March 4, 2021

Behavioral and Cognitive Impacts of Mindfulness-Based Interventions on Adults with ADHD

A Canadian team has published a systematic review examining the effectiveness of Mindfulness-Based Interventions (MBIs)for treating adults with ADHD. MBIs usually involves three forms of meditation –body scan, sitting meditation, and mindful yoga – that are intended to cultivate non-judgmental awareness of the present-moment experience. The team reviewed thirteen studies.

Three were single-group studies with no control group. One used dialectical behavior therapy (DBT). It reported mild to moderate improvements in ADHD symptoms, and substantial improvements in neurocognitive function (with standardized mean difference effect sizes from.99 to 2.22). A second enrolled both adults and adolescents in a mindful awareness program (MAP) which included a psychoeducational component. It found improvements in self-reported ADHD symptoms, with standardized mean difference(SMD) effect sizes running from .50 to.93. Following training, it also reported improvement in attentional conflict (.93) set-shifting (.43). The third study also used DBT, focused on acceptance, mindfulness, functional behavioral analysis, and psychoeducation. ADHD symptoms showed mild improvement (.22), and functional impairment was slightly reduced (.15) and remained stable at a 3-month follow-up.

The other ten studies used control groups. One used MAP and carefully stratified participants based on their ADHD medication status, then randomly assigned them to mindfulness treatment or waitlist. It reported large effect sizes in the improvement of self-reported and clinician ratings of ADHD symptoms (1.35 to 3.14), executive functioning (1.45 to 2.67), and self-reported emotion regulation (1.27 to 1.63). In another study, non randomly assigned adults to either mindfulness-based training (MBT) or skills training. Effect sizes were small to medium (.06 to .49), with 31% of MBT participants showing some improvement, versus only 11% of skills training participants.

Another study involved a controlled trial of college students with ADHD, randomized to receive either MBT or skills treatments. Treatment response rates were higher for MBT (59-65%, vs. 19-25%). At follow-up, the effect size for MBT on ADHD symptoms was large (.84), and similarly large on executive functioning (.81).

Another study tried a year’s worth of mindfulness training on poor responders to medication. Participants who received the treatment were compared to others who were waitlisted. The study reported a medium effect size (.63) in reducing the severity of ADHD.

Another looked at the impact of MAP on affective problems and impaired attention. It compared adults with ADHD and healthy controls who participated in MAP sessions with similar patients and controls who did not. The authors reported that MAP improved sustained attention and mood, with medium to large effect sizes (.50 to .80).

A recent study explored the impact of MAP on neurocognitive performance with a randomized controlled trial. Following an8-week mindfulness training, researchers “found a significant decrease in ADHD symptoms and significant improvement in task performance in both the MAP and the psychoeducation comparison group post - versus pre-intervention but did not find evidence for a significant main effect of treatment or a significant interaction effect on any ADHD symptoms (self-and observer-rated) nor on task performance (WM).”

Another study randomly assigned adults with ADHD either to a waitlist or to mindfulness-based cognitive therapy (MBCT). It found that MBCT led to a medium-to-large reduction in self-reported ADHD symptoms (.64) and a large reduction in investigator-reported symptoms (.78). It also found large (.93) improvements in executive functioning.

An 11th study looked at the effects of MBCT on neuropsychological correlates (event-related potentials(ERPs)) of performance monitoring in adults with ADHD. Half the patients were randomly assigned to MBCT, the other half to waitlist. MBCT produced reduced inattention, hyperactivity/impulsivity, and global ADHD index symptoms with medium to large effect sizes (.49 to .93).

A 12th study randomly assigned college students to MBCT or waitlist. At follow-up, participants who had received MBCT exhibited large (1.26) reductions in ADHD symptoms as well as greater treatment response rates (57%-71% vs. 23%-31%) versus waitlist. They also registered greater improvement on most neuropsychological performance and attentional scores.

Finally, another study compared the efficacy of MBCT plus treatment as usual (TAU) versus TAU only in reducing core symptoms in adults with ADHD. Participants were randomly assigned to an 8-weekly group therapy including meditation exercises, psycho education, and group discussions, or to TAU only, including pharmacotherapy and/or psycho education. At 6-month follow-up, MBCT+TAU patients reported large (SMD = .79) improvements in ADHD symptoms relative to TAU patients.

Overall, these are promising results for mindfulness-based interventions, and all the more so for those who do not respond well to drug therapy. Nevertheless, they must be seen as tentative. The sum total of participants over all thirten studies was just 753, or an average of only 58 per study. There was too much variation in the studies to perform a meta-analysis. Only one of the studies included a healthy (non-ADHD) control group. And only one study received a perfect sce by Cochrane Collaboration standards.  Most studies did not use a suitable control group, i.e., on in which there was an expectation of benefit from participating.  As the authors noted, “Attrition bias was found to have high or unclear risk in more than a half of the studies. The reason for dropout of participants was not always clearly specified in those studies, so it is difficult to decide if it might be related to adverse effects or to some discomfort with treatment or instead to some incidental reasons.”

Hélène Poissant, Adrianna Mendrek, Nadine Talbot, Bassam Khoury, and Jennifer Nolan, “Behavioral and Cognitive Impacts of Mindfulness-Based Interventions on Adults with Attention-Deficit Hyperactivity Disorder: A Systematic Review,” Behavioural Neurology, Vol. 2019, Article ID 5682050, 16 pages, https://doi.org/10.1155/2019/5682050.

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Meta-analysis finds little to no association between prenatal cannabis exposure and offspring ADHD

Meta-analysis Finds Little-to-No Association Between Prenatal Cannabis Exposure and Offspring ADHD

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:

  • It barely achieved statistical significance.
  • A few studies used more reliable clinical diagnoses, while most just used ADHD symptom rating scales.
  • It is virtually impossible to eliminate all confounding variables. Twin studies come closest to fully accounting for otherwise unmeasured environmental and genetic confounders, but no such studies were included.
  • The team made no effort to evaluate publication bias.  
  • Almost all the participants (497,821) were in a single study, and that study – which relied on clinical diagnoses – did not find a significant association.

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:

  • Two studies do not make for a robust meta-analysis, even more so with only 741 participants.
  • The result barely achieved statistical significance.
  • Publication bias was unaddressed.
  • Small effect sizes are questionable due to the virtual impossibility of eliminating all confounding variables, especially without twin studies.

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.

July 26, 2024

Meta-analysis Associates Dasotraline with Some Reduction in ADHD Symptoms

Meta-analysis Associates Dasotraline with Some Reduction in ADHD Symptoms

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.” 

July 25, 2024

Meta-Analysis: Young People with ADHD Experience Serious Social Cognition Impairments

Meta-analysis Concludes Children and Adolescents with ADHD Experience Serious Impairments in Social Cognition, Affecting Social Functioning

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: 

  • Theory of mind (ToM): Being able to attribute mental states to others, and thus explain and predict their behaviors. 
  • Empathy: Being able to feel an appropriate emotion in response to another person’s mental state, and thereby understand others’ feelings. 
  • Emotion recognition: Being able to identify emotions in facial expressions and other communication cues, such as voice and body position. 

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: 

  • Theory of mind (ToM): Meta-analysis of 49 studies with a total of 2,449 participants identified a large effect size impairment among children and adolescents with ADHD when compared with typically developing peers. Adjusting for covariates made no difference in the outcome. There was no sign of publication bias. 
  • Empathy: Meta-analysis of twelve studies combining 916 individuals yielded a medium effect size impairment among children and adolescents with ADHD. But there were strong signs of publication bias, and the outcome lost significance after adjusting for covariates (perhaps because it became under-powered with three studies pooling only 151 persons). 
  • Facial emotion recognition: Meta-analysis of 43 studies with a total of 3,369 participants reported a medium effect size impairment among children and adolescents with ADHD after adjusting for covariates. There was absolutely no indication of publication bias. 
  • Non-facial emotion recognition: Meta-analysis of eight studies encompassing 707 persons reported a small effect size impairment with signs of publication bias that became insignificant after adjusting for covariates. 

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.” 

July 22, 2024