The study protocol (registered on the ClinicalTrials website: NCT04355065) is published elsewhere [46], but it is basically a prospective, unicentric, randomized, non-equality trial in 105 patients with ADHD. All participants were clinically stable before baseline. Subjects were randomized into 3 groups: TC group (electronic cognitive training with TC), TSTM group (cognitive training using TSTM), and CG (patients were called by phone every week, but they received no cognitive intervention). The allocation ratio was equal in all 3 groups (n=35 per branch).

The study was approved by the Ethics Committee of the Puerta de Hierro University Hospital in Majadahonda on December 2, 2019 (PI 187/19).

The clinical trial included children, adolescents, and young adults between the ages of 12 and 22 years (mean age 14.38, SD 2.26 years). The minimum participation age was 12 because virtual reality is discouraged for children younger than 12 years. The maximum age was 22 because brain maturation continues until that age, approximately [47,48]. Furthermore, adolescent patients admitted in Child and Adolescent Psychiatry units are progressively referred to be followed up in Adult Psychiatry services, which means that patients up to the age of 20 (and occasionally 22) years are already followed up in Child and Adolescent Psychiatry units [46]. Inclusion criteria were as follows: adolescents or young adults between the ages of 12 and 22 years with a diagnosis of ADHD and clinically stable on any medication related to ADHD, meaning that participants had a consistent drug prescription and were not allowed to change it during their participation; however, during the trial, 5 participants changed their medication, another 5 participants increased their medication dosages, another 5 participants decreased their medication dosages, and medication was removed for another participant. Exclusion criteria were the following: comorbidities with autism or intellectual disability, epilepsy, or another severe clinical condition; plans to begin another clinical treatment or moving out during the following 3 months; and risk of suicide [46]. A total of 105 patients (35 per group) were recruited for the clinical trial, of which 47 (45.2%) had an inattentive ADHD subtype and 57 (54.8%) had a mixed ADHD subtype.

The participants were recruited between December 18, 2019, and November 16, 2020. The last evaluation was performed on February 6, 2021.

To warrant clinical trial randomization, AR generated a sequence of random numbers through Epidat 4.2 software (Dirección Xeral de Saúde Pública, Xunta de Galicia). The 105 patients were randomly assigned to the 3 groups by HBF following the randomized sequence. Each randomization number was introduced inside a closed, opaque envelope. When a patient came to the hospital to participate in the trial, the inclusion and exclusion criteria were applied to them (one participant was excluded then); the patients and their parents received and signed informed consents, and after the first assessment (D0), each participant received and opened the envelope corresponding to their inclusion number, and the group assigned to that number.

A total of 105 patients agreed to participate in the trial and signed a reported consent form. Ultimately, 1 patient was excluded for having a previously unreported history of epilepsy. The other 104 patients were randomized to one of 3 groups: TSTM (n=35), TC (n=34), and CG (n=35). Figure 1 shows a flow diagram describing in detail the number of participants in each trial stage.

In the PP population at D90, participants were male in 71.9% (64/89) of the cases (TSTM group: 27/31, 87.1%; TC group: 19/24, 79.2%; and CG: 18/34, 53.1%). The mean ages for the groups were 14.7 (SD 2.4) for TSTM, 13.8 (SD 1.9) for TC, and 14.8 (SD 2.4) for CG. Table 1 and Table 2 show all the sociodemographic and baseline variables.

The BRIEF-2 questionnaire shows that the TSTM group performed better than the TC and CG groups in “working memory,” “planification and organization,” and “cognitive regulation" scales, the groups being approximately equal in the rest of the BRIEF-2 scales (Tables S1 and S2 in Multimedia Appendix 1 present descriptive baseline characteristics).

For both primary and secondary outcomes, we calculated individual pre-post differences and used these differences as the dependent variables in our tests.

The goal of this study was ultimately to compare the changes between D0 and D90 in every group as well as the differences among groups. The main measurement for testing the differences were the BRIEF-2 scores, according to the indications already presented elsewhere [46]. The groups were compared through Kruskal-Wallis tests.

ATI showed improvements for the TC group compared to the CG group in “emotional control” and “emotional regulation” (P<.10) scores. PP also showed a significant difference in “emotional control” between the TC and CG groups (P<.10). None of the rest of the comparisons reached a statistical significance. All tests and significance levels are shown in Tables 3 and Table 4.

Analyses for secondary outcomes were performed in the PP population. Table 5 shows all the tests and significance levels for the secondary outcomes. Table 5 highlights those variables that reached significance in Kruskal-Wallis tests and the pairwise comparisons between the three trial groups.

According to the protocol study of our add-on clinical trial [46], scores on ADHD-5, CPRS, SNAP-IV, ATENTO, BarOn EQ-i:YV, and CPT-3 tests are considered secondary end point analyses. The groups were compared by means of Kruskal-Wallis tests and, subsequently, Mann-Whitney tests. Neither SNAP-IV nor CPRS-HI scores showed significant differences between CG and any of the other groups. ATENTO (parents’ reports) showed no significant differences between the CG and the other groups.

ATENTO (self-report) scores showed a significant difference between the TSTM and CG groups in “school context” (P<.10). Additionally, the TC group showed a statistically significant difference with the CG in “time orientation” measures. None of the other comparisons reached statistical significance.

BarOn EQ-i:YV scores showed statistically significant differences between the TSTM and CG groups in “positive impression” on the interpersonal scales (P<.10). None of the remaining comparisons reached statistical significance.

CPT-3 scores showed differential improvements in “block change” and “inter stimulus change” in the TSTM group compared with the control group and differences in improvements in “block change” between the TC and control groups (P<.10). None of the other comparisons reached statistical significance.

This prospective, unicentric, randomized study in clinically drug-stable children with ADHD did not confirm our hypothesis that using an augmentation strategy (either TSTM or TC) may improve executive functions as measured by the BRIEF-2 total scores. An exception was the improvement in emotional control and regulation as measured by the BRIEF-2 in the TC group. Furthermore, significant pre-post symptom reductions were found for several scales measuring secondary end points, and they differ depending on the type of intervention (as explained in the following sections).

We found no improvements in executive functioning after using TSTM. This finding is consistent with literature using other serious video games such as ACTIVATE [60] or Plan-It Commander [61]. However, this last video game demonstrated improvements in working memory and planification skills, which have not been observed in our study. In addition, a recent review found that some video games may be beneficial for executive function training in patients with ADHD [62].

However, we found that the TSTM group showed better posttreatment scores in core ADHD symptoms, in particular inattentive symptoms, compared to the CG, mainly in self-reported tests. Moreover, parents reported improvements in social and school skills, consistent with results coming from studies using other serious video games like Plan-It Commander [61] and ThinkRx [63].

But the most relevant finding is that the TSTM group, compared to the CG, showed some improvement in some emotional domains. Both self-reports and parent reports provided better scores on scales related to emotional intelligence, emotional regulation, and performance in school context compared to the CG, which is in keeping with some other literature [64-67]. Better than a purely cognitive tool, the TSTM video game may serve as a way to train and improve self-regulation and social skills through facing challenging problems and competitions with a social component.

As was the case with TSTM, we did not find any improvement in the TC group when compared with the CG, with the remarkable exception of emotional control and regulation. This negative finding is in contradiction with several studies reporting improvements in executive functioning using a therapy based on board games (eg, chess and Go) [31]. Demily et al [68] reported that patients with schizophrenia who played chess for just 10 sessions improved executive functioning (z=–3.41). Finally, a recent systematic review and meta-analysis suggested that some of these board games may improve self-efficacy, attitudes, social functioning, and executive functions [69]. Our negative findings might be explained either by differences in the studied populations (the studies were devoted to patients with diagnoses apart from ADHD) or that TC was implemented electronically.

However, core ADHD symptoms benefited from TC. In particular, inattentive symptoms improved most in the TC group when compared with the CG. This result is consistent with that obtained in a pilot study using chess in children with ADHD [28]. Furthermore, as was the case with TSTM, the greatest improvements obtained by TC training were in the emotional and interpersonal spheres. Significantly better improvements were shown in emotional intelligence, emotional regulation and control, as well as interpersonal scales, as measured by the BRIEF-2 and BarOn EQ-i:YV scores. Our findings are in keeping with previous studies reporting that chess training has shown good results in emotional intelligence development [30,70].

The main strength of this study is the use of 2 gaming strategies for treating ADHD, following an add-on strategy with clinically stable patients; one of them was disruptive—the use of a serious video game (TSTM)—and the other (TC) was more traditional, thus allowing for testing the effectiveness of each tool in executive functions and ADHD core symptoms. In contrast, the main limitation was the irruption of the COVID-19 pandemic, which impacted the clinical trial, as some patients randomized to the TSTM group had more difficulty completing the cognitive training sessions. Another limitation was the use of just one TSTM session per week in the TSTM group, which may have limited the effectiveness of this cognitive training. Accordingly, we plan to include a 2-3 session-per-week strategy in the next clinical trial using TSTM, scheduled to begin in April 2023. Furthermore, the evaluation was not blind and was based on clinical judgment and either self-report or parental reports. However, previous work states that teachers, rather than parents, tend to be the most reliable external observers of ADHD symptoms in children [71]. Furthermore, we used the CPT-3 to have an objective measure of our results. Another limitation was the difference between the ATI and the PP populations. Samples sizes for the groups were not very different, but a potential survival bias may have conditioned our results. It is possible that adherence to treatment was conditioned by the differential attractiveness of the video game and TC, that is, children who like video games or chess were more likely to complete the trial, and that could bias the results for the PP population. Indeed, in the PP analyses, fewer patients finished the TC intervention in the TC group. It is possible that only those patients with ADHD who were motivated or who liked chess finished the treatment, thus biasing our results in the TC arm. Another difference is the alternate location of the TSTM treatment, administered in our hospital, compared to the TC treatment, self-administered at the patients’ homes. Moreover, a possible limitation is the use of drug-stable samples; perhaps the effects of playing serious video games or TC may be more prominent in patients without a stable pharmacological treatment. Furthermore, to have clinical samples as representative and general as possible, we recruited participants in a wide age range, but our samples were not large enough to allow for analyses across developmental stages; future research should study in depth the differential effects across ages. Finally, the lack of a long-term follow-up approach kept us from studying the maintenance of any beneficial effect over time.

Neither TSTM nor TC produced a significant improvement in the executive functioning of patients with ADHD who were clinically stable on ADHD drugs. However, both TSTM and TC produced a significant improvement in some ADHD symptoms, particularly in emotional regulation areas. Further studies are warranted to extend these preliminary but motivating findings.