March 17, 2025
Background:
Noting that “the results of previous investigations into the therapeutic benefits of probiotics in the treatment of ADHD symptoms remain inconsistent,” a Taiwanese study team conducted a systematic search of the peer-reviewed medical literature to perform a meta-analysis.
The Study:
The team identified seven randomized controlled trials (RCTs) that met criteria for inclusion: focusing on children and adolescents under 18, with ADHD diagnoses, comparing probiotic interventions with placebo, and using standardized behavioral rating scales to assess ADHD symptoms.
Meta-analysis of these seven RCTs with a combined total of 342 participants found no significant improvement in ADHD symptoms. In fact, six of the seven RCTs clustered tightly around zero effect, while the seventh – a small sample (38) outlier – reported a very large effect size improvement.
Meta-analysis of the three RCTs with a combined 154 individuals that used probiotics with single strains of microorganisms showed absolutely no improvement in ADHD symptoms with no between-study variation (heterogeneity).
Meta-analysis of the four RCTs with a total of 188 participants that used multiple strains pointed to a medium – but statistically nonsignificant – effect size improvement, with high heterogeneity. Removing the previously mentioned outlier RCT collapsed the effect size to zero.
Two of the RCTs (with 72 total individuals), including the outlier, offered probiotics in conjunction with methylphenidate treatment. Meta-analysis of the other five RCTs with 270 persons that were structured around pure supplementation yielded absolutely no improvement in ADHD symptoms with no heterogeneity.
Meta-analyses of the four RCTs with a combined total of 238 participants that examined ADHD subtypes reported no effect on either inattention symptoms or hyperactivity/impulsivity symptoms.
Trivially, given the lack of efficacy, probiotic regimens were tolerated as well as placebo.
The Take-Away:
Ultimately, this meta-analysis found no evidence that probiotics improve ADHD symptoms in children and adolescents. Across seven randomized controlled trials, results consistently showed no significant benefit compared to a placebo. While probiotics were well-tolerated, they did not meaningfully impact inattention, hyperactivity, or impulsivity. These findings suggest that probiotics, whether single or multi-strain, are not an effective treatment for ADHD.
Shun-Chin Liang, Cheuk-Kwan Sun, Chih-Hua Chang, Yu-Shian Cheng, Ruu-Fen Tzang, Hsien-Jane Chiu, Ming Yu Wang, Ying-Chih Cheng, and Kuo-Chuan Hung, “Therapeutic efficacy of probiotics for symptoms of attention-deficit hyperactivity disorder in children and adolescents: meta-analysis,” BJPsych Open (2024) 10, e36, 1–8, https://doi.org/10.1192/bjo.2023.645.
Folic acid, also known as folate, is an essential vitamin(B-9). Inadequate dietary folate has been associated with abnormal fetal brain development. That suggests a deficiency could contribute to neurodevelopmental disorders, including ADHD.
If so, could folic acid supplementation for pregnant mothers help avoid ADHD in offspring?
A Chinese study team conducted a systematic search of the peer-reviewed medical journal literature looking for studies exploring neurodevelopmental effects associated with such supplementation.
It identified six studies that specifically looked for associations with offspring ADHD. A meta-analysis of these studies encompassing a total of 29,634 participants found a 14% (one in seven) reduction in the odds of ADHD in the offspring of mothers taking folate supplementation as opposed to children of mothers not doing so.
There was no sign of either publication bias or between-study heterogeneity.
The authors concluded, "Our meta-analysis indicated that appropriate maternal FA supplementation may have positive effects on offspring's neurodevelopmental outcomes, including improved intellectual development and reduced risk of autism traits, ADHD, behavioral, and language problems."
Given that folate is an essential vitamin in the first place, this suggests ensuring that pregnant women supplement their diet with folic acid. The authors further counseled, "However, further high-quality studies on this topic are needed to confirm the optimal dosage and the right time of FA supplementation and to investigate the underlying mechanisms."
Stimulant medications like methylphenidate and amphetamines are well-established treatments for reducing ADHD symptoms, making a notable difference in focus and behavior. Given that caffeine is also a stimulant, researchers have wondered whether it might offer similar benefits for managing ADHD symptoms. A recent meta-analysis conducted by a Brazilian research team sought to explore this question.
The researchers faced an immediate challenge: there is surprisingly little research directly investigating caffeine's effects on ADHD symptoms. After a thorough review of peer-reviewed literature, they identified only four randomized controlled trials (RCTs) suitable for their analysis, encompassing a combined total of just 152 participants.
The limited number of studies—and participants—meant that the meta-analysis was not as robust as the research team might have hoped. However, they proceeded to examine the available data to determine whether caffeine showed any measurable benefit over a placebo.
The results of the meta-analysis showed a slight decrease in ADHD symptoms among those who consumed caffeine compared to those given a placebo. However, this reduction was not statistically significant. The small sample size likely played a role in this outcome, making the study underpowered. Even if future studies with larger groups of participants were to show statistical significance, the observed effect size would likely remain too small to be clinically meaningful.
Interestingly, the four trials included in the meta-analysis showed very little variation in their findings. Each study slightly favored caffeine over placebo, but none came close to achieving statistical significance.
Ultimately, the researchers concluded that “overall, the totality of the evidence suggests no significant benefit of caffeine over placebo in the treatment of children with ADHD.” The findings indicate that while caffeine might produce a slight reduction in symptoms, it is not an effective alternative to established ADHD treatments like methylphenidate or amphetamines.
This study highlights the importance of relying on proven medications for ADHD management rather than seeking alternatives that lack substantial evidence. While caffeine might offer a slight stimulant effect, it falls short of delivering the therapeutic benefits needed for those with ADHD to manage their symptoms effectively. For clinicians, parents, and individuals with ADHD, these results underscore the value of evidence-based treatments in improving quality of life and daily functioning.
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.
Recent research suggests that inflammation may play a role in ADHD. Inflammation, marked by elevated proteins and cytokines, affects brain development and structure. Evidence suggests it plays a role in the development of ADHD, making the study of inflammatory markers crucial.
The platelet-to-lymphocyte ratio (PLR) is a cost-effective test for predicting outcomes of chronic inflammation and neuroimmune diseases. Studies show PLR may be an important inflammatory marker in the pathophysiology of ADHD in children.
The Study:
A Chinese study team used the National Health and Nutrition Examination Survey (NHANES) database maintained by the National Center for Health Statistics of the United States to investigate the association between PLR and ADHD in children aged 6–14.
The team identified ADHD through prescriptions of ADHD medications.
After exclusions for missing information, the study encompassed 1,455 children.
The authors adjusted for the following potential confounders: sex, age, race, poverty-to-income ratio, maternal age at childbirth, smoking during pregnancy, asthma, health insurance status, dietary inflammatory index, monocyte count, segmented neutrophil count, eosinophil count, and basophil count.
They also split the PLR results into quartiles, with the first quartile having the lowest readings.
Prescriptions of ADHD medications were twice as frequent among children in the second quartile as they were among children in the first quartile. They were four times as frequent among children in the third quartile than among children in the first quartile.
Conclusion:
The team concluded, “These findings further support the potential role of inflammation in the onset and development of ADHD, providing preliminary evidence for PLR as a potential biomarker for ADHD and suggesting its possible use in identifying high-risk populations. However, considering the limitations of this study, future research should be designed as larger-scale, prospective, multi-center randomized controlled trials to validate these findings and further explore the relationship between inflammatory mechanisms and ADHD.”
In other words, this study suggests that while high PLR values may serve as a potential biomarker for ADHD, particularly in specific high-risk groups, further research is needed to confirm these findings and fully understand the role of inflammation in ADHD development. Larger, more robust studies will be crucial to validating PLR as a reliable tool for identifying at-risk populations.
ADHD is the most prevalent neurodevelopmental disorder. Nearly 1% of pregnant women in the Nordic countries and more than 1% in the United States are prescribed ADHD medications, ranking these among the most commonly used medications during pregnancy. However, the safety of exposing a fetus to ADHD medications is still uncertain, prompting many expectant mothers to stop using them out of fear for their unborn child’s well-being.
The Study:
A European research team conducted a comprehensive nationwide study on the safety of ADHD medications during pregnancy using populations from Sweden and Denmark. The Swedish population was studied first, followed by inclusion of a separate study of the Danish population. Results were then combined through meta-analysis. Nordic countries, with their single-payer national health insurance systems and national population registers, facilitate the tracking of residents’ health from birth to death, thus providing robust data for such studies.
The team accounted for various potential confounders, including maternal age, year of delivery, whether the mother was a first-time parent, self-reported smoking during pregnancy, and any psychiatric history. They also considered psychiatric inpatient or outpatient treatment received within two years before pregnancy, as well as the dispensing of other psychotropic medications during pregnancy, including antidepressants, antipsychotics, antiseizure medications, and anti-anxiety medications. Additionally, they examined the highest level of maternal education and civil status at delivery (married or cohabiting compared to single, divorced, or widowed).
Out of 861,650 Swedish children, 2,257 were exposed to ADHD medications during pregnancy. Another 3,917 were born to mothers who discontinued ADHD medications before pregnancy.
Children exposed to ADHD medications had lower rates of ADHD, autism spectrum disorder, and overall neurodevelopmental disorders; however, none of these differences were significant.
Limiting the analysis to siblings to control for family environmental influences and genetics likewise found no significant differences.
A meta-analysis combining the Swedish results with a separately conducted nationwide population study in neighboring Denmark similarly found no significant differences between children exposed to ADHD medications during pregnancy and children born to mothers who discontinued ADHD medications before pregnancy.
Conclusion:
The team concluded, “Overall, our study provides reassuring evidence that continuing ADHD medication during pregnancy does not increase the risk of long-term NDDs [neurodevelopmental disorders] in offspring."
A new large-scale study has shed light on which treatments for attention-deficit/hyperactivity disorder (ADHD) in adults are most effective and best tolerated.
Researchers analyzed 113 randomized controlled trials involving nearly 15,000 adults diagnosed with ADHD. These studies included medications (like stimulants and atomoxetine), psychological therapies (such as cognitive behavioral therapy), and newer approaches like neurostimulation.
The Findings
Stimulant medications (lisdexamfetamine and methylphenidate) as well as selective norepinephrine reuptake inhibitors (SNRI) (atomoxetine) were the only treatments that consistently reduced core ADHD symptoms—both from the perspective of patients and clinicians. It may be worth noting that atomoxetine, while effective, was less well tolerated, with more people dropping out due to side effects.
Psychological therapies such as CBT, mindfulness, and psychoeducation showed some benefits, but mainly according to clinician ratings—not necessarily from the patients themselves. Neurostimulation techniques like transcranial direct current stimulation also showed some improvements, but only in limited contexts and with small sample sizes. Interestingly, none of the treatments—medication or otherwise—made a clear impact on long-term quality of life or emotional regulation.
Conclusion
So, what does this mean for people navigating ADHD in adulthood? Stimulant medications remain the most effective treatment for managing ADHD symptoms day-to-day but nonstimulant medication are not far behind, which is good given the problems we’ve had with stimulant shortages. This study also supports structured psychotherapy as a viable treatment option, especially when used in conjunction with medication.
The study emphasizes the importance of ongoing, long-term research and the need for treatment plans that are tailored to the individual ADHD patient– Managing adult ADHD effectively calls for flexible, patient-centered care.
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