A meta-analysis on the therapeutic efficacy of repetitive transcranial magnetic stimulation for cognitive functions in attention-deficit/hyperactivity disorders.

BACKGROUND: Therapeutic efficacies of repetitive transcranial magnetic stimulation (rTMS) for improving cognitive functions in patients with deficit/hyperactivity disorder (ADHD) remained unclear. The aim of this meta-analysis was to investigate the therapeutic efficacy of rTMS focusing on different cognitive performances. METHODS: Major databases were searched electronically from inception to February 2023 by using keywords mainly "rTMS" and "ADHD" to identify randomized controlled trials (RCTs) that investigated the therapeutic efficacy of rTMS for improving cognitive functions assessed by standardized tasks in patients with ADHD. The overall effect size (ES) was calculated as standardized mean difference (SMD) based on a random effects model. RESULTS: Meta-analysis of five RCTs with 189 participants (mean age of 32.78 and 8.53 years in adult and child/adolescent populations, respectively) demonstrated that rTMS was more effective for improving sustained attention in patients with ADHD compared with the control groups (SMD = 0.54, p = 0.001).Our secondary analysis also showed that rTMS was more effective for improving processing speed than the control groups (SMD = 0.59, p = 0.002) but not for enhancing memory or executive function. CONCLUSIONS: Our results supported the therapeutic efficacy of rTMS for improving sustained attention and processing speed. However, the limitation of available data warrants further studies to verify these findings.

Therapeutic effects of antidepressants for global improvement and subdomain symptoms of autism spectrum disorder: a systematic review and meta-analysis.

BACKGROUND: No established pharmacological treatment is available for the core symptoms of autism spectrum disorder (ASD). This study aimed at investigating the efficacy of antidepressants for the core and associated symptoms of ASD. METHODS: We searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science and ClinicalTrials.gov using the keywords "ASD" and "antidepressants." We searched from database inception to June 2021 for randomized controlled trials of antidepressant use in patients with ASD. We calculated pooled effect sizes based on a random-effects model. RESULTS: Analysis of 16 studies with 899 participants showed improvements in restricted and repetitive behaviours (effect size = 0.27) and global symptoms (effect size = 1.0) in patients with ASD taking antidepressants versus those taking placebos (p ≤ 0.01). We found no differences between the 2 groups (p ≥ 0.36) in terms of dropout rate (odds ratio [OR] = 1.17) or rate of study discontinuation because of adverse events (OR = 1.05). We also noted improvements in irritability and hyperactivity in the antidepressant group (Hedges g = 0.33 and 0.22, respectively, both p < 0.03). Subgroup analyses showed significant effects of medication type (i.e., clomipramine was better than SSRIs) and age (antidepressants were more effective in adults than in children or adolescents) on both restricted and repetitive behaviours and global improvement (p < 0.05). Meta-regression demonstrated that better therapeutic effects were associated with lower symptom severity and older age. LIMITATIONS: The small effect sizes and variations in treatment response that we found warrant further study. CONCLUSION: Our results supported the effectiveness of antidepressants for global symptoms and symptom subdomains of ASD, with tolerable adverse effects. Low symptom severity and adulthood were associated with better outcomes.

Exploring the Effects of Pharmacological, Psychosocial, and Alternative/Complementary Interventions in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: Meta-Regression Approach.

BACKGROUND: There have been various therapies for attention-deficit/hyperactivity disorder (ADHD), but the previous meta-analysis of ADHD efficacy remains unclear. This study aims to systemically meta-regress the effect sizes (ES) of psychostimulant pharmacotherapy (methylphenidate and lisdexamfetamine), non-stimulant pharmacotherapy (atomoxetine and alpha-2 agonists), psychosocial therapy (parental behavioral therapy [PBT]), combination therapy (psychostimulant plus PBT), and alternative/complementary interventions to determine the right treatment for ADHD. METHODS: We searched various ADHD interventions from the MEDLINE and PubMed databases (National Center for Biotechnology Information) between January 1, 1980, and July 30, 2018. Following the meta-analysis of random effects, the meta-regression analyses were used to explore factors potentially influencing treatment efficacy. The confounding variables included type of treatment, type of study, age, type of symptom scale used, and year of publication. RESULTS: A total of 107 trials (n = 9883 participants) were included. After adjustment, compared with the psychostimulant therapy (28 trial, 2134 participants), non-stimulant pharmacotherapy (28 trials, 4991 participants) and alternative/complement intervention (25 trials, 1195 participants) were less effective by the ES of -0.384 (P = .004) and -0.419 (P = .028), respectively. However, compared with psychostimulant, PBT (19 trials, 1122 participants; ES = -0.308, P = .095) and the combination of psychostimulant and PBT (7 trials, 441participants; ES = -0.196, P = .209) did not differ significantly. CONCLUSIONS: Psychostimulant therapy surpassed non-stimulant pharmacotherapy and alternative/complement intervention. Psychostimulant therapy, PBT, and the combination of psychostimulant therapy and PBT appear to be similar in efficacy according to this meta-regression.

Treatment Efficacy of Internet Gaming Disorder With Attention Deficit Hyperactivity Disorder and Emotional Dysregulaton.

BACKGROUND: Recent youth with Attention Deficit Hyperactivity Disorder (ADHD) noticed emotional dysregulation if they had Internet Gaming Disorder (IGD). This study aims to understand the treatment efficacy of IGD with ADHD and emotional dysregulaton. METHOD: A total of 101 ADHD youths were recruited. We used the Chen Internet Addiction Scale and IGD criteria of the diagnotsic statistical manual (DSM)-5 to confirm IGD. The Swanson, Nolan, and Pelham questionnaire Version IV was used for symptoms of ADHD and oppositional defiant disorder. Disruptive mood dysregulation disorder was assessed by psychiatrist. RESULTS: There is a new phenomenon that emotional dysregulation has been frequently noticed in severely gaming-addicted ADHD youth. Treatment efficacy of IGD is good when the underlying symptom of ADHD is controlled. Symptom scores of disruptive mood dysregulation (DMDD) were significantly reduced by 71.9%, 74.8%, and 84.4% at week 2, 3, and 4, respectively (P ≤ .001) after adjusting baseline symptom severity. CONCLUSION: IGD may strongly arouse emotional dysregulation. Future DSM criteria could consider these gaming-addicted youth as a specific subclass of ADHD.

Increased risk of developing psychiatric disorders in children with attention deficit and hyperactivity disorder (ADHD) receiving sensory integration therapy: a population-based cohort study.

Parents of children with attention deficit hyperactivity disorder (ADHD) have been found to prefer sensory integration (SI) training rather than guideline-recommended ADHD treatment. This study investigated whether SI intervention for children with ADHD was associated with a reduced risk of subsequent mental disorders. From children < 8-years-old newly diagnosed with ADHD in a nationwide population-based dataset, we established a SI cohort and a non-SI cohort (N =  1945) matched by propensity score. Incidence and hazard ratios of subsequent psychiatric disorders were compared after a maximum follow-up of 9 years. The incidence of psychiatric disorders was 1.4-fold greater in the SI cohort, with an adjusted hazard ratio of 1.41 (95% confidence interval 1.20-1.67), comparing to the non-SI cohort. Risks were elevated for emotional disturbances, conduct disorders, and adjustment disorders independent of age, gender, or comorbidity. Among children with only psychosocial intervention, the incidence of psychiatric disorders was 3.5-fold greater in the SI cohort than in the non-SI cohort. To our knowledge, this is the first study to report an increased risk of developing psychiatric disorders for children with ADHD who received SI compared to those who did not. Potential adverse effects of SI for ADHD children should be carefully examined and discussed before practice.

Association of depression and loneliness with specific cognitive performance in non-demented elderly males.

BACKGROUND: Loneliness and depression are very common in the aged population. Both have negative impacts on cognition in the elderly. The present study aimed to investigate the effect of loneliness and depression on total as well as specific cognitive domains in cognitively normal male subjects. MATERIAL/METHODS: A total of 189 cognitively normal male subjects were recruited and underwent Cognitive Abilities Screening Instrument (CASI) and Wechsler Digit Span Task tests. Depression was assessed by the Geriatric Depression Scale-Short Form (GDS-SF) and loneliness by UCLA loneliness scales. Partial correlation test was used to explore the correlation between loneliness/depression and total as well as specific cognition function, with the controlled factors of age and education. RESULTS: Both depression and loneliness are negatively correlated with global cognitive function as evaluated with CASI (r=-0.227, p=0.002; r=-0.214, p=0.003, respectively). The domains of Attention, Orientation, Abstraction and judgment, and List-generating fluency of cognitive function were specifically associated with loneliness, and the domain of orientation was associated with depression after controlling the factors age and years of education. CONCLUSIONS: Our findings suggest that loneliness and depression may have negative impacts on global and specific domains of cognitive function in non-demented elderly males. Both loneliness and depression should be actively recognized earlier and appropriately treated because they are significant sources of cognitive impairment in the elderly.

Treatment effects of combining social skill training and parent training in Taiwanese children with attention deficit hyperactivity disorder.

BACKGROUND/PURPOSE: Children with attention-deficit/hyperactivity disorder (ADHD) often have problems in social interactions. We investigated the social and behavioral effects of providing both social skill training and parent training to school-aged children with ADHD in Taiwan. METHODS: Seven consecutive 8-week behavioral-based social skill training (SST) group sessions were held for 48 children with ADHD; parallel 8-week parent group sessions were provided simultaneously. Fifty-five children with ADHD were recruited as a control group. All children took medication as prescribed by their doctors. The effects were assessed using the teacher and parent version of the Chinese version of Swanson, Nolan, and Pelham, version IV scale (SNAP-IV), the Chinese version of the Child Behavior Check List (CBCL-C), child and teacher version of the modified Social Skill Rating System (SSRS-C and SSRS-T), at baseline, post-treatment, and 4 months from baseline. The doses of methylphenidate and drug compliance were controlled during the analysis. RESULTS: The mixed-effects model demonstrated the main effect of group sessions on the Oppositional subscale of SNAP-P, the Anxious/Depressed subscale of CBCL-C, the Self Control subscale of SSRS-C, and the Active Participation subscale of SSRS-T, all in favor of the experimental group. However, the improvement on the Oppositional subscale of SNAP-P and the Self Control subscale of SSRS-C were noted only between baseline and post-treatment period and were not sustained at the end of the follow-up period. CONCLUSION: Our study demonstrated that children with ADHD could benefit from this low intensity psychosocial program, although some improvements were not maintained at follow-up assessment.

Transient childhood psychosis after upper respiratory infection.

Two cases of psychosis after upper respiratory infection were reported. New mental illness among children was substantiated after analyzing the cause of psychosis during the past 10 years of practice. It is confirmed that there is an association between psychosis and upper respiratory infection.

Therapeutic efficacy of probiotics for symptoms of attention-deficit hyperactivity disorder in children and adolescents: meta-analysis.

BACKGROUND: The efficacy of probiotics as a therapeutic alternative for attention-deficit hyperactivity disorder (ADHD) remain unclear. AIMS: To investigate the effectiveness of probiotics for symptoms of ADHD and identify possible factors affecting their efficacy. METHOD: Randomised placebo-controlled trials were identified through searching major databases from inception to April 2023, using the main keywords 'probiotics' and 'ADHD' without limitation on languages or geographic locations. The outcome of interest included improvement in total symptoms of ADHD, symptoms of inattention and hyperactivity/impulsivity, and drop-out rate. Continuous and categorical data were expressed as effect sizes based on standardised mean differences (SMDs) and odds ratios, respectively, with 95% confidence intervals. RESULTS: Meta-analysis of seven trials involving 379 participants (mean age 10.37 years, range 4-18 years) showed no significant improvement in total symptoms of ADHD (SMD = 0.25; P = 0.12), symptoms of inattention (SMD = 0.14; P = 0.3) or hyperactivity/impulsivity (SMD = 0.08; P = 0.54) between the probiotic and placebo groups. Despite non-significance on subgroup analyses, there was a large difference in effect size between studies using probiotics as an adjunct to methylphenidate and those using probiotics as supplementation (SMD = 0.84 v. 0.07; P = 0.16), and a moderate difference in effect size between studies using multiple strains of probiotics and those using single-strain regimens (SMD = 0.45 v. 0.03; P = 0.19). CONCLUSIONS: Current evidence shows no significant difference in therapeutic efficacy between probiotics and placebos for treatment of ADHD symptoms. However, albeit statistically non-significant, higher therapeutic efficacies associated with multiple-strain probiotics or combining probiotics with methylphenidate may provide direction for further research.

Efficacy and tolerability of psychostimulants for symptoms of attention-deficit hyperactivity disorder in preschool children: A systematic review and meta-analysis.

BACKGROUND: There was no previous meta-analysis investigating the efficacy/tolerability of psychostimulants for symptoms of attention-deficit hyperactivity disorder (ADHD) in preschool children. METHODS: Databases including PubMed, the Cochrane Library, EMBASE, ScienceDirect, and ClinicalTrials.gov were searched from inception to March 2022 for randomized controlled trials (RCTs) on therapeutic efficacy of psychostimulants against ADHD symptoms in preschool children (age ≤6 years) compared with placebos. Primary outcomes were (a) changes in ADHD symptoms evaluated by validated rating scales from parents'/teacher's observation, or (b) post-intervention improvements in neuropsychological performance. Secondary outcomes were risks of adverse events. RESULTS: Meta-analysis of nine eligible trials including 544 preschool children (mean age=4.86 years, female=11.98%, median treatment duration=4.33 weeks) supported the efficacy of psychostimulants against global symptoms from observations of parents (Hedges' g=0.6152, p<0.0001) and teachers (Hedges' g=0.6563, p=0.0039). Efficacy of psychostimulants was also noted against symptoms of inattention and hyperactivity/impulsivity, especially the latter (i.e., main symptoms in preschool children). Moreover, male gender, older age, and longer treatment duration were associated with better efficacy. Regarding adverse events, only the risk of poor appetite was higher in the psychostimulant group (odds ratio [OR]=2.39). However, the qualities of evidence were low to very low, indicating potential discrepancy between the true and estimated effect. CONCLUSIONS: Our results showed that psychostimulants might be beneficial for preschool children with ADHD, especially hyperactivity/impulsivity from teachers' observation, with tolerable side effects. Nevertheless, the true magnitude of the effect needs to be confirmed with more research due to low to very low certainty of the evidence.

Efficacy of electrical cranial stimulation for treatment of psychiatric symptoms in patients with anxiety: A systematic review and meta-analysis.

Background: Therapeutic effects of electrical cranial stimulation (CES) in patients suffering from anxiety remained unclear. This meta-analysis aimed at investigating acceptability and therapeutic efficacy of CES against anxiety, depression, and insomnia for patients who experienced symptoms of anxiety. Methods: Major electronic databases were searched from inception until December 10, 2022 for randomized controlled trials (RCT) focusing on therapeutic effectiveness of CES in patients whose primary complaints included anxiety. Effect sizes (ES) for different treatment outcomes were estimated by using generic inverse variance method. Results: Eight RCTs were identified including a total of 337 participants. The therapeutic effectiveness of CES was significantly better than that in the control groups for anxiety (ES=-0.96, p <0.00001, eight trials, 337 patients), depression (ES=-0.69, p=0.003, five trials), and insomnia (ES=-1.02, p = 0.0006, three trials) in those who presented with symptoms of anxiety. Subgroup analyses found that CES was equally effective regardless of comorbid presentation of depressive symptoms (ES=-0.94 in patients with anxiety only vs. ES=-1.06 in those with depression and anxiety) and whether CES was used as monotherapy or add-on therapy to medications (ES = -0.88 vs. ES = -1.12, respectively). Moreover, subgroup analysis of RCTs using the same device "Alpha-Stim" for CES was more effective in alleviating anxiety than sham controls (ES = -0.88, p < 0.00001, four trials, 230 patients). Regarding acceptability, the use of CES did not increase the risk of treatment-related dropout compared to the control group (RR = 1.26, p = 0.57, I2 = 0%, four trials, 324 patients). Conclusion: Our study supported the use of CES for symptoms of anxiety, depression, and insomnia in those suffering from anxiety with fair acceptability and demonstrated the efficacy of "Alpha-Stim", the most commonly used device for CES, in this patient population. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022382619.

Psychosocial stress in children with Tourette syndrome and chronic tic disorder.

BACKGROUND: This study aimed to understand the longitudinal relationship between psychosocial stress with tic exacerbation in children with Tourette syndrome (TS) and chronic tic disorder. METHODS: Consecutive ratings of tic severity as well as child and parental reports of psychosocial stress were obtained for 373 children (296 males, 77 females; mean age 9y 5mo; SD 3y 3mo) with TS and chronic tic disorder between January 2018 and December 2020. The Yale Global Tic Severity Scale (YGTSS) global severity score, total tic score, and impairment rating were calculated. The stressful events and YGTSS measurements were used and treated as time-varying variables in the analyses. Models that controlled for non-independence among the repeated observations using a random intercept and random slope model were employed. Each participant was treated as a random factor in the modelling. RESULTS: Family-related stress, personal relationship stress and school-related stress were independently associated with increasing YGTSS global severity, total tic score, and impairment rating over time. An increased number of stressful events were associated with increased severity of tics. CONCLUSION: Family, personal relationships, and school-related stress were consistently associated with the exacerbation of tics. Managing these stressful events is important in the treatment of TS and chronic tic disorder.

Effects of probiotics on neurocognitive outcomes in infants and young children: a meta-analysis.

Background: Therapeutic efficacies of probiotics in improving neurocognitive functions in infants and young children remained unclear. This meta-analysis focused on different cognitive outcomes in this population. Methods: Major databases were searched electronically from inception to October 2023 to identify randomized controlled trials (RCTs) that investigated the therapeutic efficacy of probiotics in enhancing cognitive functions assessed by standardized tasks. The overall effect size was calculated as standardized mean difference (SMD) based on a random effects model. Results: Nine RCTs with 3,026 participants were identified. Both our primary and secondary results demonstrated no significant difference in neurocognitive outcomes between infants/children treated with probiotics and those receiving placebos. However, our subgroup analysis of studies that offered a probiotics treatment course of over six months demonstrated a significantly better neurocognitive outcome than placebos (SMD = 0.21, p = 0.03, two studies with 451 participants), but this finding was based on only two RCTs. Conclusion: Despite lack of significant therapeutic effects of probiotics on neurocognitive outcomes, our finding of a positive impact of probiotics on neurocognitive development in those undergoing treatment for over six months may provide an important direction for further investigations into the enhancement of therapeutic effects of probiotics on neurocognitive development in infants and young children. Systematic review registration: PROSPERO CRD42023463412.

Naturalistic exploration of the effect of osmotic release oral system-methylphenidate on remission rate and functional improvement in Taiwanese children with attention-deficit-hyperactivity disorder.

AIM: To determine the differences in the remission rate, recovery rate, functional improvement, and treatment adherence related to treatment with short-acting immediate-release methylphenidate (IR-MPH) and long-acting osmotic-release oral system-methylphenidate (OROS-MPH) in a naturalistic setting among Taiwanese children with attention-deficit-hyperactivity disorder (ADHD). METHODS: A total of 757 children with ADHD, aged 6-18 years, was evaluated using the following in order determine functional improvement and treatment adherence: the Chinese version of the Swanson, Nolan, and Pelham, version IV scale (SNAP-IV-C), Clinical Global Impression-ADHD-Severity (CGI-S) to measure remission and recovery rates, the Chinese version of the Social Adjustment Inventory for Children and Adolescents (CSAICA), and caregiver's satisfaction rate, treatment adherence, and frequency of adverse effects. RESULTS: According to the SNAP-IV-C scores, the remission rate was 30.72%, and the recovery rate was 16.38%. Compared to short-acting IR-MPH, OROS-MPH was associated with greater functional improvement and treatment adherence among children with ADHD. CONCLUSION: OROS-MPH treatment at the adequate dosage can achieve higher remission and recovery rates, produce greater functional improvement, and result in better treatment adherence than IR-MPH treatment.

Generalized structural equation modeling: Symptom heterogeneity in attention-deficit/hyperactivity disorder leading to poor treatment efficacy.

BACKGROUND: Treatment efficacy for attention-deficit/hyperactivity disorder (ADHD) is reported to be poor, possibly due to heterogeneity of ADHD symptoms. Little is known about poor treatment efficacy owing to ADHD heterogeneity. AIM: To use generalized structural equation modeling (GSEM) to show how the heterogeneous nature of hyperactivity/impulsivity (H/I) symptoms in ADHD, irritable oppositional defiant disorder (ODD), and the presentation of aggression in children interferes with treatment responses in ADHD. METHODS: A total of 231 children and adolescents completed ADHD inattention and H/I tests. ODD scores from the Swanson, Nolan, and Pelham, version IV scale were obtained. The child behavior checklist (CBCL) and parent's satisfaction questionnaire were completed. The relationships were analyzed by GSEM. RESULTS: GSEM revealed that the chance of ADHD remission was lower in children with a combination of H/I symptoms of ADHD, ODD symptoms, and childhood aggressive behavior. ODD directly mediated ADHD symptom severity. The chance of reaching remission based on H/I symptoms of ADHD was reduced by 13.494% [= exp (2.602)] in children with comorbid ADHD and ODD [odds ratio (OR) = 2.602, 95% confidence interval (CI): 1.832-3.373, P = 0.000] after adjusting for the effects of other factors. Childhood aggression mediated ODD symptom severity. The chance of reaching remission based on ODD symptoms was lowered by 11.000% [= 1 - exp (-0.117)] in children with more severe baseline symptoms of aggression based on the CBCL score at study entry [OR = -0.117, 95%CI: (-0.190)-(-0.044), P = 0.002]. CONCLUSION: Mediation through ODD symptoms and aggression may influence treatment effects in ADHD after adjusting for the effects of baseline ADHD symptom severity. More attention could be directed to the early recognition of risks leading to ineffective ADHD treatment, e.g., symptoms of ODD and the presentation of aggressive or delinquent behaviors and thought problems in children with ADHD.

Structural Equation Modeling (SEM): Gaming Disorder Leading Untreated Attention-Deficit/Hyperactivity Disorder to Disruptive Mood Dysregulation.

(1) Background: Internet gaming disorder (IGD) in youths likely leads to disruptive mood dysregulation, especially among those with attention-deficit/hyperactivity disorder (ADHD). Whether IGD mediates the pathways leading ADHD to disruptive emotional dysfunction remains unclear. This study aims to elucidate the direct or indirect influence of IGD on ADHD; (2) Method: The Swanson, Nolan, and Pelham Version IV questionnaire was used to evaluate symptoms of ADHD and oppositional defiant disorder, and the Chen gaming disorder scale was used to measure IGD. A psychiatrist diagnosed ADHD, IGD, and disruptive mood dysregulation disorder (DMDD)-like symptoms. Structural equation modeling was applied to evaluate the role of IGD in mediating ADHD progression to disruptive mood dysregulation; (3) Results: Among a total of 102 ADHD youths, 53 (52%) of them with IGD were significantly more likely to have poor interpersonal relationships (p < 0.01) and DMDD-like symptoms (p < 0.01) than ADHD youths without IGD. IGD played a mediating role in increasing the risk of disruptive mood dysregulation in ADHD youths; (4) Conclusions: The findings suggest that IGD mediates ADHD's progression to disruptive mood dysregulation. Intensive biopsychosocial interventions are warranted for ADHD youths with IGD. More children and adolescents became mood-dysregulated after excessive gaming during the COVID-19 pandemic; this study's results suggest that child mental health experts develop earlier detection and prevention strategies for children and adolescents hidden behind internet addiction.

The Comparative Efficacy of Treatments for Children and Young Adults with Internet Addiction/Internet Gaming Disorder: An Updated Meta-Analysis.

Internet gaming disorder (IGD) is a formal mental disorder leading to bad outcomes for children and adolescents. This study comprehensively compared the estimated effect of various pharmacotherapy and psychosocial interventions for IGD from randomized controlled trials (RCT) through updated meta-analysis, using meta-regression. A search of PubMed/MEDLINE, Cochrane Library, and Airiti Library between 2000 and 2017 was conducted for various IA/IGD intervention modalities. A total of 124 studies from 29 selected papers involving 5601 children and young adults with IA/IGD were found. Meta-analyzing the pooled standardized mean difference (SMD) revealed a preliminary random effect of 1.399 with a 95% confidence interval of 1.272-1.527, suggesting highly effective treatment of IA/IGD. After adjusting for the confounding risks of age, publication year, type of subjects, and type of study, this study revealed that combining pharmacotherapy with cognitive behavioral therapy (CBT) or multi-level counseling (MLC) was the most effective treatment option. Using a scale of time spent online or a severity of IA symptoms scale was a more effective measurement, with p-values = 0.006 and 0.002, respectively. IA/IGD patients with comorbid depression showed worse outcomes than youth with another comorbidity. The corresponding model goodness-of-fit indices were τ2 = 1.188; I2-Residual = 89.74%; and Adjusted-R2 = 16.10%. This systematic review indicates that pharmacotherapy combined with CBT or MLC might be an effective therapeutic strategy for youth with gaming disorder.