. 2022 Nov 29;13:986687. doi: 10.3389/fpsyt.2022.986687

Table 2.

The summary of 21 studies that examined the therapeutic effects of DTx for children and adolescents.

Study & DTx	Participants	Measures	Follow-up	Results	Limitations
Anguera et al. (60) EndeavorRx	1. Children with SPD + IA (N_Experiment1 = 20, N_female = 8, M_age = 9.7 ± 1.3; N_Experiment2 = 20, N_finalsample = 17). 2. Age- and gender-matched children with SPD (N_Experiment1 = 17, N_female = 8; M_age = 10.3 ± 1.5; N_Experiment2 = 13, N_finalsample = 10). 3. Typically developing children (N_Experiment1 = 25, N_female = 12, M_age = 10.5 ± 1.3; N_Experiment2 = 24, N_finalsample = 22).	Behavioral measures - Perceptual discrimination paradigm - TOVA - EVO assessment (i.e., perceptual discrimination, visuomotor tracking and multitasking ability) - Parent report measure Vanderbilt ADHD Diagnostic Parent Rating Scale Neural assessment - EEG Additional measure for confounding variables - Basic response time task	9 months	Behavioral changes in cognitive control - Improved performance in the perceptual discrimination in children with SPD+IA and typically developing children - Improved performance in the TOVA in all groups - Improved reaction time in EVO assessments in all groups - No group difference in basic response time task Parent report of attention - Significantly reduced inattention behaviors in children with SPD+IA after the training and at 9-month follow-up Neural assessment - Significantly increased MFT power in children with SPD+IA - A correlation between the improvement of MFT power and decreased parental reports of inattentive behaviors	- The lack of power for the dissociation of attention-based improvements on behavioral measures - The lack of SPD placebo control group
Davis et al. (42) EndeavorRx	Children who were aged between 8–12 years and whose functioning was within the normal range of intellectual functioning	Safety and feasibility measures - Parental reports of adverse events - Compliance	No follow-up	Safety and feasibility - The completion of 84% of prescribed in-home sessions across all participants - Reports of 9 adverse events that were not related to EVO over all study phases	- The necessity of additional measures for the translation of cognitive improvement to everyday functioning - The plausible influence of parent expectations for the intervention treatment effects on the observed
	1. Children with ADHD (N = 40, N_female = 16; M_age = 10.3 ± 1.2) 1–2. ADHD high severity subgroup(N = 22, N_female = 8; M_age = 10.2 ± 1.2) 2. Age-matched typically developing children (N = 44, N_female = 19, M_age = 10.5 ± 1.4; N_finalsample = 40)	- Questionnaire on intervention appeal Measures for attention and other cognitive functions - TOVA - BRIEF–Parent Form CANTAB		-6.9 of enjoyment rating for EVO on a 1-10 scale Attention functioning - Significantly improved performance in API of the TOVA in children with ADHD and a greater intervention effect in ADHD high severity subgroup - Significant improvements on indicators of ADHD severity (i.e., Reaction Time Mean Standard Score and Reaction Time Variability Standard Score) only in the ADHD high severity subgroup Cognitive functioning - Improved spatial WM in children with ADHD and the improvement in rapid visual processing and delayed match to sample in typically developing children - Non-significant improvement of WM in children with ADHD and the significant improvement of WM and inhibition in the ADHD high severity subgroup - No changes in summary scores of BRIEF (i.e., metacognition, behavioral regulation, global executive composite) over time in all groups	improvement in parent reports - The limited generalizability of the findings to the entire general population of children with ADHD - Concern for Type 1 error for some results despite the Bonferroni correction for significant values
Yerys et al. (57) EndeavorRx	Children with ASD and ADHD (N_screened = 42, age range = 9–15 years;	Measures of attention and cognitive functions	No follow-up	Feasibility and acceptability	-The use of control treatment condition that completely differed from the experimental condition
	N_eligible = 19, N_female = 2, age range = 9–13 years, M_age = 11.25 ± 1.44) 1. Multi-tasking treatment group (N = 11) 2. Alternative educational treatment group (N = 8)	Primary outcome measure: TOVA - ADHD-RS-IV: Home - BRIEF, 2^nd edition - CANTAB - SSIS		-A high level of adherence to the treatment protocol in both groups and no withdrawal of children from the study - Positive reports for the benefits of the intervention in both children and adolescents Preliminary Efficacy - Non-significant but improved performance in the TOVA API in the multi-tasking treatment group and non-significant but overall worsening in the TOVA API in the alternative educational treatment group - Significant reductions in ADHD-RS-IV, BRIEF-2, SSIS problem behaviors in the multi-tasking treatment group but non-significant reductions in ADHD-RS-IV, BRIEF-2 and SSIS problem behavior scores in the alternative educational group - No significant gains in CANTAB's spatial WM and SSIS Social skills in both groups	-The plausible influence of parent perception of engagement on the parent ratings that were conducted after the treatment - The exclusion of a large percentage of children with ADHD at the screening stage - Some concerns of the extent to which TOVA measures cognitive interference
Kollins et al. (44) EndeavorRx	Children with ADHD (N_screened = 857, N_eligible = 348, age range: 8–12 years)	Primary outcome measure - The mean change in TOVA Secondary outcome measure	No follow-up	Feasibility - No parent reports of serious adverse events related to the intervention but some reports of frustration (3%) and headache (2%) in AKL-T01 group	-The exclusion of a substantial number of children with ADHD due to the criteria for attention deficit - The limited generalizability of findings to the broader populations of children with ADHD with comorbid condition or taking medication for ADHD
	1. AKL-T01 group (N = 180, N_female = 55, age = 9.7 ± 1.3; N_finalsample = 169) 2. Control group (N = 168, N_female = 45, age = 9.6 ± 1.3; N_finalsample = 160)	-IRS - ADHD-RS-IV - CGI-I - BRIEF		-No dropout in both groups due to adverse events Primary outcome - Significant improvement in TOVA API score in AKL-T01 group but not in control group - The greater improvement in the TOVA API in the AKL-T01 G compared to the control group with the movement of more children with ADHD into the normative ranges of attention functioning after the intervention Secondary outcomes - Significant improvement in all secondary measures but no group differences in secondary measures (i.e., IRS, ADHD-RS, ADHD-RS-I, ADHD-RS-H, BRIEF-Parent Inhibit and Working Memory and Metacognition) - Significantly higher parental-reported improvement of attention in the AKL-T01 G - Significant effects on ADHD-RS, ADHD-RS-I and CGI-I in children who discontinued stimulant medication for AKL-T01 intervention	-Concerns for the beneficial effects of the intervention on attention in different intervention periods or after the intervention period - No power calculations for secondary outcomes or post-hoc analyses - No collection of mechanistic data (e.g., EEG)
Gallen et al. (71) EndeavorRx	28 children with ADHD (N_finalsample = 25,	Primary measure	No follow-up	Neural assessment outcome	-No placebo control group for the comparison
	N_male = 20, M_{age =} 10.44 ± 1.23, age range: 8–12)	-Neural assessment: EEG recording during a perceptual discrimination task (i.e., go/no-go task) Behavioral measures - Perceptual discrimination task - Sustained attention task (i.e., visual continuous performance task) Parent-report measure - Vanderbilt ADHD diagnostic parent scale		-Increased MFT activities at the early and later stages of a go/no-go task but non-significant increases in MFT activities in the peak time of the task Behavioral assessment outcomes - Significantly improved reaction time in perceptual discrimination task after the intervention - No improvement in reaction time or reaction time variability in sustained attention task but the improvement in attention lapses - No relation of basic response time changes with intervention-related improvements in behavioral outcomes Parent-reports - Significant decreases in parent-reported ADHD inattention symptoms Relationship between neural and behavioral assessments - A significant relation of MFT-changes in early and post stages with the improvement of attention lapses in the sustained attention task	-Concerns for the persistency of the neural effects and the uncertainty in the relationship of the neural effects with aforementioned behavioral measures for attention - No correction for multiple comparisons in the reported association between neural and behavioral gains - The necessity of the replication of a lager sample of the heterogeneous ADHD population
Lim et al. (4) ATENTIVmynd	Children who were diagnosed to have	Neural measure	3 months with three once-monthly booster training sessions	Adherence	-The possibility of the exaggeration of the treatment effect due to uncontrolled open-label design of the study
	ADHD without the experience of stimulant medication treatment (N_enrolled = 25; N_eligible = 20, N_female = 4, age range: 6–12 years, M_age = 7.8 ± 1.4). - children with the combined subtype of ADHD (N = 14). - children with inattentive subtype of ADHD (N = 6).	- BASM Outcome measure - ADHD-RS completed by parents		- The completion of the study in 85% participants (N=17) Neural outcome - Non-significant but increasing trend in the mean BASM scores (i.e., the improvement of inattentive symptoms) in Week 20 (i.e., the post-boosters period) compared to in Week 0 (i.e., baseline) Behavioral outcomes Significant decreases in inattentive symptoms, hyperactive impulsive and combined symptoms immediately after the intervention - No significant further improvement in inattentive or hyperactive-impulsive symptoms of ADHD by receiving monthly booster trainings for 3 consecutive months after the intervention but sustained intervention effect at 24 weeks - Greater improvements in attention in children with more severe inattentive, hyperactive-impulsive and combined symptoms immediately after the intervention
Qian et al. (72) ATENTIVmynd	Boys with ADHD (either combined or inattentive subtypes)	Neuropsychological measures	No follow-up	Neuropsychological outcomes	-A relatively small sample size after removing poor-quality data that resulted from the excessive motion
	1. Intervention group (N = 44, N_finalsample = 18, M_age = 9.00± 1.50) 2. Control group (N = 22, N_finalsample = 11, M_age = 9.45± 1.29)	-ADHD-RS - CBCL Neural measure - rs-fMRI and structural MRI		- Significantly greater reduction in inattention scores of the ADHD-RS in the intervention group compared to the control group - Non-significant but slightly greater reduction in CBCL internalizing problems in the intervention group than in the control group Neural outcome - A trend of increased functional connectivity within and between relevant networks (e.g., salience/ventral attention network, dorsal attention networks) only in control group over time - Significant reductions in nodal degree and clustering coefficient but significantly increased nodal closeness in salience/ventral attention network, executive control network and default mode network after the intervention - The correlation of changes in functional networks (i.e., less increased functional connectivity in the intra-salience/ventral attention network and the inter-network between salience/ventral and dorsal attention networks and reduced local functional processing in relevant brain regions) after the intervention with the	-The possibility of further correction of physiological noise in the fMRI dataset through the implementation of advanced fMRI preprocessing techniques ADHD subtypes that were not distinguished due to relatively small sample size - The necessity of further studies with a longer duration of the intervention and follow-ups
				improved inattention symptom and internalizing problems in children with ADHD
McDermott et al. (20) ATENTIVmynd	46 children with ADHD (N_female = 14; age range = 8–12 years, M_age = 9.57 ± 1.34) 1. Intervention group (N = 21) 2. Waitlist group (N = 19) *Children who dropped during the training or wait period (N = 6)	Behavioral measures - ADHD-RS completed by clinicians - CGI-I - Quotient^® ADHD system Academic measures - PERMP - WJ-III	3 months	Behavioral outcomes - Significant decreases in both ADHD-RS mean scores and mean score of CGI in the intervention group - Worsening performances of the intervention group in Quotient^® ADHD system which was found to be not correlated with behavioral reports or training-related improvements - The maintenance of intervention-related improvements at the follow-up Academic outcomes - Significantly improved performance in the PERMP in the intervention group compared to waitlist group - A trend of improved performance in WJ-III understanding directions (i.e., the ability to control their impulses and follow directions) in the intervention group but no group differences in Reading fluency and Math fluency	-Potential expectation bias of clinicians and parents on the intervention effect due to non-blind group assignment - No comparison of the intervention against one evidence-based treatment due to various options of treatments, including no treatment, that were given to the control group - No comparison group at the follow-up - Limited generalizability of the findings due to relatively small sample size
García-Baos et al. (63) RECOGNeyes	28 Children and adolescents with ADHD (including 7 children with comorbid dyslexia and 2 children with a	Acceptability measure - A usability and enjoyability questionnaire	No follow-up	Acceptability outcome - Reports of appropriateness of difficulty level and enjoyment in the majority of children who were younger than 12 years	- Some group differences in the number and duration of fixations in the short word task at the baseline - The necessity for a longer period of intervention with a larger sample size
	learning disability; N_boy = 18, age range: 8–15 years) 1. RECOGNeyes group 2. Age-matched control group using mouse to play the game	Behavioral measures - frog task (i.e., probability of ADHD, severity of ADHD, hyperactivity index, impulsivity index) - word recognition task (i.e., dyslexia index, performance parameters)		Behavioral outcomes - Significantly decreased impulsivity score in the RECOGNeyes group after the intervention - Significantly decreased reaction time for attention, increased durations of fixations and decreased number of fixations in attention assessment tasks in the RECOGNeyes group after the intervention
David et al. (11) REThink	Children and adolescents (N = 165, N_finalsample = 142, N_female = 91; age range: 10–16 years) 1. REThink group (N = 48; M_age = 13.0 ± 2.0) 2. REBE group (N = 48; M_age = 12.7 ± 1.9) 3. Waitlist group (N = 46; M_age = 12.9 ± 2.2)	Acceptability measure - TS-VAS Primary measures - SDQ—child version - The subscale of depressive moods from EATQ-R Secondary measures - ERICA - Other three subscales (i.e., attention, fear, inhibitory control) of EATQ-R - FD-CMS—girls and boys versions	No follow-up	Acceptability outcome - Significant difference in satisfaction between REThink and REBE group in the middle of the intervention but no-significant group difference in the satisfaction after the intervention Primary outcomes - Significantly decreased scores of SDQ emotional symptoms and EATQ-R depressive mood Secondary outcomes - Significantly increased ERICA awareness in the REThink group - Significantly increased scores of EATQ-R attention and ERICA control in the REThink group and the REBE group - Marginally significant group difference in SDQ peer-relationship problems	The possibility of the lack of significant results for REBE intervention due to the delivery of the intervention in schools - The necessity for the follow-up - Validation issues of some measures (e.g., FD-CMS)
David et al. (73) REThink	Children and adolescents (N = 165, N_finalsample = 142, N_female = 91; age range: 10–16 years) 1. REThink group (N = 48, N_female = 36; M_age = 13.0 ± 2.0) 2. REBE group (N = 48, N_female = 31; M_age = 12.7 ±1.9) 3. Waitlist group (N = 46, N_female = 22; M_age = 13.0 ± 2.2)	Primary measures - SDQ—child version - EATQ-R Measures for hypothesized mediating variables - CASI - CATS-N/P	No follow-up	- No change in CASI total score in the waitlist group and marginal, non-significant change in CASI total score in the REBE group but significantly decreased CASI total score in the REThink group -The significant association of changes in CASI total score with SDQ emotional symptoms and EATQ-R depressive symptoms in the REThink group -The prediction of group contrast (i.e., the REThink group or the waitlist group) for changes in CASI total scores, SDQ emotional symptoms and EATQ-R depressive mood -No difference in the intervention efficacy depending on the age or gender	- The usage of standard assessment points -The delivery of interventions in schools and children's previous exposure to such intervention programs
David et al. (24) REThink	Children and adolescents (N = 165, N_finalsample = 134; age range: 10–15 years) REThink G (N = 47, N_female = 34; M_age = 13.04 ± 2.07) REBE G (N = 42, N_female = 23; M_age = 12.81 ± 1.92) Waitlist G (N = 45, N_female = 21; M_age = 12.96 ± 2.17)	Report measures -‘concern and anxiety' subscale of PAD Neural measures - EEG data of frontal brain regions during the impromptu speech task	No follow-up	Report outcome - Significant decreases in state anxiety in all groups after the intervention Neural outcome - Increased frontal alpha asymmetry scores in the REThink group after the intervention - Significant negative relationship between frontal alpha asymmetry and state anxiety after the REThink intervention	- The limited generalizability of this findings based on a convenience sample - The dropout of participants that resulted from the inherent limitation of the used equipment - No validation of the anxiety subscale of the PAD in children and adolescent samples - The lack of control on the metacogntion for children and adolescents in the subjective measure
Ducharme et al. (66) Mightier	Children and adolescents who did not show the improvement in the anger control with treatment as usual (age range: 9–17 years) 1. Intervention group that had received anger control therapy with mightier (N = 20, N_finalsample = 18, N_female = 13; M_age = 13.7 ± 2.1) 2. Treatment as usual group that had received anger control therapy (N = 19, N_female = 9; M_age = 14.7 ± 2.4)	Acceptability measure - The therapeutic helpfulness questionnaire Behavioral measure - STAXI-CA Physiological measure - Heart Rate - The therapeutic helpfulness questionnaire	No follow-up	Acceptability outcome - A high level of satisfaction and helpfulness with the treatment in the intervention group Behavioral outcome - Significantly decreased scores of STAXI-CA subscales (i.e., state anger, trait anger and anger expression-out) and marginally decreased scores of anger expression-in subscale in the intervention group Physiological outcome - Significantly improved ability to maintain their heart rate in the intervention group	- The small sample size - The use of not a randomized control but a historic control group and the lack of cultural diversity of the experimental group - No inclusion of objective measures for anger or aggression
Ducharme et al. (74) Mightier	One 16-years-old girl who disclosed depression, suicidal ideation and thoughts of hurting family members	Acceptability measure - Revised session reaction scale Behavioral measure - STAXI-CA	No follow-up	Acceptability outcome - Positive feedback on the intervention experience (e.g., enjoyment, helpfulness) Behavioral/Report outcomes - Decreased scores of State Anger and Trait Anger after the intervention - Considerable improvement in the ability to use emotional regulation skills and to control heart rate after the intervention	-Engagement issues of patients with anger problems in the intervention - Difficulty to determine the mechanisms that led to the intervention-related improvement - Unknown generalizability of the improvement to the contexts outside the therapeutic settings - The necessity of randomized clinical trials - Plausible constraints (e.g., the necessity of managed care for more than five consecutive days) on the benefits of the intervention
Schoneveld et al. (37) MindLight	Children showing elevated anxiety symptoms (N_screened = 757, N_finalsample = 136, N_female = 73; age range: 8–13 years, M_age = 9.95 ± 1.33) 1. MindLight group (N = 9, N_dropout = 1) 2. Control game (i.e., “Max”) group (N = 67, N_dropout = 1)	Acceptability and feasibility measures - Game expectations - Game evaluations Behavioral measures - SCAS-C/P Additional measure - Average weekly time for game playing	3 months	Acceptability and feasibility outcomes - No group difference in game expectations at the baseline - The evaluation of MindLight as a significantly more anxiety-inducing game compared to Max and the evaluation of Max as a significantly more appealing game compared to MindLight Behavioral outcomes - Significantly lower mean scores on total anxiety symptoms in the MindLight group than in the control game group at the post-test but non-significant effect of game conditions on anxiety outcome measures - No group difference in anxiety symptoms at the follow-up; significant decreases in levels of anxiety symptoms in both groups over time	-The potential bias in report measurements - The possibility of the contamination between the groups due to the play context where both groups played in the same room - The exclusion of a passive control group - The lack of the understanding about reasons for the improvement in children's anxiety symptoms
Schoneveld et al. (76) MindLight	Children showing elevated anxiety symptoms (N = 174, N_female = 103; age range: 7–12 years, M_age = 9.97 ±1.16) 1. MindLight group (N = 86, N_finalsample = 72) 2. CBT group (N = 88, N_finalsample = 72)	Acceptability and feasibility measures - Program expectations before the group allocation - The evaluation of the program the participants received Behavioral measures - SCAS-C/P Additional measure - Average weekly time for game playing	3 months and 6 months	Acceptability and feasibility outcomes - The children's ratings of MindLight and the CBT program as equally appealing interventions across time points - The rating of the CBT program as more relevant to daily lives than MindLight Behavioral outcomes - Significant decreases in anxiety symptoms over time and slowed rate of the decrease over time - No sigfnicant group difference in anxiety symptoms after the intervention and at follow-ups	- The plausible influence of the information that was given to children and parents to equalize expectations across the conditions on the results - No available information about the mechanisms of the effectiveness of the interventions
Wijnhoven et al. (77) MindLight	Children and adolescents with ASD who showed at least subclinical level of anxiety symptoms (N = 109; age range: 8–16 years, M_age = 11.10 ± 2.07) 1. MindLight group (N = 53) 2. Control game (i.e., “Triple Town”) group (N = 56)	Acceptability measure - PETS Primary outcome measure - SCAS-C Secondary outcome measures - SCAS-P - ADIS-P	3 months	Primary outcome - No significant group differences in child-rated anxiety symptoms after the intervention Secondary outcomes - No significant group difference in parent-rated anxiety symptoms after the intervention but significantly decreased parent-rated anxiety symptoms in the MindLight group compared to the control game group at the follow-up - No group difference in remission rates	- Some concerns for drop-outs and late completion of assessments - The weak original model fits due to the sample size despite the correction - No available information for mechanisms that contributed to the improvement of anxiety symptoms - Some concerns for the reliability of SCAS-C in children with ASD - The interference of the research team in the content of treatments that children received in parallel with MindLight or the control game, and the plausible effects of the treatment contents on anxiety symptoms
					- The usage of ADIS-P as the measurement for the remission rates of anxiety disorders but not as an indicator for changes in anxiety severity
Wijnhoven et al. (78) MindLight	Children with ASD who showed at least subclinical level of anxiety symptoms (N = 8, N_female = 1; Age range: 8–12 years)	- Primary outcome measure - SCAS-C Secondary outcome measures - SCAS-P - ADIS-P - CSLK	3 months	Primary outcome - Clinically significantly decreased anxiety symptoms in five participants during the MindLight intervention Secondary outcomes - Remission of some phobias (e.g., social phobia) and/or generalized anxiety disorder in five children at the follow-up compared to the baseline - Significantly decreased avoidance in three children for more than one phases of the study - Significantly increased positive coping skills (e.g., direct problem solving) in three children, mixed changes in positive coping skills in two children and significantly decreased positive coping skills in one children	- The difficulty to find a significant additive effect of CBT due to the improvement of anxiety symptoms in some children during MindLight sessions - The plausible subjectivity in the visual analysis of data
Merry et al. (58) SPARX	Children and adolescents with mild to moderate depressive disorder (N_screened = 213, N_finalsample = 187; age range: 12–19 years)	Primary outcome measure	3 months	Acceptability and feasibility - Low dropout rates in both groups - A good level of adherence in SPARX group with the completion of at least four modules of SPARX in 86% participants	-The insufficient power of the study to detect the superiority of SPARX over treatment as usual
	1. SPARX group (N = 94, N_dropout = 9, N_female = 59; M_age = 15.55 ± 1.54) 2. Treatment as usual group (N = 93, N_dropout = 8, N_female = 64; M_age = 15.58 ± 1.66)	-CDRS-R Secondary outcome measures - Reynolds adolescent depression scale-second edition - mood and feelings questionnaire - pediatric quality of life enjoyment and satisfaction questionnaire - Spence children's anxiety scale - Kazdin hopelessness scale for children 1. CGI		- The report of 49 adverse events overall but mostly unrelated to the study - The report of helpfulness and satisfaction regarding the interventions in the majority of both groups Primary outcomes - Non-significant but greater reduction in mean scores of CDRS-R in the SPARX group compared to the treatment as usual group - Significantly higher remission rates on the primary outcome in SPARX group than in treatment as usual group Secondary outcomes - Significantly higher changes in mean scores of measures (i.e., Kazdin hopelessness scale, mood and feelings questionnaire and the Spence generalized subscale) in the SPARX group compared to the treatment as usual group but no group difference in the clinical global impression-improvement response rate - Maintained treatment effects in SPARX G at 3-month follow-up	- Logistic difficulty of adding more than one measure on the interview due to various issues (e.g., the necessity of extra time) - No exclusion of spontaneous improvements in both group due to the study design - The heterogeneity of the treatment as usual group
Fleming et al. (79) SPARX	Adolescents with depressive symptoms in alternative schooling	Primary outcome measure	10 weeks	Acceptability outcome	Small sample size - Short follow-up period
	programs (N_screened = 49,N_finalsample = 32; age range: 13–16 years, M_age = 14.9 ± 0.79) 1. SPARX group (N = 20) 2. Waitlist group (N = 12)	- CDRS-R Secondary outcome measures - Reynold Adolescents Depression Scale - Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire - Spence Anxiety Scale - Kazdin Hopelessness Scale - Children's Nowicki-Strickland Internal-External Control Scale short form		-Report of six adverse events (i.e., increased depressive symptoms in four participants in the waitlist group and two self-harm incidents unrelated to the intervention) Primary outcome - Significantly greater decreases in scores of CDRS in the SPARX group than in waitlist group immediately after the intervention - Non-significant changes in outcomes between post-intervention and 10-week follow-up in the SPARX group Secondary outcomes - Significantly greater decreases in Reynold adolescents depression scale in the SPARX group compared to the waitlist group immediately after the intervention but non-significant changes in other secondary outcomes	- Post-intervention and follow-up assessments conducted by the researcher who was not blinded - No validation of used outcome measures in this specific group
Poppelaars et al. (8) SPARX	Girls with elevated depressive symptoms (N = 208; age range: 11–16 years, M_age = 13.35 ± 0.71) 1. OVK (i.e., a depression prevention program) group (N = 50) 2. SPARX group (N = 51)	Acceptability measure - Evaluation of the program at post-test Outcome measures - Reynolds adolescent Depression Scale - Item 9 (i.e., suicidal ideation) of CDI	3-, 6-, and 12-month	Acceptability outcome -Similar level of satisfaction in OVK and SPARX programs - The rating of OVK as a more attractive and useful intervention than SPARX Outcomes - Significant decreases in depressive symptoms over time from the screening to the follow-up in all groups	-The limited genralizability of the findings and the limited random allocation of participants into each group - Small sample size for subgroups of adolescents to be distinguished for the identification of a more effective program - The exclusion of male adolescents by focusing on female adolescents who were at higher risk for depression
	3. OVK and SPARX combined group (N = 56) 4. Monitoring control group (N = 51)			Similar rates of changes in depressive symptoms in all groups and similar level of depressive were at higher risk for depression symptoms in all groups at one-year follow-up - The prediction of greater depressive symptoms at the one-year follow-up from greater depressive symptoms at the baseline - No group difference in suicidal ideation	-Unknown mechanisms for the changes resulted from the intervention - Lack of understanding about the effectiveness of each aspect of games in the context of interventions - The deviation of depression measurements used in the current study from other studies
Lucassen et al. (69) SPARX	Children and adolescents (age range: 12–19 years) 1. Transgender adolescents (N = 294; Age 12–15 = 131, Age 16–19 = 76) 2. Male adolescents (N = 4,135; Age 12–15 = 1,927, Age 16–19 = 977) 3. Female adolescents (N = 9,060; Age 12–15 = 3,595, Age 16–19 = 2,373)	- Patient health questionnaire –modified for adolescents	No follow-up	- Low completion rates (i.e., the completion of Module 4 in less than 10% of participants and the completion of Module 7 in less than 4% of participants - Significantly improved scores of patient health questionnaire modified for adolescents in male and female adolescents after the intervention but no change in scores in transgender adolescents	- The low completion rates - The restricted single sex/gender item in the used self-report (i.e., the limited effectiveness of the measurement for transgender adolescents)

IA, inattention; TOVA, test of variables of attention; BRIEF, Behavior Rating Inventory of Executive Function; CANTAB, Cambridge Neuropsychological Test Automated Battery; API, Attention Performance Index; ADHD-RS, ADHD rating scale; SSIS, social skills improvement system; IRS, impairment rating scale; CGI-I, Clinical Global Impressions-improvement; BASM, BCI ADHD severity Measure; CBCL, Child Behavior Checklist; PERMP, Permanent Product Measure of Performance; WJ-III, Woodcock-Johnson Third Edition; SDQ, Strengths and Difficulties Questionnaire; ERICA, Emotion-Regulation Index for Children and Adolescents; EATQ-R, Early Adolescent Temperament Questionnaire97Revised; FD-CMS, Functional and Dysfunctional Child Mood Scales; TS-VAS, Treatment Satisfaction Visual Analogue Scales; CASI, Child and Adolescent Scale of Irrationality; CATS-N/P, Children's Automatic Thoughts Scale-Negative/Positive; PAD, Profile of Affective Disorder; SCAS-C/P, Spence Children's Anxiety Scale - child & parent versions; ADIS-P, Anxiety Disorders Interview Schedule for DSM-IV, Parent version; PETS, Parent Expectancies for Therapy Scale; CSLK, Coping Strategies Checklist for Children; STAXI-CA, State Anger, Trait Anger, Anger Expression-Out, Anger Expression-In & Anger Control; CDRS-R, Children's depression rating scale-revised; OVK, Op Volle Kracht.