in JYPs. However, our precise understanding of the pharmacokinetics and metabolism remained vague. This study involved a comprehensive and meticulous examination of the pharmacokinetics of 13 bioactive compounds in JYPs. Using UPLC-Orbitrap Fusion MS, we analyzed the metabolic characteristics and established the pharmacokinetic parameters in both control rats and model rats with attention deficit hyperactivity disorder (ADHD) following oral administration of the drug. Before analysis, plasma samples that were collected at different time intervals after the administration underwent methanol pre-treatment with Puerarin used as the internal standard (IS) solution. Subsequently, the sample was chromatographed on a C18 column employing gradient elution. The mobile phase consisted of methanol solution containing 0.1% formic acid in water. The electrospray ionization source (ESI) was utilized for ionization, whereas the scanning mode employed was selected ion monitoring (SIM). The UPLC-Orbitrap Fusion MS method was subjected to a comprehensive validation process to assess its performance. The method demonstrated excellent linearity (r ≥ 0.9944), precise measurements (RSD < 8.78%), accurate results (RE: -7.88% to 8.98%), and appropriate extraction recoveries (87.83-102.23%). Additionally, the method exhibited minimal matrix effects (87.58-101.08%) and satisfactory stability (RSD: 1.52-12.42%). These results demonstrated adherence to the criteria for evaluating and determining biological material. The 13 bioactive compounds exhibited unique pharmacokinetic patterns in vivo. In control rats, all bioactive compounds except Ferulic acid exhibited linear pharmacokinetics within the dose ranges. In the ADHD model, the absorption rate and amount of most of the components were both observed to have increased. Essentially, this work is an important reference for examining the metabolism of JYPs and providing guidelines for clinical therapy.

New horizons for the study of saffron (Crocus sativus L.) and its active ingredients in the management of neurological and psychiatric disorders: A systematic review of clinical evidence and mechanisms.

Saffron (Crocus sativus), as an herbal medicine, has been extensively investigated for treating neurological and psychiatric disorders. This systematic review aimed to assess the overall effects of saffron on cognition, depression, anxiety, sleep disorders, attention-deficit/hyperactivity disorder (ADHD), and obsessive-compulsive disorder (OCD). Relevant randomized controlled trials (RCTs) were identified by searching PubMed/Medline, Web of Science, and Clinical Trials databases up to June 2023 according to search terms and inclusion criteria. The participants were either healthy or suffering from some diseases, including neurological and psychiatric disorders, and consumed saffron or its extracts as an intervention. The risk of bias was assessed according to the Cochrane guidelines, and the PRISMA statement was followed. The meta-analysis was performed using RevMan and STATA software. A random-effects or fixed-effects model was used to calculate the pooled effect sizes. Forty-six RCTs were enrolled, and the duration of these trials ranged from 4 to 48 weeks with saffron or its extracts, both alone or in combination with conventional drugs. Saffron was more effective than placebo in improving cognition, depression with an overall effect size of -4.26 (95% CI: -5.76, -2.77), anxiety of -3.75 (95% CI: -5.83, -1.67), and sleep disorders of -1.91 (95% CI: -2.88, -0.93). Saffron was non-inferior to conventional drugs for treating cognitive disorders, depression, anxiety, ADHD, and OCD, and it exhibited good tolerance with few side effects. Saffron may exert protective roles for neurological and psychiatric disorders and represents a relatively favorable and safe treatment.

Phosphatidylserine enriched with polyunsaturated n-3 fatty acid supplementation for attention-deficit hyperactivity disorder in children and adolescents with epilepsy: A randomized placebo-controlled trial.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a frequent comorbidity in children with epilepsy, which management mostly relies on the usual treatments of ADHD, especially methylphenidate. Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed as an alternative therapeutic approach in ADHD without epilepsy but has never been evaluated in epilepsy-associated ADHD. METHODS: A multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA, in eicosapentaenoic- and docosahexaenoic-acid form, conjugated to a phospholipid vector (PS-Omega3) in children aged >6 and <16-years old, and suffering from any type of epilepsy and ADHD (inattentive or combined type) according to DSM-V. After a 4-week baseline period, patients were allocated (1:1) either to placebo group or to PS-Omega 3 group and entered a 12 week-double-blind treatment period which was followed by a 12 week-open-label treatment period. The primary outcome was the reduction of the ADHD-rating scale IV attention-deficit subscore after 12 weeks of treatment. RESULTS: The study was stopped early because of lack of eligible participants and the expected sample size was not reached. Seventy-four patients were randomized, 44 in PS-Omega3, and 30 in the placebo group. The reduction after 12 weeks of treatment in the inattention subscore of the ADHD-IV scale was -1.57 in the PS-Omega3 group, and -2.90 in the placebo group (p = 0.33, α = 5%). Results were similar after 24 weeks of treatment and for all other ADHD-related secondary outcomes, with no difference between placebo and PS-Omega3. CONCLUSION: Our study remaining underpowered, no formal conclusion about the effect of Ps-Omega3 could be drawn. However, our data strongly suggested that the PS-Omega 3 formulation used in the current study did not improve ADHD symptoms in children with epilepsy. PLAIN LANGUAGE SUMMARY: Supplementation with polyunsaturated n-3 Fatty Acid (PUFA) has been proposed in ADHD but has never been evaluated in patients with both epilepsy and ADHD. To address this issue, we conducted a multicenter double blind randomized placebo-controlled trial evaluating supplementation with PUFA in children with epilepsy and ADHD. The study was stopped early because of lack of eligible participants, hampering formal conclusion. However, the evolution of the ADHD symptoms at 12 and 24 weeks did not differ between placebo and PUFA supplementation, strongly suggesting that PUFA did not improve ADHD symptoms in children with epilepsy.

Treatment response to supplemental nutrients for ADHD is independent of diet quality: the MADDY Study RCT.

OBJECTIVES: The 8-week Micronutrients for ADHD in Youth (MADDY) randomized controlled trial (N = 126, age 6-12) of broad-spectrum multinutrients for ADHD with emotional dysregulation found 3 times as many responders with multinutrients (54%) compared to placebo (18%) by Clinical Global Impression-Improvement (CGI-I). Our primary aim for this analysis tests the hypothesis that those with poor overall diet quality at baseline benefit more. The second aim is to explore whether specific components of diet quality moderate treatment response. METHODS: 124 children (69 multinutrients, 55 placebo) had diet quality assessed using the Healthy Eating Index-2015 (HEI-2015). For each potential moderator, the outcome CGI-I at week 8 (RCT-end), was modeled two ways: (1) as a dichotomous variable: responder/non-responder, with responders defined by a rating of 1 or 2 'very much' or 'much improved,' all else equals non-responder using logistic regression, and (2) as a dimensional improvement outcome from 1 = very much improved to 7 = very much worse, using linear regression. RESULTS: HEI-2015 total score did not moderate treatment response [odds ratio = 1.00 (95% CI: 0.90,1.10), p = 0.984] or improvement [ß = -0.01 (95% CI: -0.06,0.04), p = 0.648]. However, total vegetable intake moderated level of improvement in exploratory analysis [ß = -0.48 (95% CI: -0.82, -0.13), p = 0.007]: those with higher baseline vegetable intake showed greater benefit from multinutrients compared to placebo. CONCLUSIONS: Multinutrients may benefit children with ADHD and irritability regardless of overall diet quality. The finding that higher baseline vegetable intake may improve response to multinutrients deserves further exploration, including dietary effect on gut microbiota and absorption of multinutrients and parental factors.

COVID-19 and Adolescent Outpatient Mental Health Service Utilization.

OBJECTIVE: The COVID-19 pandemic created challenges in accessing mental health (MH) services when adolescent well-being declined. Still, little is known about how the COVID-19 pandemic affected outpatient MH service utilization for adolescents. METHODS: Retrospective data were collected from electronic medical records of adolescents aged 12-17 years at Kaiser Permanente Mid-Atlantic States, an integrated health care system from January 2019 to December 2021. MH diagnoses included anxiety, mood disorder/depression, anxiety and mood disorder/depression, attention-deficit/hyperactivity disorder, or psychosis. We used interrupted time series analysis to compare MH visits and psychopharmaceutical prescribing before and after the COVID-19 onset. Analyses were stratified by demographics and visit modality. RESULTS: The study population of 8121 adolescents with MH visits resulted in a total of 61,971 (28.1%) of the 220,271 outpatient visits associated with an MH diagnosis. During 15,771 (7.2%) adolescent outpatient visits psychotropic medications were prescribed. The increasing rate of MH visits prior to COVID-19 was unaffected by COVID-19 onset; however, in-person visits declined by 230.5 visits per week (P < .001) from 274.5 visits per week coupled with a rise in virtual modalities. Rates of MH visits during the COVID-19 pandemic differed by sex, mental health diagnosis, and racial and ethnic identity. Psychopharmaceutical prescribing during MH visits declined beyond expected values by a mean of 32.8 visits per week (P < .001) at the start of the COVID-19 pandemic. CONCLUSIONS: A sustained switch to virtual visits highlights a new paradigm in care modalities for adolescents. Psychopharmaceutical prescribing declined requiring further qualitative assessments to improve the quality of access for adolescent MH.

A Randomized Three-Arm Double-Blind Placebo-Controlled Study of Homeopathic Treatment of Children and Youth with Attention-Deficit/Hyperactivity Disorder.

Objectives: Approximately 30% of children diagnosed with attention-deficit/hyperactivity disorder (ADHD), the most prevalent mental health disorder in children worldwide, do not respond to conventional pharmaceutical treatments. Previous studies of homeopathic treatment for ADHD have been inconclusive. The objectives of this study were to determine if there (a) is an overall effect of homeopathic treatment (homeopathic medicines plus consultation) in the treatment of ADHD; (b) are any specific effects the homeopathic consultation alone in the treatment of ADHD; and (c) are any specific effects of homeopathic medicines in the treatment of ADHD. Design: The design was a randomized double-blind placebo-controlled clinical trial. Setting/Location: Toronto, Canada. Subjects: Children aged 6-16 years diagnosed with ADHD. Interventions: Participants were randomized to one of three arms: Arm 1 (Remedy and Consultation); Arm 2 (Placebo and Consultation); or Arm 3 (Usual Care). Outcome Measures: Primary Outcome was the change of CGI-P T score between baseline and 28 weeks. Results: There was an improvement in ADHD symptoms as measured by the Conner 3 Global Index-Parent T-score in the two groups (Arms 1 and 2) that received consultations with a homeopathic practitioner when compared with the usual care control group (Arm 3). Parents of the children in the study who received homeopathic consultations (Arms 1 and 2) also reported greater coping efficacy compared with those receiving usual care (Arm 3). There was no difference in adverse events among the three study arms. Conclusions: In this study, homeopathic consultations provided over 8 months with the use of homeopathic remedy was associated with a decrease in ADHD symptoms in children aging 6-16 years when compared with usual treatment alone. Children treated with homeopathic consultations and placebo experienced a similar decrease in ADHD symptoms; however, this finding did not reach statistical significance when correcting for multiple comparisons. Homeopathic remedies in and of themselves were not associated with any change in ADHD symptoms. Clinical Trial Registration: This trial was registered on ClinicalTrials.gov; NCT02086864.

Hypnosis therapy for self-esteem in pediatric neurology practice: A pilot exploratory study.

BACKGROUND: A number of pediatric conditions are chronic, such as attention-deficit/hyperactivity disorder (ADHD), idiopathic epilepsies, or anxiety disorder. They all have an impact on self-esteem with consequences on the quality of life. Hypnosis is a therapeutic strategy that consists in putting into trance an individual who becomes receptive to appropriate suggestions. Such an approach is now considered a simple and safe therapy with limited cost. The aim of the present study was to show the feasibility of hypnosis for improving self-esteem in children with the aforementioned conditions. METHODS: We conducted a single-center study with prospectively collected data during routine care. Patients with ADHD, idiopathic epilepsies, or anxiety disorder and a low self-esteem were included between April 2018 and February 2020. They all underwent the same hypnosis protocol conducted by the same therapist. Self-esteem was assessed using two self-evaluation scales, the Jodoin 40 scale and Piers-Harris Self-Concept Scale, and a self-assigned self-esteem score at the beginning and at the end of the hypnosis session. RESULTS: Among the 14 children included, 11 were studied (6 ADHD, 1 anxiety disorder, 4 idiopathic epilepsies). The median age at inclusion was 12.2 years and the sex ratio was 4:3 (boys:girls). Final comparisons showed that self-esteem had improved, which was statistically significant regarding the Jodoin 40 scale and the self-assigned self-esteem score (p ≤ 0.05). Neither side effect nor disease worsening was observed. CONCLUSION: This study illustrates the feasibility of therapeutic hypnosis in clinical practice for improving self-esteem in chronic pediatric conditions.

Exploring the Relationship between Adherence to Therapy, Treatment Acceptability, and Clinical Outcomes in Adults with Attention-Deficit/Hyperactivity Disorder: Results from the COMPAS Multicenter Randomized Controlled Trial.

INTRODUCTION: Cognitive behavioral therapy and dialectical behavior therapy (DBT) can be effective in treating adults with ADHD, and patients generally consider these interventions useful. While adherence, as measured by attendance at sessions, is mostly sufficient, adherence to therapy skills has not been assessed. Furthermore, the relationship between patient evaluation of therapy effectiveness, treatment adherence, and clinical outcomes is understudied. OBJECTIVE: This study aimed to examine treatment acceptability and adherence in relation to treatment outcomes in a large randomized controlled trial comparing a DBT-based intervention with a nonspecific active comparison, combined with methylphenidate or placebo. METHOD: A total of 433 adult patients with ADHD were randomized. Participants reported how effective they found the therapy, and adherence was measured by attendance at therapy sessions and by self-reports. Descriptive, between-groups, and linear mixed model analyses were conducted. RESULTS: Participants rated psychotherapy as moderately effective, attended 78.40-94.37% of sessions, and used skills regularly. The best-accepted skills were sports and mindfulness. Groups receiving placebo and/or nonspecific clinical management rated their health condition and the medication effectiveness significantly worse than the psychotherapy and methylphenidate groups. Improvements in clinical outcomes were significantly associated with treatment acceptability. Subjective (self-reported) adherence to psychotherapy was significantly associated with improvements in ADHD symptoms, clinical global efficacy and response to treatment. DISCUSSION: These results further support the acceptability of DBT for adult ADHD and suggest the need to address adherence to treatment to maximize clinical improvements. Results may be limited by the retrospective assessment of treatment acceptability and adherence using an ad hoc instrument.

UK Medical Cannabis Registry: An analysis of clinical outcomes of medicinal cannabis therapy for attention-deficit/hyperactivity disorder.

AIM: This study aims to analyze the health-related quality of life (HRQoL) and safety outcomes in attention-deficit/hyperactivity disorder (ADHD) patients treated with cannabis-based medicinal products (CBMPs). METHODS: Patients were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in the following patient-reported outcome measures (PROMs) at 1, 3, 6, and 12 months from baseline: EQ-5D-5L index value, generalized anxiety disorder-7 (GAD-7) questionnaire, and the single-item sleep quality score (SQS). Secondary outcomes assessed the incidence of adverse events. Statistical significance was defined as p < 0.050. RESULTS: Sixty-eight patients met the inclusion criteria. Significant improvements were identified in general HRQoL assessed by EQ-5D-5L index value at 1, 3, and 6 months (p < 0.050). Improvements were also identified in GAD-7 and SQS scores at 1, 3, 6, and 12 months (p < 0.010). 61 (89.71%) adverse events were recorded by 11 (16.18%) participants, of which most were moderate (n = 26, 38.24%). CONCLUSION: An association between CBMP treatment and improvements in anxiety, sleep quality, and general HRQoL was observed in patients with ADHD. Treatment was well tolerated at 12 months. Results must be interpreted with caution as a causative effect cannot be proven. These results, however, do provide additional support for future evaluation within randomized controlled trials.

Assessment of probiotic strain Lactobacillus acidophilus LB supplementation as adjunctive management of attention-deficit hyperactivity disorder in children and adolescents: a randomized controlled clinical trial.

BACKGROUND: This study was designed to examine the possible efficacy of the probiotic strain Lactobacillus acidophilus LB (Lacteol Fort) on attention-deficit/hyperactivity disorder (ADHD) symptomatology and evaluate its influence on cognition function. METHODS: In this randomized controlled trial, 80 children and adolescents with ADHD diagnosis, aged 6-16 years, were included. The participants were randomly assigned to two groups: one group received probiotics plus atomoxetine, whereas the other group received atomoxetine only. ADHD symptomatology was assessed using the Conners Parent Rating Scale-Revised Long Version (CPRS-R-L) and Child Behavioral Checklist (CBCL/6-18). The participants were evaluated for their vigilance and executive function using Conner's Continuous Performance Test (CPT) and Wisconsin Card Sort Test (WCST). Both groups were assessed at the beginning of the study and the end of the twelve weeks. RESULTS: The probiotic group comprised 36 patients, whereas the control group comprised 40 patients in the final analysis after four patients dropped out of the trial. After 3 months of probiotic supplementation, a significant improvement in the CPRS-R-L and CBCL total T scores was observed compared with those in the control group (p = 0.032, 0.024, respectively). Additionally, the probiotic group demonstrated improved focus attention (target accuracy rate and omission errors;p = 0.02, 0.043, respectively) compared with the control group. An analysis of the Wisconsin Card Sorting Test (WCST) performance demonstrated that the probiotic group had significantly lower perseverative (p = 0.017) and non-perseverative errors (p = 0.044) but no significant differences compared to the control group. CONCLUSION: Lactobacillus acidophilus LB supplementation combined with atomoxetine for 3 months had a beneficial impact on ADHD symptomology and a favorable influence on cognitive performance. As a result, the efficacy of probiotics as an adjunctive treatment for managing ADHD may be promising. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT04167995). Registration date: 19-11-2019.

Effect of 25 hydroxyvitamin D on attention deficit and hyperactivity in school-age children with ADHD.

BACKGROUND: To observe the serum levels of 25 hydroxyvitamin D [25 (OH) D] in healthy school-age children and children with attention deficit hyperactivity disorder (ADHD) and to analyze the effects of serum 25 (OH) D on the symptoms of attention deficit and hyperactivity in school-age children with ADHD. METHODS: According to the Diagnostic and Statistical Manual of Mental Disorders DSM-IV diagnostic criteria for ADHD in children, 80 healthy children aged 6 years or less than 10 years old and children diagnosed with ADHD in the Department of Rehabilitation Medicine, Department of Pediatrics and Department of Physical Examination of our hospital were randomly selected as research subjects. The serum 25 (OH) D level, attention deficit hyperactivity (Swanson, Nolan, and Pelham, version IV [SNAP-IV] parental version) score and Conners child behavior (PSQ) index were observed and compared between the 2 groups. In addition, the children with ADHD whose serum 25 (OH) D was lower than normal were treated with supplemental VitD3, and the changes in serum 25 (OH) D, SNAP-IV parental score and PSQ index of ADHD children were observed and compared. RESULTS: Serum 25(OH)D was insufficient or deficient in 26 healthy children, but the SNAP-IV score and PSQ index were normal. Serum 25(OH)D was lower than normal in 69 patients in the ADHD group, which was negatively correlated with SNAP-IV score (r = -0.3479, P = .0034) and negatively correlated with PSQ index (r = -0.3566, P = .0026). After vitamin D3 (VitD3) supplementation in 69 children with serum 25(OH)D levels lower than the normal ADHD group, it was found that the SNAP-IV score (r = -0.4654, P = .0037) and PSQ index (r = -0.5680, P = .0002) of 34 children with ADHD were negatively correlated with the increase in serum 25(OH)D. The SNAP-IV score and PSQ index of the other 35 children with ADHD showed no correlation with the increase in serum 25 (OH) D (P > .05). CONCLUSION SUBSECTIONS: Serum 25(OH)D levels lower than normal are more common in school-age children, and levels lower than normal are not the key pathogenic factor of ADHD in school-age children, but serum 25(OH)D levels lower than normal may be the upregulation factor of attention deficit and hyperactivity disorder expression in some school-age children with ADHD. The lower level of serum 25(OH)D may be closely related to the severity of ADHD symptoms in some children.

Omega-3 Polyunsaturated Fatty Acids for Core Symptoms of Attention-Deficit/Hyperactivity Disorder: A Meta-Analysis of Randomized Controlled Trials.

Objective: Previous studies have shown conflicting results for the effectiveness of omega-3 polyunsaturated fatty acids (PUFAs) in improving attention-deficit/hyperactivity disorder (ADHD) symptoms. This inconsistency may be due to differences in dosage, composition, and treatment duration. The current meta-analysis aims to address this inconsistency by improving subtype analyses and focusing on heterogeneity in treatment duration, omega-3 PUFA composition, and eicosapentaenoic acid (EPA) dose.Data Sources and Study Selection: We searched PubMed, EMBASE, PsycINFO, and Cochrane Library for randomized controlled trials of omega-3 PUFAs for ADHD, without publication year or language limitations, up to November 27, 2022. The primary outcome was the improvement of ADHD core symptoms. Subgroup analyses were conducted based on the formula, dosages, and composition ratios of omega-3 PUFAs. To ensure methodological quality, the Cochrane Risk-of-Bias Tool 1.0 was utilized to assess the risk of bias for each study included in the analysis. The pooled data were then analyzed using the random-effect meta-analysis, and the inverse variance method was employed.Data Extraction: The outcomes of interest were extracted using a data extraction form developed for this study.Results: Twenty-two studies with 1,789 participants were included in the analysis. Overall, omega-3 PUFAs did not significantly improve ADHD core symptoms compared to placebo (standardized mean difference [SMD]: -0.16; 95% CI, -0.34 to 0.01; P = .07). However, in the subgroup of studies with a treatment duration of at least 4 months, omega-3 PUFAs were significantly more effective than placebo (SMD: -0.35; 95% CI,-0.61 to -0.09; P = .007). Neither high eicosapentaenoic acid (EPA) dosage nor high EPA/docosahexaenoic acid (DHA) ratio was found to improve ADHD symptoms.Conclusions: Our findings indicate that omega-3 PUFAs did not improve ADHD core symptoms, but long-term supplementation may have potential benefits. The main limitation of the study was the moderate heterogeneity and small sample sizes in subgroup analyses and the lack of dietary pattern information.

Dosages of Nutrient Supplements and Potential Long-Term Toxicity in Attention-Deficit/Hyperactivity Disorder Micronutrient Study.

We read with interest the article by Johnstone et al.1 reporting their vitamin-mineral randomized trial that found that children with attention-deficit/hyperactivity disorder (ADHD) showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Because some of the mineral dosing was in potentially toxic ranges, we sought to examine the trial findings. Given that the producing company is promoting their supplement for long-term use,2 the scientific and consumer communities might value some additional information about potential toxicity from long-term dosing.

Attention-deficit/hyperactivity disorder (ADHD) symptoms and their relation to diagnosed ADHD, sociodemographic characteristics, and substance use among patients receiving opioid agonist therapy: a Norwegian cohort study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms may challenge sufficient treatment of substance use and mental disorders. The literature on the extent of such symptoms among patients receiving opioid agonist therapy (OAT) is scarce. This study examined ADHD symptoms using the ADHD self-report scale (ASRS) and the association between the 'ASRS-memory' and 'ASRS-attention' scores and substance use and sociodemographic characteristics among patients receiving OAT. METHODS: We used data from assessment visits of a cohort of patients in Norway. In total, 701 patients were included from May 2017 to March 2022. All patients responded at least once to two ASRS questions assessing memory and attention, respectively. Ordinal regression analyses were performed to investigate whether the two obtained scores were associated with age, sex, frequent substance use, injecting use, housing status, and educational attainment at baseline, i.e., the first assessment, and over time. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). Additionally, a subsample of 225 patients completed an extended interview, including the ASRS-screener and collection of registered mental disorder diagnoses from the medical records. Standard cutoffs were used to define the presence of each ASRS symptom or a positive ASRS-screener ('ASRS-positive'). RESULTS: At baseline, 428 (61%) and 307 (53%) patients scored over the cutoffs on the 'ASRS-memory' and 'ASRS-attention,' respectively. Frequent cannabis use was associated with higher 'ASRS-memory' (OR: 1.7, 95% CI: 1.1-2.6) and 'ASRS-attention' (1.7, 1.1-2.5) scores compared with less or no use at baseline, though reduced score on the 'ASRS-memory' over time (0.7, 0.6-1.0). At baseline, frequent stimulant use (1.8, 1.0-3.2) and low educational attainment (0.1, 0.0-0.8) were associated with higher 'ASRS-memory' scores. In the subsample fulfilling the ASRS-screener, 45% of the patients were 'ASRS-positive,' of whom 13% with a registered ADHD diagnosis. CONCLUSIONS: Our findings illustrate a relationship between the ASRS-memory and -attention scores and frequent cannabis and stimulant use. Furthermore, nearly half of the subsample was 'ASRS-positive.' Patients receiving OAT might benefit from being further assessed for ADHD, but improved diagnostic methods are required.

Complementary and Integrative Treatments for Attention-Deficit/Hyperactivity Disorder in Youth.

First-line psychopharmacologic and psychosocial treatments for attention-deficit/hyperactivity disorder in children are effective but limited by tolerability and accessibility problems. Many complementary and integrative strategies have been investigated as alternative or adjunctive treatments for the disorder, and the literature has progressed to meta-analyses for several. Although heterogeneity of study methods and risk of bias pervades the literature, we conclude that Omega-3 supplementation, dietary restriction of artificial food colorings, and physical activity can be considered evidence-based. Additionally, meditation, yoga, and sleep hygiene are safe, partially effective, cost effective and sensible adjunctive treatment strategies.

Systematic Review and Meta-Analyses: Safety and Efficacy of Complementary and Alternative Treatments for Pediatric Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Complementary and alternative treatments (CATs) for ADHD have proliferated over the past decade; however, their safety and efficacy remain uncertain. We completed a systematic review and meta-analyses across CAT domains. METHODS: Systematic search and data extraction identified randomized controlled trials for pediatric ADHD (ages 3-19 years) that included probably blind ADHD symptom outcome measures. We evaluated basic (RCT of a CAT compared with sham/placebo, attention/active control, treatment as usual, and waitlist control), complementary (RCTs comparing an evidence-based treatment with a CAT and the same evidence-based treatment), and alternative (evidence-based treatment to CAT) efficacy. Random-effect meta-analyses were conducted when at least 3 blinded studies were identified for a specific CAT domain. RESULTS: Eighty-seven of 2253 nonduplicate screened manuscripts met inclusion criteria. No study reported significantly greater adverse effects for CATs than controls; naturopathy reported fewer adverse effects than evidence-based treatments but did not demonstrate basic efficacy. In the systematic review of basic efficacy, evidence of effectiveness was mixed but replicated previous evidence for the possible efficacy of cognitive training, neurofeedback, and essential fatty acid supplementation for certain patients. With respect to alternative and complementary efficacy, no CAT outperformed or enhanced evidence-based treatments (stimulant medications and behavioral therapy) when replication was required. Individual meta-analyses indicated that cognitive training was the only CAT that demonstrated overall basic efficacy ( SMD = 0.216; p = 0.032). CONCLUSION: Clinicians may cautiously recommend (but monitor) cognitive training when evidence-based treatments are not feasible or effective for a patient. Additional studies are needed to further understand the potential of CAT domains.

Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity, and impulsivity, and is associated with long-term social, academic, and mental health problems. The stimulant medications methylphenidate and amphetamine are the most frequently used treatments for ADHD, but these are not always effective and can be associated with side effects. Clinical and biochemical evidence suggests that deficiencies of polyunsaturated fatty acids (PUFA) could be related to ADHD. Research has shown that children and adolescents with ADHD have significantly lower plasma and blood concentrations of PUFA and, in particular, lower levels of omega-3 PUFA. These findings suggest that PUFA supplementation may reduce the attention and behaviour problems associated with ADHD. This review is an update of a previously published Cochrane Review. Overall, there was little evidence that PUFA supplementation improved symptoms of ADHD in children and adolescents. OBJECTIVES: To compare the efficacy of PUFA to other forms of treatment or placebo in treating the symptoms of ADHD in children and adolescents. SEARCH METHODS: We searched 13 databases and two trials registers up to October 2021. We also checked the reference lists of relevant studies and reviews for additional references. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials that compared PUFA with placebo or PUFA plus alternative therapy (medication, behavioural therapy, or psychotherapy) with the same alternative therapy alone in children and adolescents (aged 18 years and under) diagnosed with ADHD. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcome was severity or improvement of ADHD symptoms. Our secondary outcomes were severity or incidence of behavioural problems; quality of life; severity or incidence of depressive symptoms; severity or incidence of anxiety symptoms; side effects; loss to follow-up; and cost. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 37 trials with more than 2374 participants, of which 24 trials were new to this update. Five trials (seven reports) used a cross-over design, while the remaining 32 trials (52 reports) used a parallel design. Seven trials were conducted in Iran, four each in the USA and Israel, and two each in Australia, Canada, New Zealand, Sweden, and the UK. Single studies were conducted in Brazil, France, Germany, India, Italy, Japan, Mexico, the Netherlands, Singapore, Spain, Sri Lanka, and Taiwan. Of the 36 trials that compared a PUFA to placebo, 19 used an omega-3 PUFA, six used a combined omega-3/omega-6 supplement, and two used an omega-6 PUFA. The nine remaining trials were included in the comparison of PUFA to placebo, but also had the same co-intervention in the PUFA and placebo groups. Of these, four trials compared a combination of omega-3 PUFA plus methylphenidate to methylphenidate. One trial each compared omega-3 PUFA plus atomoxetine to atomoxetine; omega-3 PUFA plus physical training to physical training; and an omega-3 or omega-6 supplement plus methylphenidate to methylphenidate; and two trials compared omega-3 PUFA plus dietary supplement to dietary supplement. Supplements were given for a period of between two weeks and six months. Although we found low-certainty evidence that PUFA compared to placebo may improve ADHD symptoms in the medium term (risk ratio (RR) 1.95, 95% confidence interval (CI) 1.47 to 2.60; 3 studies, 191 participants), there was high-certainty evidence that PUFA had no effect on parent-rated total ADHD symptoms compared to placebo in the medium term (standardised mean difference (SMD) -0.08, 95% CI -0.24 to 0.07; 16 studies, 1166 participants). There was also high-certainty evidence that parent-rated inattention (medium-term: SMD -0.01, 95% CI -0.20 to 0.17; 12 studies, 960 participants) and hyperactivity/impulsivity (medium-term: SMD 0.09, 95% CI -0.04 to 0.23; 10 studies, 869 participants) scores were no different compared to placebo. There was moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups (RR 1.02, 95% CI 0.69 to 1.52; 8 studies, 591 participants). There was also moderate-certainty evidence that medium-term loss to follow-up was likely similar between groups (RR 1.03, 95% CI 0.77 to 1.37; 13 studies, 1121 participants). AUTHORS' CONCLUSIONS: Although we found low-certainty evidence that children and adolescents receiving PUFA may be more likely to improve compared to those receiving placebo, there was high-certainty evidence that PUFA had no effect on total parent-rated ADHD symptoms. There was also high-certainty evidence that inattention and hyperactivity/impulsivity did not differ between PUFA and placebo groups. We found moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups. There was also moderate-certainty evidence that follow-up was similar between groups. It is important that future research addresses the current weaknesses in this area, which include small sample sizes, variability of selection criteria, variability of the type and dosage of supplementation, and short follow-up times.

The association between nonpharmacological interventions and quality of life in children with attention deficit hyperactivity disorder: A systematic review.

BACKGROUND: Attention deficit hyperactivity disorder is a common psychiatric disorder with a worldwide prevalence of about five percent among children and adolescents. This disorder affects most aspects of their lives e.g., academic performance and social relations, and their overall quality of life is reduced compared to healthy peers. The majority of children with ADHD are treated with medication that potentially has an insufficient effect and/or frequently occurring side effects. OBJECTIVES: To enable nurses and other health care professionals to guide children with ADHD and their families in their choices of treatment, based on the best available literature on the association between nonpharmacological interventions and quality of life. DATA SOURCES: A literature search was performed in the databases CENTRAL, Embase, PubMed, CINAHL, and PsycINFO. Seven randomized controlled trials were included in this systematic review. They examined the use of polyunsaturated fatty acids, physical activity, psychoeducation, cognitive therapy, cognitive training, hippotherapy, and behavioral therapy. CONCLUSIONS: The study of behavioral therapy in the form of a sleep intervention detected an improvement in quality of life which was statistically significant compared to the control group. IMPLICATIONS FOR PRACTICE: Children with ADHD and a sleep disorder may gain improvement in their quality of life from a sleep intervention.