research article

The Effects of Different Treatment Modes with Attention-Deficit/Hyperactivity Disorder: A MetaAnalysis of Randomized Controlled Trials

Xudong Yao#, Yang Yang#, Lan Zheng, Yalan Hu, Jianyan Peng, Fang Liu*

The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China, China

*Corresponding author: Fang Liu, The Clinical Hospital of Chengdu Brain Science Institute, University of Electronic Science and Technology of China, China

#The two authors contributed equally to this work.

Received Date: 21 November, 2022

Accepted Date: 02 December, 2022

Published Date: 06 December, 2022

Citation: Yao X, Yang Y, Zheng L, Hu Y, Peng J, et al. (2022) The Effects of Different Treatment Modes with Attention-Deficit/ Hyperactivity Disorder: a Meta-Analysis of Randomized Controlled Trials. Int J Nurs Health Care Res 5: 1369. DOI: https://doi.org/10.29011/26889501.101369

Abstract

Background: ADHD is associated with high rates of many adverse functional outcomes, including comorbid psychiatric disorders, academic impairments, accidents and injuries, driving accidents, and so on. It can be employed to alleviate symptoms and functions of ADHD with drug and non-drug treatment methods. Methods: A systematic review of studies published in PUBMED, EMBASE, Web of Science, and the Cochrane Library databases from Jan 01, 2010 until Jan 2021. Results: A total of 12 studies were included in the analysis of ADHD. The combined effect of drug treatment and placebo comparison was SMD= -6.84,95% CI(-10.48,- 3.21). According to subgroup analyses of methylphenidate and methylphenidate combined with other therapies in ADHD treatment, it is found that in hyperactivity/impulsivity subtype methylphenidate combined with other therapies in ADHD treatment is superior to drugs alone (SMD = -2.02, 95% CI, -3.61 to 0.43; I2 = 37%).It reveals no significant difference between drug therapy and physical therapy groups ((SMD =-7.41, 95% CI, -16.31 to 1.48; I2 = 95%). Discussion: Children with ADHD require a multi-mode treatment mode, simultaneously with drug treatment, mental health education should be provided, and other non-drug interventions should be combined according to specific functional and behavioral goals to facilitate the comprehensive recovery of children’s social function.

Keyword: ADHD; Pharmacotherapy; Non-pharmacotherapy

Introduction

ADHD is a common neurodevelopmental disorder characterized by symptoms of hyperactivity/impulsivity, inattention, or both [1], with prevalence rates of 3-5% in childhood [2,3]. As a result, adolescents and adults with underdeveloped attention, inhibitory control, and executive functions are at heightened risk for compromised driving safety. It is associated with high rates of many adverse functional outcomes, including comorbid psychiatric disorders, academic impairments, accidents and injuries, driving accidents, and so on [4]. In recent years, the deficiency of central neurotransmitter monoamines and related cytokines have been proved to be widely implicated in clinical treatment of ADHD patients, but obtaining satisfactory curative effect is difficult. In recent years, based on the characteristics of brain plasticity, scholars at home and abroad have paid increasing attention to drug combined executive function rehabilitation training for ADHD children to realize the targeted intervention of nerve defects. In terms of treatment, drug and non-drug treatment methods can be employed to alleviate symptoms and functions. Stimulants and non-doping drug treatments can quickly improve ADHD symptoms, but social function and academic level cannot be enhanced even for long-term use of drugs. Therefore, non-drug treatment for ADHD has garnered considerable attention, such as physical therapy, behavioral intervention, social skills training, and cognitive behavioral therapy [5,6]. At present, there is still controversy about ADHD treatment methods at home and abroad.

Methods

Literature Search

For nearly ten years, we searched PUBMED, EMBASE, Web of Science, and the Cochrane Library databases from Jan 01, 2010 until now. We also reviewed the reference lists of selected full-text articles. The search terms used were as follows: attention deficit disorders with hyperactivity, ADHD, atomoxetine hydrochloride, methylphenidate, non-drug treatment including group treatment, parental treatment, neurological treatment, placebo treatment, Randomized (and randomised) Controlled Trial (RCT), trial, child, and adolescent.

Study selection and inclusion criteria

The studies were included if they met the following criteria: (1) patients: participants met DSM-IV or DSM–5 ADHD criteria as determined by an interview with study staff or using a standardized, normed rating scale incorporating DSM criteria; (2) study type: RCT and double-blind trials with parallel group or placebo control group; (3) intervention type: study tested differences in MPA treatment, MPA in combination other medicines and nondrug therapies. Non-drug treatment methods include various treatments such as parent group treatment, psychotherapy, etc. (4) intervention duration: at least four weeks; (5) treatment goal was to reduce ADHD symptoms or related impairment; and (6) the main outcome index was the decrease in SNAP score, and the secondary index was symptom or syndrome score.

The exclusion criteria were as follows: case reports, conference abstracts, reviews, duplicates, and non-English studies. We included only randomized case-control studies published in peer-reviewed journals since the inception of databases. We limited our search to published studies to ensure a level of methodological adequacy and rigor among included studies and avoid inevitable problems with securing access to a full set of unpublished studies and bias that would introduce [7].

In the second step, all potentially eligible studies were reevaluated in full text. Data collection were extracted independently by two authors (F.L and Y.Y) using a predesigned extraction form that included the following data: title, year of publication, design of study (parallel vs. cross-over), blinding strategy, medication name, dropouts and adverse effects, the method used to evaluate results (questionnaires and scales to assess symptoms). In Jan 2021, we completed systematic searches of PubMed, EMBASE, Web of Science, and the Cochrane Library. We searched the full text of database entries using multiple combinations of search terms.

Literature quality evaluation

Jadad 3-item 5-point quality evaluation scale was used to evaluate randomization, double-blinding, withdrawal, or loss of follow-up. More than 3 points corresponded to high-quality literature, while 0 ~ 2 points corresponded to low-quality literature.

Statistical Methods

We used Comprehensive Meta-Analysis Version 3 to conduct all statistical analyses and generate data plots. For each study and measure listed previously, we calculated Hedges g and 95% Confidence Intervals (CIs) using means (Ms), SD, and sample sizes (N) in each group. For controlled studies, we calculated effects based on the difference between treatment and control groups at study outcome. For pre-to-post treatment change, we calculated Hedges g for pre-treatment versus post treatment scores using M, SD, and N at each time point for the treatment group. The studies were subjected to a heterogeneity test. When I2 < 50%, P > 0.1, homogeneity was good, and the fixed effect model was used to combine the effect quantity. On the contrary, the random effect model was used when the test results were heterogeneous and P < 0.01 was statistically significant.

Bias Assessment

Clinical trials suffered from significant publication bias, including detection and selection bias.

Results

Study Selection

Using electronic search engines and strategies, we identified 1497 articles. Of these, 1381 were excluded due to duplication and during the review of abstract and titles as they did not meet the inclusion criteria (Figure 1 for a flow chart of search). Following that, all titles fulfilling our inclusion criteria (116 studies) were reviewed in terms of abstract. When disagreements arose, reviewers consulted with each other until a consensus was reached. Ultimately, 46 full-text articles were retrieved for further screening, and 34 of these were excluded. Two independent reviewers collected and extracted data on ADHD status and diagnostic procedures, emotion regulation/dysregulation as defined above, gender composition (male, female), age, and comorbidity.

 

Figure 1: Flowchart for the selection of studies.

Participants

The meta-analysis included 1202 children and adolescents diagnosed with ADHD (males/females: 859/343). The subjects were diagnosed with ADHD by a psychiatrist or psychologist through clinical interview or using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) (American Psychiatric Association 2002). There were more boys than girls (71.46%).

Study Characteristics and Medications

This meta-analysis included 12 articles [8-19], including Pharmacotherapy of Methylphenidate (MPA), Atomoxetine (ATX), Guanfacine Extended-Release (Grx), Lisdexamfetamine Dimesylate (LDX), and tipepidine, as well as non-drug therapies such as psychotherapy, parent training, cognitive therapy, and placebo treatment.

Outcomes Measures

All studies analyzed absolute ADHD-RS-IV total symptom scores (Dupaul et al. 1998) and subtypes (inattention and hyperactivity/impulsivity). ADHD-RS-IV was selected for its internal consistency and concurrent validity with attention problems assessed using Achenbach scale.

Meta-Analysis Results

Meta-Analysis Results of Drug Treatment and Placebo Comparison

Revman 5.3 was used to test heterogeneity of included literatures, and the results revealed significant heterogeneity between studies(x2=31.38, P < 0.00001, I2 = 87%), necessitating the employment of a fixed-effect model. The results of forest plot indicated that rhombus was located on the left side of midline and did not intersect with the midline. The combined effect SMD = -6.84, 95% CI (-10.48, -3.21) indicates that clinical symptoms of ADHD drug treatment group were significantly alleviated compared with the placebo group, and the difference was statistically significant, as depicted in Figure 2.

 

Figure 2: Forest plot total score.

Subgroup analysis: according to ADHD-RS-IV scale score, there are hyperactivity/impulsivity and inattention subtypes, as illustrated in Figure 3. The results revealed statistically significant differences between the two subgroups (x2 = 30.57, P < 0.00001, I2 = 90%; X2 = 32.86, P < 0.00001, I2 = 91%), implying that the efficacy of drug therapy in children with ADHD is much better than that in placebo group.


Figure 3: Forest plot sub score.

According to subgroup analyses of methylphenidate and methylphenidate combined with other therapies in ADHD treatment (Figure 4), four studies found that the effect of drugs combined with other treatments was superior to that of drugs alone, but there was no significant difference in the ADHD total score (SMD = -2.95, 95% CI, -4.85 to -1.05; I2 = 0%). However, in hyperactivity/impulsivity subtype, methylphenidate combined with other therapies in ADHD treatment is superior to drugs alone (SMD = -2.02, 95% CI, -3.61 to 0.43; I2 = 37%) (Figure 5).

 

Figure 4: Forest plot total score.

 

Figure 5: Forest plot sub score.

Subgroup analyses were conducted to determine whether drug and physical therapies were different. Research revealed no significant difference between drug therapy and physical therapy groups ((SMD =-7.41, 95% CI, -16.31 to 1.48; I2 = 95%). Further analysis indicated that drug therapy had medium effect to physical therapy in inattention subtype (SMD =-0.78, 95% CI, -1.93 to 0.37; I2 = 89%), but no significant difference existed in hyperactivity/impulsivity subtype (SMD =-1.11, 95% CI, -2.21 to -0.01; I2 =93%) (Figure 6).

 

Figure 6: Forest plot total score.

 

Figure 7: Forest plot subscore.