Noting that “Oxidative stress disrupts the structure and function of neurons in the prefrontal lobe of the brain,” and “Structural and functional impairments in the prefrontal cortex have been shown to be highly correlated with behavioral and emotional problems of ADHD,” a Chinese team at Dalian University set out to systematically evaluate the safety and efficacy of antioxidant therapy in children and adolescents with ADHD.
The team’s systematic search of the peer-reviewed medical literature identified a total of 48 randomized controlled trials (RCTs) or prospective studies involving 12 antioxidant agents (resveratrol, pycnogenol, omega-3, omega-6, quercetin, phosphatidylserine, almond, vitamin D, zinc, folic acid, ginkgo biloba, Acetyl-L-carnitine) that met criteria for inclusion:
Treatment efficacy was measured through ADHD symptom scores using Conners’ parent rating scale (CPRS), Conners’ teacher rating scale (CTRS), ADHD rating scale-parent (ADHD RS-Parent), and ADHD rating scale-teacher (ADHD RS-Teacher), as well as secondary outcome indicators such as the Clinical Global Impressions scale (CGI) and Continuous Performance Test (CPT), relative to controls.
None of the antioxidant therapies were significantly better than placebo.
One limitation is that no effort was made to assess publication bias.
These results indicate that antioxidants should not be used for treating ADHD.
Antipsychotic medications are used to treat a variety of psychiatric disorders, including schizophrenia, bipolar disorder, sleeping problems, major depression, and severe anxiety.
Untreated maternal mental illness is associated with poor health outcomes for both mothers and their offspring. On the other hand, one must guard against any potential direct harms of medications on development – including neurological development – of the fetus.
Because prenatal use of antipsychotics is infrequent, previous observational studies have suffered from small sample sizes that have not enabled precise and reliable assessment of risk. The clinical decision about whether to continue antipsychotic treatment in patients who become pregnant has therefore remained inconclusive.
In search of more reliable guidance, an international study team conducted a systematic search of the peer-reviewed medical literature to perform the first meta-analysis on this topic.
They evaluated study quality and only included studies rated “good” or better.
Identification of ADHD was determined by clinical diagnosis.
Meta-analysis of four studies encompassing over eight million participants found a slight association. Children exposed to maternal antipsychotics during pregnancy were 11% more likely to be diagnosed with ADHD subsequently.
But even in observational studies with millions of participants, such associations – especially when slight to begin with – could be due to unmeasured confounders.
The team therefore compared children with gestational exposure to siblings from the same mother who were not exposed, to address shared genetic and social factors at the family level.
Meta-analysis of two population-based sibling-matched studies with a combined total of over 4.6 million participants in Denmark, Norway, Sweden, Finland, Iceland, and Hong Kong found no significant association between gestational exposure to antipsychotic medications and subsequent diagnosis of ADHD.
The team concluded, “Our systematic review and meta-analysis of observational studies indicates that the heightened risks of ADHD and ASD observed in children gestationally exposed to antipsychotics appear to be attributable to maternal characteristics, rather than having a causal relation to the antipsychotic itself.”
ADHD is associated with deficits in cognitive functions. These include such executive functions as reaction time, motor and interference inhibition, sustained attention, and working memory.
To what extent can ADHD medications compensate for such deficits? A recent meta-analysis by a European study team has explored this question. It suggests that while medication cannot completely reverse deficits in executive functions, it can lead to significant improvements.
Based on consistent evidence from many randomized double-blind controlled trials (RCTs) measuring behavioral improvements, first line treatment for ADHD is with stimulant medication while second-line treatment (for stimulant non-responders, or poor tolerability) is with non-stimulant medication (atomoxetine, viloxazine, guanfacine and clonidine).
This systematic literature search yielded eighteen RCTs, not all of which covered the same executive functions or medicines.
Meta-analyses yielded the following results:
Eleven RCTs, encompassing 925 participants, found a small-to-medium effect size improvement with methylphenidate. Variation (heterogeneity) among these studies was moderate, and there was no sign of publication bias.
Four RCTs with a total of 286 participants similarly reported a small-to-medium effect size improvement with atomoxetine. Again, heterogeneity was moderate, with no indication of publication bias.
Sixteen RCTs, with a combined 1,335 participants, found a medium effect size improvement with methylphenidate. Heterogeneity was moderate, and there was some indication of publication bias. No effort was made to correct for publication bias.
Three RCTs, encompassing 254 persons, found a medium effect size improvement with atomoxetine. Heterogeneity was moderate, with no evidence of publication bias.
Thirteen RCTs, with a total of 1,201 participants, found a small-to-medium effect size improvement with methylphenidate. Heterogeneity was moderate, with marginal indication of publication bias.
Six RCTs with a combined 753 individuals, reported a medium effect size improvement with atomoxetine. Heterogeneity was high, but there was no evidence of publication bias.
Nine RCTs, with a total of 1,025 participants, found a small-to-medium effect size improvement with methylphenidate. Heterogeneity was moderate, with no indication of publication bias.
Three RCTs with a combined 132 individuals, reported a statistically nonsignificant small-to-medium effect size improvement with atomoxetine. Heterogeneity was moderate, with no indication of publication bias. The nonsignificant outcome may have been due to the much smaller number of participants.
The team concluded, “these meta-analyses of chronic effects of stimulants and non-stimulants on executive functions in ADHD showed significant improvements with both methylphenidate and with atomoxetine in all cognitive domains tested with relatively similar effect sizes, and no statistical differences between them. The findings hence suggest comparable positive effects of both ADHD medication types on the most relevant executive functions in ADHD, suggesting for the first time that stimulant and non-stimulant ADHD medications, when taking [sic] longer-term, not only improve behavioural symptoms of ADHD, but also improve executive function performance, and to a similar degree.”
A placebo is a pill that does not contain any active medication. It is given to patients who form the control group in clinical trials. Comparing the effects of a treatment with placebo is essential because some patients will improve with the passage of time and some will get better due to the expectation of benefit they have from being enrolled in a clinical trial.
In studies of psychiatric conditions, patients in placebo groups typically show improvement. This can be induced by combinations of hope, suggestion, expectation, and consumption of what are presented as medications. It is reinforced by the context of receiving compassionate care from others, with supportive conversations.
A 2005 study found that placebo response is unequally distributed across psychiatric disorders, but did not address several disorders (including bipolar disorder) examined in the present meta-analysis conducted by a German research team.
Using only high-quality randomized clinical trials (RCTs) across major psychiatric diagnoses, the team quantified differences in the change of disorder symptoms within placebo groups.
They selected nine common and clinically significant psychiatric conditions: major depressive disorder (MDD), mania (bipolar disorder), schizophrenia, obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), generalized anxiety disorder (GAD), panic disorder, posttraumatic stress disorder (PTSD), and social phobia. For each of these, they selected the ten most recent high-quality RCTs of medicationsfor meta-analysis.
Of the ninety included RCTs, the team only looked at placebo groups. Because RCTs for the different diagnoses used differing established psychopathology rating scales, standardized pre-post effect sizes were used to compare outcomes across diagnoses.
Meta-analysis of the ten ADHD RCTs with a combined total of 1,189 participants reported large effect size improvements in symptoms, with no variation (heterogeneity) across RCTs and no sign of publication bias.
By contrast, the placebo effect size improvements in symptoms of major depressive disorder (10 RCTs, 1,598 participants) and generalized anxiety disorder (10 RCTs, 1,457 participants) were very large, well above those for ADHD, and with no overlap of 95% confidence intervals.
At the other end of the spectrum, the placebo effect size improvements in symptoms of schizophrenia (10 RCTs, 888 participants) were moderate, well below those for ADHD, and with no overlap of 95% confidence intervals.
There were absolutely no indications of publication bias.
The team noted, “In all diagnoses, there were improvements in symptom severity during placebo treatment (ie, the lower limit of the 95% CIs of the pooled pre-post placebo effect sizes were >0).” Although they stated, “The large and robust improvements observed in ADHD studies have not been reported to our knowledge.” they seemed to have missed this article by me and my colleagues: https://pubmed.ncbi.nlm.nih.gov/34232582/.
They also concluded, “Comparing the courses of different disorders under placebo indirectly may assist in understanding disease etiology, possibly providing insights into the proportionate influence of organic and psychogenic factors. Conditions with presumed substantial hereditary and biological components, such as schizophrenia, exhibited modest placebo responses in our analysis. Conversely, disorders with potentially less biological contribution, eg, depression and GAD, showed stronger responses. Our study may serve as an initial framework for incorporating the comprehensive insights derived from placebo groups of controlled trials into the etiopathogenetic exploration of mental illnesses.”
Quality of life (QoL) is defined as a person’s satisfaction with their life, measured across several dimensions including psychological, social, health, biological, and economic well-being. For adults, these are usually self-reported. QoL for children and adolescents is usually reported by parents.
Medications for ADHD include stimulants (methylphenidate and amphetamines) and non-stimulants (e.g., atomoxetine, clonidine, guanfacine, viloxazine). As QoL is related to ADHD symptoms’ severity, management of ADHD via medication could improve not only core symptoms but also QoL in people with ADHD.
Noting the absence of meta-analytic evidence on the effects of ADHD medications on QoL, an international research team conducted a systematic review and meta-analysis of parallel or cross-over randomized clinical trials (RCTs) to estimate the effects of ADHD medication on QoL. They also performed secondary analyses to see if these effects differed in children and adolescents versus adults, as well as by class of medications, and if they were moderated by length of treatment.
Meta-analyses of four RCTs with a combined total of 950 participants with ADHD (45% adults) found a medium effect size improvement among those receiving amphetamines by comparison with those receiving placebo. There was no sign of publication bias, but there was wide variation (heterogeneity) in effect size estimated among the studies.
Meta-analysis of four RCTs with a combined total of 1,094 participants with ADHD (57% adults) found a small-to-medium effect size improvement among those receiving methylphenidate by comparison with those receiving placebo. Again, there was no sign of publication bias, but wide variation in effect sizes among the studies.
Due to lack of sufficient data, the team could not explore whether length of treatment affected the results, or if there were differences between children/adolescents and adults.
Finally, a meta-analysis of eleven RCTs with a combined total of 3,344 participants with ADHD (63% adults) likewise found a small effect size improvement among those taking atomoxetine compared with those receiving placebo. Once again, there was no sign of publication bias, but wide variation in effect sizes among the studies.
The team was able to establish that for atomoxetine treatment, length of intervention – the studies ranged from 6 to 24 weeks – had no significant moderating effect. Similarly, they found no significant differences in effect on children and adolescents versus adults.
A single RCT evaluating modafinil treatment in adults found no improvements at any dose, whereas a single RCT testing non-stimulant guanfacine reported a medium effect size improvement in QoL. Modafinil is not FDA approved for ADHD but is sometimes used as a last resort if other treatments fail.
The team concluded that the FDA approved medications for ADHD were significantly more efficacious than placebo in improving QoL in people with ADHD. The improvements in Q0L were, however, smaller than what has been found for improvements is the symptoms of ADHD (inattention, hyperactivity, impulsivity). More work is needed to detect differences by age and length of treatment.
Lead’s neurotoxicity is well established, and organophosphate pesticides were deliberately developed first as nerve agents in warfare and then as insecticides.
Noting that “Epidemiologic research on chemical exposures associated with the development of ADHD is numerous; however, studies have employed various methods, and, in some cases, have resulted in seemingly conflicting results,” a U.S. study team has performed an updated meta-analysis applying “identical meta-analytic techniques to the literature on the associations between earlier chemical exposures and later ADHD.”
Lead
Meta-analysis of eleven studies reporting dichotomous outcomes with a combined 7,566 participants found children exposed to lead were almost twice as likely to subsequently be diagnosed with ADHD as their unexposed peers.
A second meta-analysis, of thirteen studies reporting continuous outcomes with a total of 1,775 participants, found a small effect size increase in ADHD diagnosis from exposure to lead.
Interestingly, meta-analysis of four studies with a combined 4,360 participants found no association between prenatal lead exposure and subsequent ADHD diagnosis.
On the other hand, meta-analysis of seven studies combining almost five thousand participants reported that cumulative lead exposure more than doubled the likelihood of subsequent ADHD.
In other words, it’s not so much prenatal exposure as exposure after birth that is associated with increased risk.
Organophosphates
Meta-analysis of four studies reporting continuous outcomes with a combined total of 692 persons likewise found a small effect size increase in ADHD diagnosis from exposure to organophosphates.
Mercury
Meta-analysis of six studies reporting continuous outcomes with a combined total of over 17 thousand participants found a tiny effect size increase in ADHD diagnosis from exposure to mercury.
On the other hand, meta-analysis of ten studies reporting dichotomous outcomes with a combined total of over 650,000 persons found no association whatsoever between mercury exposure and subsequent diagnosis of ADHD.
Other exposures
Meta-analysis of five studies involving more than 34,000 participants found no evidence of an association between exposure to anesthesia and ADHD.
Meta-analysis of three studies encompassing 1,739 individuals found no evidence of an association between exposure to cadmium and ADHD.
Meta-analysis of four studies combining more than 2,400 persons found no evidence of an association between exposure to hexachlorobenzene and ADHD.
A pair of meta-analyses, one of three studies reporting dichotomous outcomes including 2,050 participants, the other of nine studies reporting continuous outcomes involving almost three thousand participants, both found no evidence of an association between exposure to polychlorinated biphenyls (PCBs) and ADHD.
There was little variability (heterogeneity) among results reported by individual studies within these meta-analyses, but a serious limitation was the failure to check for publication bias.
The authors concluded, “given our findings related to exposure to mercury, organophosphates, and PCBs, further research may be helpful to better characterize these relationships. Many of our effect sizes were small, which is consistent with the literature indicating that many genetic and environmental factors contribute to ADHD. … Furthermore, our findings support existing regulations of certain chemicals,” and “may inform future regulatory decisions”
Quality of life (QoL) is defined as a person’s satisfaction with their life, measured across several dimensions including psychological, social, health, biological, and economic wellbeing. For adults, these are usually self-reported. In children and adolescents, they tend to be reported indirectly through parent- or caregiver questionnaires.
Medications for ADHD include stimulants (methylphenidate and amphetamines) and non-stimulants (e.g., atomoxetine, clonidine, guanfacine, viloxazine). As QoL is related to ADHD symptoms’ severity, management of ADHD via medication could improve not only core symptoms but also QoL in people with ADHD.
Noting the absence of meta-analytic evidence on the effects of ADHD medications on QoL, an international research team conducted a systematic review and meta-analysis of parallel or cross-over randomized clinical trials (RCTs) to estimate the effects of ADHD medication on QoL. They also performed secondary analyses to see if these effects differed in children and adolescents versus adults, as well as by class of medications, and if they were moderated by length of treatment.
Meta-analysis of four RCTs with a combined total of 950 participants with ADHD (45% adults) found a medium effect size improvement among those receiving amphetamines by comparison with those receiving placebo. There was no sign of publication bias, but there was wide variation (heterogeneity) in effect size estimated among the studies.
Meta-analysis of four RCTs with a combined total of 1,094 participants with ADHD (57% adults) found a small-to-medium effect size improvement among those receiving methylphenidate by comparison with those receiving placebo. Again, there was no sign of publication bias, but wide variation in effect sizes among the studies.
The team could not explore whether length of treatment with the stimulants methylphenidate or amphetamines affected the results, or a subgroup analysis to test any differences in effects on QoL between children/adolescents and adults, since less than ten studies were included in each of the meta-analyses.
Finally, meta-analysis of eleven RCTs with a combined total of 3,344 participants with ADHD (63% adults) likewise found a small effect size improvement among those taking atomoxetine compared with those receiving placebo. Once again, there was no sign of publication bias, but wide variation in effect sizes among the studies.
With more than ten studies, the team was able to establish that for atomoxetine treatment, length of intervention – the studies ranged from 6 to 24 weeks – had no significant moderating effect. Similarly, they found no significant differences in effect on children and adolescents versus adults.
A single RCT evaluating modafinil (a less addictive stimulant) treatment in adults found no improvements at any dose, whereas a single RCT testing non-stimulant guanfacine reported a medium effect size improvement in QoL.
The team concluded, “Overall, we found that methylphenidate, amphetamines, and atomoxetine were significantly more efficacious than placebo in improving QoL in people with ADHD. For atomoxetine, efficacy was significantly detected regardless of length of intervention or participant age ... our study demonstrated that, besides being efficacious in reducing ADHD symptomatology, stimulant and non-stimulant medications are effective in improving QoL in children, young people, and adults with ADHD, albeit with smaller effects compared those found for ADHD core symptoms severity. We found a medium effect for amphetamines and methylphenidate (both stimulant medications), and a small effect for atomoxetine (a non-stimulant).”
Prevalence of cannabis use among pregnant women is on the rise with the spread of legalization. The most frequently reported reasons for use are to relieve stress or anxiety, nausea or vomiting, pain, and for recreation.
Given that the primary psychoactive ingredient of cannabis, ∆9-tetrahydrocannabinol (THC) is a small fat-soluble molecule that can easily cross the placenta, an Israeli-U.S. research team conducted a systematic search of the peer-reviewed medical literature for studies exploring possible neuropsychiatric effects on offspring.
They included not only studies evaluating likelihood of ADHD, but also autism spectrum disorder, anxiety, depression, and psychotic symptoms. For each of these, adjustment was made for known confounding variables.
With that adjustment, meta-analysis of six studies with a total of over half a million (503,661) participants reported a 13% increase in the odds of ADHD in offspring of mothers using cannabis during pregnancy compared with offspring of mothers not using cannabis while pregnant.
That is generally considered a small effect size increase in risk. But there are multiple reasons to question even this minimal finding:
Meta-analysis of two studies with a total of 741 individuals reported a 20% increase in offspring use of cannabis among mothers who used cannabis during pregnancy, but once again this was subject to methodological shortcomings:
Some studies have suggested a link between cannabis and psychotic symptoms. But meta-analysis of four studies combining over nineteen thousand persons found no significant association between maternal cannabis use during pregnancy and offspring psychotic symptoms.
Many studies have pointed to commonalities in the etiology of ADHD and autism spectrum disorder (ASD). Yet meta-analysis of five studies encompassing over half a million participants found absolutely no association between maternal prenatal cannabis use and ASD.
The remaining meta-analyses also reported no association with depression or anxiety.
With the caution that absence of evidence is not the same as evidence of absence, it is by no means clear from what is presently known that prenatal cannabis exposure has any significant neuropsychiatric effects on offspring. And if further research finds any effects, they are likely to be minor.
Dasotraline is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) that had been under development by Sunovion for treating ADHD and binge eating disorder.
An Indian research team conducted a systematic search of the peer-reviewed medical literature to perform meta-analyses of the quantitative outcomes of clinical trials.
Meta-analysis of five double-blinded randomized clinical trials (RCTs) with a combined total of 1,498 participants reported a small-to-medium effect size reduction in ADHD symptoms in patients given dasotraline as opposed to those given placebo.
There were, however, strong indications of publication bias. Using the trim-and-fill procedure to correct for that bias yielded a small effect size reduction in ADHD symptoms in patients given dasotraline compared with those given placebo.
Insomnia were more than four times more frequent among patients given dasotraline than among those given placebo. There was no evidence of the frequency of insomnia being dose-dependent.
Similarly, patients given dasotraline were more than four times more likely to report decreased appetite than those receiving placebo. In this case, however, the effect was clearly dose-dependent, rising from 3x for 2mg to 4x for 4mg to 5x for 6mg and almost 8x for 8mg.
The authors concluded, “dasotraline can reduce the core symptoms of ADHD, that is, hyperactivity/impulsivity and inattentiveness, leading to an overall improvement of ADHD compared to placebo. Dasotraline can also improve clinician-determined patients’ global functioning compared to the placebo. The most common adverse drug reactions related to dasotraline were insomnia and decreased appetite. However, to fill the knowledge gap, multicentric randomized active-controlled clinical trials are warranted in this domain for a successful translation into clinical practice.”
Weighing these less than impressive initial results against the cost of further RCTs, Sunovion withdrew its application for approval by the Food and Drug Administration, stating, “while Sunovion considers dasotraline to be a promising, novel treatment for binge eating disorder and ADHD, we believe that further clinical studies would be needed to support a regulatory approval for dasotraline in these indications.”
Children and adolescents with ADHD are known to have difficulties in relating to family members, peers, and teachers. Over the long run this can contribute to anxiety or even delinquency.
Several cognitive functions that allow individuals to process social information and interact with others contribute to shaping everyday social interactions. These include:
A European research team performed a systematic search of the peer-reviewed medical literature to conduct meta-analyses of ToM, Empathy, Facial and Non-Facial Emotion Recognition in children and adolescents with ADHD when compared to typical development. As a comparison measure, they also included Everyday Social Skills (using self, parent, teacher, or clinician questionnaires/interviews of social skills) as an outcome.
The search yielded 142 case-control studies (including dissertations) with a total of 16,283 participants.
Meta-analysis of 82 studies with a combined total of 10,770 participants found a very large effect size impairment in everyday social skills among children and adolescents with ADHD when compared with typically developing peers. Adjusting for covariates only strengthened the finding. There was no sign of publication bias.
This was mirrored in three out of five measures of social cognition:
The team concluded, “Our findings show that children and adolescents with ADHD have deficits in ToM, Facial Emotion Recognition, and Everyday Social Skills, three domains that warrant clinical attention.”
There is increasing interest in digital interventions to treat ADHD symptoms and to overcome deficits in executive functioning that are associated with this disorder. Executive functions such as working memory and cognitive speed originate in the frontal lobes of the brain, and guide voluntary goal-directed behavior.
There is increasing interest in digital interventions to treat ADHD symptoms and to overcome deficits in executive functioning that are associated with this disorder. Executive functions such as working memory and cognitive speed originate in the frontal lobes of the brain, and guide voluntary goal-directed behavior. They affect reading speed and accuracy, reading comprehension, attention, and impulse control, among other behaviors important to the ability to function in social, educational, and professional environments.
A Swedish study team based at Umeå University recently conducted a systematic search of the medical literature to explore the efficacy of computerized cognitive training (CCT) to improve executive functioning in adults with ADHD.
They included published randomized controlled trials (RCTs) involving adults 18 to 65 years old with a primary diagnosis of ADHD. The controls were participants with either a passive (wait-list) or active (modified simple training) intervention.
Nine RCTs with a combined total of 285 participants met inclusion criteria. Lumping together all cognitive outcome types, meta-analysis reported a small effect size improvement that was just barely statistically significant (p = .048, with p < .05 as the boundary).
However, when separated out by individual outcome types – executive functioning, cognitive speed, general short-term memory, or ADHD symptom severity – the meta-analyses found no improvements that reached statistical significance.
Moreover, all RCTs except one were judged as high risk of bias.
While it is possible that additional studies enlarging the pool of participants could lead to statistical significance, all effect sizes were small to begin with, which is not encouraging.
The team concluded, “Considering the small positive effect in this meta-analysis for overall cognitive outcomes, together with the lack of evidence for far transfer, practitioners and individuals with ADHD should weigh the costs (resources and time) against the benefits of training.”
A South Korean study team recently concluded the first RCT-only meta-analysis of game-based digital therapeutics (DTx).
Combining 14 RCTs with a total of 1,183 participants, they found a small effect size improvement in parent-rated attention symptoms for game-based DTx interventions over controls. Nine RCTs combining 424 participants likewise found a small effect size improvement in teacher-rated attention symptoms. Between-study variation (heterogeneity) was negligible, and there was no indication of publication bias.
Combining five RCTs with a total of 256 participants, they reported small effect size improvements in both parent and teacher-rated hyperactivity/impulsivity symptoms. But they found no improvement in hyperactivity symptoms alone, whether evaluated by parents or teachers. Heterogeneity was in all instances negligible, with no sign of publication bias.
The team then compared game-based DTx interventions with pharmaceutical treatment.
ADHD medications outperformed game-based DTx interventions for improvement of attention symptoms in both parent (four RCTs with a total of 128 participants) and teacher (three RCTs with 92 participants) ratings, with small-to-medium effect sizes. Medications likewise prevailed in improving hyperactivity/impulsivity symptoms, whether rated by parents or teachers, with small-to-medium effect sizes.
The team concluded, “This study is the first direct and indirect meta-analysis to compare the efficacy of game-based DTx between control and medication according to the assessor in an RCT. In conclusion, game-based DTx had a more significant effect than the control. Additionally, between medication treatment versus DTx, medication was more effective.”
An international study team has just reported findings from a series of meta-analyses exploring associations between ADHD medications and headaches in children and adolescents.
An international study team has just reported findings from a series of meta-analyses exploring associations between ADHD medications and headaches in children and adolescents.
First, to compare headache occurrence in individuals with ADHD to those without ADHD, the team performed a very large meta-analysis of twelve studies with over 2.7 million children and adolescents. Those with ADHD had twice the rate of headaches.
There was no indication of publication bias, but there was considerable variation (heterogeneity) among studies, with crude odds ratios spanning from 0.9 to 3.37. Nevertheless, ten of the twelve studies pointed to higher odds among children and adolescents with ADHD. The four studies that controlled for age, sex, race, and other socioeconomic status variables reaffirmed the finding of a doubling of headache risk, this time with acceptable heterogeneity.
Three studies with a combined 7,755 participants found no difference in tension headaches, but five studies with over a quarter million persons found more than a doubling of the rate of migraine in children and adolescents with ADHD.
Next, the team performed meta-analyses of 58 randomized controlled trials (RCTs) of specific ADHD medications that met eligibility criteria for their systematic review. Because only a single eligible RCT apiece looked at bupropion and clonidine, these ADHD medications could not be included in the meta-analyses.
A meta-analysis of ten RCTs with a total of 2,672 participants found absolutely no association between use of amphetamines (including lisdexamphetamine) and headaches. Variation (heterogeneity) between studies was minimal, and there was no sign of publication bias.
A smaller meta-analysis of six RCTs with a combined 818 participants found a 24% increase in headaches among modafinil users, but it was not statistically significant, perhaps because of the much smaller combined sample size.
A meta-analysis of 17 RCTs with a total of 3,371 participants found a 33% increase in headache occurrence among methylphenidate users over placebo. Between-study variation (heterogeneity) was negligible, and there was absolutely no sign of publication bias.
Similarly, a meta-analysis of 22 RCTs with a combined 3,857 participants reported a 29% increase in headache occurrence among atomoxetine users over placebo. Again, heterogeneity between studies was negligible, with absolutely no indication of publication bias.
Finally, a meta-analysis of eight RCTs with 1,956 participants found a 43% increase in headache occurrence among guanfacine users over placebo. Once again, with negligible heterogeneity and no indication of publication bias.
ADHD is associated with impaired executive functioning. Executive functioning is a set of mental skills that include working memory, flexible thinking, and self-control. These are skills we use every day to learn, work, and manage daily life. Trouble with executive function can make it hard to focus, follow directions, and handle emotions.
ADHD is associated with impaired executive functioning. Executive functions are a set of mental skills that include working memory, flexible thinking, and self-control. These are skills we use every day to learn, work, and manage daily life. Trouble with executive function can make it hard to focus, follow directions, and handle emotions.
A Chinese study team searched for studies on non-pharmacological treatments of children and adolescents with ADHD aged 5 to 18 years intended to improve their executive functioning.
An initial methodological weakness was the decision to combine studies using formal ADHD diagnoses based on professional psychiatric manuals (DSM 3/4/5 and ICD 10/11) and studies relying on other methods such as parent reports.
This lack of rigor in identifying ADHD is surprising given that the team used studies that directly measured executive functioning through neurocognitive tasks, excluding those that relied on parent- or teacher-reported questionnaires.
67 studies involving 74 training interventions met the criteria. Meta-analysis of all these studies, encompassing a total of 3,101 participants, suggested medium-to-large effect size improvements in executive functioning. There was evidence of publication bias, but trim-and-fill adjustment increased the estimated effect size to large.
Nevertheless, there were further methodological shortcomings:
In this case, subgroup analysis mostly failed to explain the heterogeneity, with a single exception. Meta-analysis of the 16 studies with 744 participants that explored executive function-specific curriculum found small-to-medium effect size improvements, with no heterogeneity.
Unfortunately, the team did not perform a separate publication bias analysis on this subgroup, just as it failed to do so on any of the other subgroups.
By far the strongest evidence of benefit came from meta-analysis of the 17 studies with 558 participants evaluating physical exercise. Here the outcome pointed to very large effect size improvements in executive functioning. Yet once again, heterogeneity was extremely high. Breaking this down further between aerobic exercise and cognitively engaged physical exercise made no difference. Both types had the same very high effect size, with very wide heterogeneity. Again, there was no separate evaluation of publication bias on this group.
Meta-analyses of thirteen studies of neurofeedback combining 444 participants, and fifteen studies of cognitive training encompassing 727 participants, both pointed to just-short-of-large effect size improvements in executive function. Meta-analysis of twelve studies of game-based training with 598 participants indicated medium effect size gains. But again, in all three subgroups there was great variation between studies, and no analysis of publication bias.
While these meta-analyses are suggestive of efficacy, especially for physical exercise interventions, their methodological shortcomings mean we will have to await more rigorous meta-analyses to draw any more settled conclusions. Moreover, these meta-analyses did not evaluate the adequacy of the control groups used in the trials, which is a big shortcoming given prior work showing that the effect of non-pharmacologic treatments are very weak or non-existent when adequate controls are used.
Noting that the degree comorbidity (co-occurrence) of epilepsy and ADHD “has never been quantified based on a systematic review with meta-analysis,” a Chinese study team based at Wuhan university has just reported findings based on doing just that.
Noting that the degree of comorbidity (co-occurrence) between epilepsy and ADHD “has never been quantified based on a systematic review with meta-analysis,” a Chinese study team based at Wuhan university has just reported findings based on doing just that.
Their systematic search of the peer-reviewed medical literature yielded 17 studies examining the prevalence of epilepsy among persons with ADHD, and 49 studies measuring the prevalence of ADHD among persons with epilepsy.
According to the Apple dictionary app, epilepsy is “a neurological disorder marked by sudden recurrent episodes of sensory disturbance, loss of consciousness, or convulsions, associated with abnormal electrical activity in the brain.” Its lifetime prevalence in the general population is about 0.76%, or about one in every 130 persons.
Meta-analysis of 17 studies with a combined total of over 900,000 participants spread over twelve countries on five continents yielded an epilepsy prevalence estimate of 3.4% among individuals with ADHD, or well over four times the prevalence in the general population. There was no sign of publication bias, but variability (heterogeneity) among studies was extremely high.
The worldwide prevalence of ADHD in children, on the other hand, is about 7.2%, affecting roughly one in fourteen.
Meta-analysis of 49 studies with a combined total of 172,206 persons from 16 countries on five continents reported an ADHD prevalence of just over 22% among persons with epilepsy. However, heterogeneity among studies was extremely high, and there was very strong evidence of publication bias.
Using the trim-and-fill correction for publication bias yielded a reduced estimate of 16%, which is still over twice the prevalence in the general population.
Furthermore, the authors noted, “Given that the large sample studies in this study are basically population-based studies and the small sample studies are hospital-based studies, there is also the possibility of Berkson’s bias. Specifically, patients with comorbidities are more likely to need help or seek medical advice. This possibility would yield a higher comorbidity rate in hospital-based studies.”
And that is exactly what emerged from subgroup analysis. The prevalence of ADHD in epilepsy among the hospital-based studies was 27.1%, over twice the 13.2% prevalence reported from the 13 population-based studies. The largest population-based study, a U.S. study with over 114,000 participants, yielded a prevalence of only 3.5%.
The authors cautioned that the very high degree of heterogeneity between studies indicates “it is inappropriate to consider the summary effect as representative of the real effect.”
A key component of ADHD is inhibition dysfunction disorder. Inhibition function involves control of one’s attention, thought, emotions, and behavior. That enables individuals to overcome strong external temptations or internal tendencies, and become more focused.
ADHD often includes a problem called disinhibition. This means that the brain struggles to control attention, thoughts, emotions, and behavior, which can lead to negative outcomes. Normally, inhibition helps people stay focused and avoid distractions, but when it fails, it's called disinhibition.
Children with ADHD who have problems with inhibition may face issues like substance abuse, self-harm, and antisocial behavior. Improving their inhibition can help them better manage themselves, do well in school, and have better relationships.
A team of researchers from China and South Korea explored whether physical activity could improve inhibition in children with ADHD. They reviewed studies and excluded those without control groups, those with poor quality assessments, and those involving other interventions like cognitive training or supplements. Their final analysis included 11 studies with 713 participants.
Key Findings on Physical Activity
Conclusion
The research concluded that physical activity can significantly improve the inhibition in children with ADHD, especially with regular, moderate-to-vigorous, open-skilled exercise done at least twice a week for an hour or more. Future studies should continue to explore this with high-quality methods to confirm these findings.
Computerized cognitive training (CCT) uses computers to try to strengthen cognitive skills and processes, reduce ADHD symptoms, and improve executive functioning. Executive functions are cognitive processes and mental skills that help individuals plan, monitor, and successfully execute their goals.
Computerized cognitive training (CCT) uses computers to try to strengthen cognitive skills and processes, reduce ADHD symptoms, and improve executive functioning. Executive functions are cognitive processes and mental skills that help individuals plan, monitor, and successfully execute their goals.
CCT programs target one or more cognitive processes such as motor inhibition, interference inhibition, sustained attention, and working memory. They ramp up task difficulty as performance improves. The goal is to harness the brain’s inherent adaptability (neuroplasticity) to boost performance.
A European study team that previously probed the efficacy of CCT through meta-analysis had been unable to provide a robust estimate of effect size due to an insufficient number of high-quality trials with probably blinded outcomes. Noting that “there have been a considerable number of new RCTs [randomized controlled trials] published, many with larger samples, well-controlled designs and blinded outcomes,” the team performed an updated systematic review and meta-analysis.
They included RCTs with participants of any age who either had a clinical diagnosis of ADHD or were above cut-off on validated ADHD rating scales. RCTs had to have been peer-reviewed and published in an academic journal, and to have reported a validated outcome measure of ADHD symptoms, neuropsychological processes, and/or academic outcomes.
Fourteen RCTs with a combined total of 631 participants had probably blinded outcomes. Meta-analysis of these studies yielded no significant effect on either overall ADHD symptoms or hyperactivity/impulsivity symptoms. There was a marginally significant reduction in inattention symptoms, but the effect size was small. Between-study variation (heterogeneity) was negligible and there was no sign of publication bias.
Regarding academic outcomes, meta-analyses revealed no gain in arithmetic ability or reading fluency. There was a small but not statistically significant improvement in reading comprehension. Heterogeneity was minimal, with no indication of publication bias.
With two related exceptions, meta-analyses of RCTs measuring executive functions likewise reported no significant improvements in attention, interference inhibition (initial stage in controlling impulsive behavior), motor inhibition (follow-up stage in controlling impulsive behavior), non-verbal reasoning, processing speed, and set shifting (the ability to unconsciously shift attention between one task and another).
The exceptions were for working memory tasks. Meta-analysis of 15 RCTs with a combined 753 participants reported a highly significant small-to-medium effect size improvement in verbal working memory. A separate meta-analysis of nine RCTs with a total of 441 participants similarly reported a highly significant improvement in visuospatial working memory, this time with medium effect size.
The team concluded, “There was no empirical support for the use of CCT as a stand-alone intervention for ADHD symptoms based on the largest and most comprehensive meta-analysis of RCTs conducted to date. Small effects, of likely limited clinical importance, on inattention symptoms were found – but these were limited to the setting in which the intervention was delivered. Robust evidence of small- to-moderate improvements in visual-spatial and verbal STM/WM tasks did not transfer to other domains of executive functions or academic outcomes.”
Perfluoroalkylated substances (PFASs) – often described in the popular press as “forever chemicals” – are highly persistent pollutants.
Perfluoroalkylated substances (PFASs), commonly known as "forever chemicals" in the media, are pollutants that do not break down in the environment. Their chemical structure includes fluorine atoms bonded to carbon, which makes them effective at repelling water. This property has led to their use in water-repellent clothing, stain-resistant carpets and furniture, and nonstick cookware.
However, the same chemical structure that makes PFASs useful also makes them a concern for human and animal health, as there are no natural biological processes to remove them from the body. Once ingested, they accumulate and become more concentrated at each level of the food chain. PFASs can also cross the placental barrier, raising concerns about potential harm to developing embryos and fetuses.
A Chinese research team conducted a systematic review of the medical literature to examine if there is a link between maternal exposure to PFASs and an increased risk of ADHD in children. They analyzed data from several studies:
- A meta-analysis of five studies involving 2,513 mother-child pairs found no increase in ADHD risk from exposure to PFOA (perfluorooctanoate) or PFOS (perfluorooctane sulfonate). The consistency across these studies was high, with little variation and no evidence of publication bias.
- Another meta-analysis of three studies with 995 mother-child pairs also showed no increase in ADHD risk from exposure to PFNA (perfluorononanoate) or PFHxS (perfluorohexane sulfonate), with similarly negligible variation between studies and no publication bias.
- In an analysis comparing the highest and lowest quartiles of maternal exposure, a slight increase in ADHD risk was observed with PFOA exposure, while a slight decrease was noted with PFOS exposure. Both findings were marginally significant and may be due to the small sample sizes.
The researchers concluded that more studies are needed to confirm these findings due to the limited evidence available.
Guanfacine is a non-stimulant medication for ADHD. It is an Alpha-2 agonist that targets and excites receptors in the prefrontal cortex of the brain, the region that governs executive functions such as judgment, decision making, planning, and response suppression. These functions tend to be suboptimal in ADHD.
Guanfacine is a non-stimulant medication for ADHD. It is an Alpha-2 agonist that targets and excites receptors in the prefrontal cortex of the brain, the region that governs executive functions such as judgment, decision making, planning, and response suppression. These functions tend to be sub-optimal in ADHD.
Most treatment guidelines recommend stimulants as the preferred treatment for ADHD, because they respond faster, and studies show they have higher efficacy in reducing symptoms. But for individuals for whom treatment with stimulants is subpar, guidelines recommend non-stimulants as second-line treatment.
Previous meta-analyses have focused on efficacy among children and adolescents with ADHD. This meta-analysis, by a Chinese study team, expanded its reach to not only update the former, but also include studies of adults.
The team’s systematic search of the medical literature for double-blind randomized controlled trials (RCTs) identified eleven that could be combined for meta-analysis. With only a single study of efficacy for adults, however, no meta-analysis could be performed specific to persons 18 and older.
Meta-analysis of all eleven studies with a combined total of 2,623 participants found guanfacine to be roughly 75% more effective than placebo for reducing ADHD symptoms. Variation between studies (heterogeneity) was low. There was no sign of publication bias.
Breaking that down by length of time on guanfacine found no evidence of a dose-response effect, however. In fact, participants with less than ten weeks of treatment (seven RCTs, 1,771 participants) outperformed those with longer periods of treatment (four RCTs, 852 participants) with a narrow overlap in the 95% confidence limits.
The outcomes were also sensitive to the ADHD symptom scale used. Meta-analysis of RCTs using the Clinical Global Impression of Improvement treatment response score (four studies, 850 participants) reported no significant improvement, while RCTs relying on ADHD-Rating-Scale-IV (six studies, 1,128 participants) reported a significant improvement, but without providing a standardized effect size.
Finally, a meta-analysis of ten RCTs with a combined total of 2,273 persons found a 23% increase in treatment-emergent adverse events for guanfacine relative to placebo. The three most common such events in the guanfacine group were somnolence (38.6%), headache (20.5%), and fatigue (15.2%).
Noting “the incidence of parental obesity has been rising together with the prevalence of mental illness, suggesting a possible link between the two phenomena,” a Chinese study team performed a systematic search of the peer-reviewed literature on that topic.
Noting “the incidence of parental obesity has been rising together with the prevalence of mental illness, suggesting a possible link between the two phenomena,” a Chinese study team performed a systematic search of the peer-reviewed literature on that topic.
Further noting that previous meta-analyses have suggested a link between maternal obesity and increased risk of ADHD in offspring, they set out to also look at paternal obesity.
Only two studies, however, probed the relationship between paternal overweight and obesity and offspring ADHD, making that meta-analysis impractical. A meta-analysis of six studies with a combined total of over a hundred thousand participants found no significant association between overweight or obsess fathers and offspring mental disease of any kind (with all such disorders lumped together). There was no indication of publication bias and little variability (heterogeneity) between studies.
Ten studies with a combined total of over 800,000 participants, however, examined the relationship between overweight and obese mothers and offspring ADHD. Overweight mothers were twenty percent more likely to have offspring with ADHD. Obese mothers were more than fifty percent more likely to have offspring with ADHD. There was absolutely no sign of publication bias in either case. Inter-study heterogeneity was negligible for overweight, and moderate for obesity.
The team concluded, “We found that the most recent evidence indicates the detrimental connections between parental pre-pregnancy overweight/obesity and offspring mental health.” That is perhaps a bit overstated, as the only clear sign was with maternal overweight or obesity.
Neurofeedback, also known as EEG (electroencephalogram)biofeedback, is a treatment that seeks to alleviate symptoms of various neurological and mental health disorders, including ADHD. It does this through immediate feedback from a computer program that tracks a client's brainwave activity, then uses sound or visual signals to retrain these brain signals. This in principle enables patients to learn to regulate and improve their brain function and reduce symptoms.
An Iranian study team recently performed a systematic search of the peer-reviewed medical literature. It identified seventeen randomized-controlled trials (RCTs) of neurofeedback treatment for children and adolescents with ADHD that could be aggregated for meta-analysis.
A meta-analysis of twelve RCTs with a combined total of 740 youths looked at parent ratings of changes in hyperactivity/impulsivity symptoms, and separately of changes in inattention symptoms. In both instances, the net pooled effect centered on zero.
A meta-analysis of nine RCTs with a combined total of 787 youths examined teacher ratings. Once again, the pooled change hyperactivity/impulsivity symptoms centered on zero. For inattention symptoms, the teacher ratings centered on a tiny improvement, but it did not approach statistical significance. The 95% confidence interval stretched well into negative territory.
There was no sign of publication bias. Between-study heterogeneity, on the other hand, was high, with some small sample size RCTs pointing to reduced symptoms, and other small sample size RCTs pointing to increased symptoms. However, the RCTs with the larger sample sizes clustered close around zero effect size.
The authors concluded,"The results provide preliminary evidence that neurofeedback treatment is not an efficacious clinical method for ADHD."
Bipolar disorder is a severe mental illness that afflicts over one in fifty persons worldwide. About a quarter of those with bipolar disorder also has alcohol use disorder (AUD). This in turn complicates the treatment of their bipolar disorder. It exacerbates their symptoms, makes them more likely to be suicidal, and increases the risk of hospitalization.
More than one in five persons with bipolar disorder also have ADHD, which is likewise known to be correlated with AUD. To what extent does ADHD contribute to AUD in persons with comorbid bipolar disorder?
A European study team recently conducted a systematic search of the peer-reviewed medical literature to address that question. The team identified eleven studies with a combined total of 2,734 participants that could be aggregated to perform a meta-analysis.
They found that persons with comorbid ADHD and bipolar disorder were two and a half times more likely to be diagnosed with alcohol use disorder than persons with bipolar disorder but no ADHD.
Between-study heterogeneity was negligible, and there was no sign of publication bias.
The authors concluded, "At least a portion of the high rates of AUD in BD may, thereby, be related to comorbid ADHD. Longitudinal studies are needed to clarify the nature of this relationship."
Meta-analysis discovers clear link between mothers with PCOS and children with ADHD.
Polycystic ovary syndrome (PCOS) affects somewhere between 6 and 20% of women of reproductive age. Typical effects include:
· failure to ovulate;
· high levels of male hormones (androgens), which can lead to acne, seborrhea, hair loss on the scalp, increased body or facial hair, and infrequent or absent menstruation;
· metabolic disruption, including obesity and insulin resistance.
In pregnancy, PCOS is also known to increase the chances of birth complications.
Previous studies have suggested a link between maternal PCOS and ADHD.
A team of Arabian (Saudi and United Arab Emirates) researchers conducted a systematic review of the peer-reviewed medical literature and were able to identify four studies with a total of 1,354,182 participants that could be combined into a meta-analysis.
The meta-analysis found that children born to mothers with PCOS were 43% more likely to develop ADHD. The 95% confidence interval stretched from 35% to 51%, indicating a highly reliable finding.
Moreover, there was between-study variation: They all produced essentially identical results. There was also no sign of publication bias.
"However,"the authors noted, "the reported results do not necessarily provide definitive findings of a causal inference due to the randomized study design. All the included studies were observational in design." With this caution, they could only conclude that "the results of this meta-analysis showed that there might be a link between maternal PCOS and the risk of developing ASD and ADHD in the offspring."
Childhood antibiotic use is not found to be associated with development of ADHD
A Chinese research team recently conducted a systematic search of the peer-reviewed medical journal literature for studies exploring the association between childhood antibiotic exposure and subsequent diagnosis of ADHD in youths 18 years and younger.
A meta-analysis of six studies with a combined total of over 1.5 million participants found that children exposed to antibiotics were 18% more likely to later be diagnosed with ADHD.
There was absolutely no indication of publication bias. Between-study heterogeneity, on the other hand, was extremely high.
With such large cohorts, one can often tease out whether an association is causal, or due to genetic and familial confounding, by looking at matched close relatives.
Three of the studies, with a combined total of well over half a million participants, also compared matched siblings.
Significantly, the meta-analysis among matched siblings found no association whatsoever between childhood exposure to antibiotics and subsequent ADHD. Between-study heterogeneity was virtually nonexistent.
The team concluded, "Our meta-analysis indicated that early-life antibiotic exposure was associated with a subsequent increased risk of ASD or ADHD. However, such association was not found in the sibling-matched analysis, indicating that genetic and familial confounding factors may largely explain the observed association."
Based on current findings, repetitive transcranial magnetic stimulation cannot yet be officially recommended as an alternative neurotherapy for ADHD.
Noting that "despite a lack of solid evidence for their use, rTMS [repetitive transcranial magnetic stimulation]and tDCS [transcranial direct current stimulation] are already offered clinically and commercially in ADHD," and that a recent meta-analysis of ten tDCS studies found small but significant improvements in outcomes, but had several methodological shortcomings and did not include two studies reporting mostly null effects, a team of British neurologists performed a meta-analysis of all twelve sham-controlled, non-open-label, studies found in a comprehensive search of the peer-reviewed literature.
Ten of the twelve randomized-controlled trials used anodal stimulation of the dorsolateral prefrontal cortex, while the other two used anodal stimulation of the right inferior frontal cortex.
The trials explored several measures of cognition. The research team carried out a meta-analysis of all twelve trials, with a total of 232 participants, and found no significant improvement in attention scores from CDC, relative to sham stimulation. A second meta-analysis, of eleven trials with a total of 220 participants, assessed the efficacy of tDCS on improving inhibition scores, and again found no significant effect. A third meta-analysis, encompassing eight trials with a total of 124 participants, evaluated the efficacy of tDCS on improving processing speed scores, once again finding no significant effect.
The latter two meta-analyses approached the border of significance, prompting the authors to speculate that larger sample sizes could bring the results just over the threshold of significance. Even so, effect sizes would be small.
It is also possible that the trials focused on regions of the brain suboptimal for this objective, and thus the authors "cannot rule out the possibility that stimulation of other prefrontal regions (such as the right hemispheric inferior frontal cortex or dorsolateral prefrontal cortex or parietal regions), multiple session tDCS or tDCS in combination with cognitive training could improve clinically or cognitive functions in ADHD."
As to concerns about safety, on the other hand, "stimulation was well-tolerated overall."
The authors concluded that based on current evidence, tDCS of the dorsolateral prefrontal cortex cannot yet be recommended as an alternative Neurotherapy for ADHD.
According to Dexing Zhang et al., writing in the British Medical Bulletin, "Mindfulness is a moment-by-moment awareness of thoughts, feelings, bodily sensations, and surrounding environment. ... These practices can be formal (e.g. breathing, sitting, walking, body scan) or informal (e.g. mindfulness in everyday life).... Mindfulness is rooted in Buddhist traditions. However, it has become popular in recent years among various secular populations in healthcare, educational, and workplace settings: from pre-schoolchildren to older adults across the world." The two most widely adopted mindfulness-based interventions (MBIs) are mindfulness-based stress reduction and mindfulness-based cognitive therapy (Zhang, 2021).
An Italian research team recently conducted a comprehensive search of the peer-reviewed literature to identify studies exploring the efficacy of mindfulness-based treatments for ADHD. It found 31 studies that qualified for review, ten of which met the criteria for meta-analysis, with a total of 596 participants.
A meta-analysis of seven studies with a combined total of 489 participants found MBIs reduced ADHD symptoms with medium effect size and no sign of publication bias. When split into subgroups with and without active controls - in this case, psychoeducation and skills training groups -the outcomes diverged. In the three studies with non-active controls (187 participants), there was a large reduction in ADHD symptoms. In the four with active controls (302 participants), there was no significant difference.
A meta-analysis of ten studies with 596 participants found MBIs reduced inattention symptoms, with a medium-sized effect. Pooling the five studies without active controls (261 participants) produced a very large reduction in inattention symptoms. Once again, in the five studies with active controls (335 participants), there was no significant difference.
After adjusting for publication bias, a third meta-analysis of nine studies with 563 participants found no significant effect of MBIs hyperactivity symptoms. However, when limited to the five studies with-active controls (261 participants), it found a large reduction in hyperactivity symptoms.
After adjusting for publication bias, the fourth meta-analysis of four studies with a combined 243 participants found no significant improvement in executive function.
After adjusting for publication bias, a fifth meta-analysis combining six studies with 449 participants reported a moderate improvement in mindfulness skills. There was no significant improvement when looking only at the three studies with active controls (262 participants).
The team concluded that MBIs seemed to be effective in treating ADHD, but no more so than psychoeducation and skills training groups.
Yet they cautioned that the use of a waiting list for non-active controls muddies that conclusion: "It could be suggested that any intervention seems to have a significantly higher effect than WL [waiting list]in improving ADHD symptoms." This is a known hazard of using waiting lists as control groups (Cunningham, 2013).
Noting "the low general methodological quality," they stated, "From a clinical standpoint, according to the poor available evidence, we cannot conclude that MBIs are superior to other active [psychological] interventions in ameliorating all the considered outcomes, suggesting a role complementation and not as a replacement of the psychoeducation in the management of patients with ADHD, consistently with some guidelines' recommendations."
Meta-analysis show neurofeedback treatments resulted in no noticeable improvements in the working memory, response inhibition, or sustained attention of youth with ADHD.
Neurofeedback, also known as electroencephalogram (EEG) biofeedback, aims to help persons with ADHD train themselves to self-regulate patterns of brain activity associated with the disorder.
An example is theta-beta ratio frequency (TBR) training. Beta waves, with a frequency of 18 to 25 Hz, are associated with electrical activity when the brain is conscious or alert. Theta waves, with a frequency of 4 to 7 Hz, are associated with meditative, daydreaming, or drowsy states. In youths with ADHD, the theta to beta ratio tends to be elevated. TBR training seeks to reduce it.
Neurofeedback is often described as a promising emerging alternative or complement to pharmaceutical treatment. Previous meta-analyses have found neurofeedback can reduce symptoms of ADHD.
But what effect does it have on executive functions? A Thai research team based at Chiang Mai University conducted a comprehensive search of the peer-reviewed journal literature and identified ten studies with results suitable for meta-analysis.
A meta-analysis of all ten studies with a combined total, of 378 participants found no improvement whatsoever in response inhibition.
A second meta-analysis, of nine studies with a combined total of 349 participants, found no improvement in sustained attention.
Finally, a meta-analysis of three studies with a total of 121 participants likewise found no improvement in working memory.
In all three cases, there was no evidence of publication bias.
The authors concluded, "Results did not show the benefits of neurofeedback on executive functions assessed by neuropsychological tests."
With the growth of the Internet, we are flooded with information about attention deficit hyperactivity disorder from many sources, most of which aim to provide useful and compelling "facts" about the disorder. But, for the cautious reader, separating fact from opinion can be difficult when writers have not spelled out how they have come to decide that the information they present is factual.
My blog has several guidelines to reassure readers that the information they read about ADHD is up-to-date and dependable. They are as follows:
Nearly all the information presented is based on peer-reviewed publications in the scientific literature about ADHD. "Peer-reviewed" means that other scientists read the article and made suggestions for changes and approved that it was of sufficient quality for publication. I say "nearly all" because in some cases I've used books or other information published by colleagues who have a reputation for high-quality science.
When expressing certainty about putative facts, I am guided by the principles of evidence-based medicine, which recognizes that the degree to which we can be certain about the truth of scientific statements depends on several features of the scientific papers used to justify the statements, such as the number of studies available and the quality of the individual studies. For example, compare these two types of studies. One study gives drug X to 10 ADHD patients and reported that 7 improved. Another gave drug Y to 100 patients and a placebo to 100 other patients and used statistics to show that the rate of improvement was significantly greater in the drug-treated group. The second study is much better and much larger, so we should be more confident in its conclusions. The rules of evidence are fairly complex and can be viewed at the Oxford Center for Evidenced Based Medicine (OCEBM;http://www.cebm.net/).
The evidenced-based approach incorporates two types of information: a) the quality of the evidence and b) the magnitude of the treatment effect. The OCEBM levels of evidence quality are defined as follows (higher numbers are better:
Non-randomized, controlled studies. In these studies, the treatment group is compared to a group that receives a placebo treatment, which is a fake treatment not expected to work.
It is possible to have high-quality evidence proving that a treatment works but the treatment might not work very well. So it is important to consider the magnitude of the treatment effect, also called the "effect size" by statisticians. For ADHD, it is easiest to think about ranking treatments on a ten-point scale. The stimulant medications have a quality rating of 5 and also have the strongest magnitude of effect, about 9 or 10.Omega-3 fatty acid supplementation 'works' with a quality rating of 5, but the score for the magnitude of the effect is only 2, so it doesn't work very well. We have to take into account patient or parent preferences, comorbid conditions, prior response to treatment, and other issues when choosing a treatment for a specific patient, but we can only use an evidence-based approach when deciding which treatments are well-supported as helpful for a disorder.
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