July 16, 2021

What do we know about the relationship between omega-3 PUFAs and ADHD?

There has been much interest in omega-3 Polyunsaturated fatty acids (PUFAs) as treatments for ADHD. Humans are unable to synthesize the omega-3 PUFA alpha-linolenic acid (ALA)and the omega-6 PUFA linoleic acid (LA), and must therefore obtain these through food, which is why they are known as essential fatty acids.  Because cells in the brain need omega-3 PUFAs, they have been studied as a treatment for ADHD by many researchers.  Several meta-analyses are available.

A 2014 meta-analysis by Elizabeth Haw key and Joel Niggcombined nine studies involving 586 participants. It found mean blood levels of omega-3 PUFAs in persons with ADHD to be lower than in controls. The standardized mean difference (SMD) effect size was medium (SMD = .42, 95% CI = .26-.59), with less than a one in one thousand probability of such a result being obtained by chance alone. Adjusting for publication bias reduced the effect size slightly to .36 with a 95% CI of .21-.51, in the small-to-medium range. The authors then examined whether omega-3 supplementation could help alleviate ADHD symptoms. Combining 16 studies with 1,408 participants, they found improvements, but this time with a small effect size (SMD = .26, 95% CI =.15-.37), again with less than a one in a thousand probability of such a result being observed by chance. Adjusting for publication bias reduced the effect size to .16 with a 95% CI of .03-.28.  For comparison, the SMD for stimulants is about 0.9.

Another meta-analysis conducted in the same year by BasantPuri and Julian Martins combined 18 PUFA supplementation studies involving1,640 participants. They also found a small effect size for reduced ADHD symptoms (SMD = .19, 95% CI = .09-.30, p<.001). Adjusting for publication bias further reduced the effect size to a paltry and statistically insignificant level (SMD = .12, 95% CI = -.01-.25). It should be noted that while16 of the studies involved omega-3 supplementation, two involved only omega-6supplementation. Yet the results for the latter did not differ noticeably from the former. When the authors limited the analysis to the 11 studies specifically including both the omega-6GLAand the omega-3 EPA, the effect size for reducing inattention symptoms was a bit higher(SMD = .31, 95% CI = .16-.46, p<.0001). But the results were not significantly different from those for the studies without the GLA+ALA combination (.012; 95% CI: .161-.137; p=.875). Publication bias was not addressed, and the hunt for a highly specific subset with positive results may have produced a false-positive finding.  The authors conceded, "Weaknesses of this study include the following: although the pooled effect was statistically significant, only two studies showed a significant effect by themselves; the funnel plot showed evidence of publication bias; there was evidence of reporting bias; few studies were formally registered; study methodological quality was variable, and the placebo used across studies varied."

A 2016 meta-analysis by Laura Lachance et al. tried looking for differences in the ratio of omega-6 to omega-3 PUFAs, and more specifically, AA to EPA, in the blood of persons with ADHD versus normally developing persons. Pooling five studies with485 participants, it found the omega-6 to omega-3 ratio to be significantly higher in persons with ADHD, and pooling three studies with 279 participants, it likewise found the AA to EPA ratio significantly higher.

A 2017 meta-analysis by Jane Pei-Chen Chang et al. Reexamined comparative levels of omega-3 PUFAs in ADHD patients versus normally developing controls. Combining six studies with 396 participants, ADHD patients had lower levels in blood and mouth tissue, with a medium effect size (SMD =.38) that was not statistically significant (p=.14).  Omega-6 levels were indistinguishable (SMD =.03) in the two groups. AA (SMD = .18, p=.33) and EPA (SMD = .25, p=.17) levels were slightly lower, but once again statistically not significant. DHA levels were lower as well, this time with a medium effect size (SMD = .56), but at the outer margin of significance (p=.05). Only by dropping one study were the authors able to claim significance for EPA, AA, and omega-3 differences.

Chang et al. also performed a meta-analysis of supplementation studies. Combining seven studies with 534 participants, they found a small to medium reduction in ADHD symptoms with omega-3 supplementation(SMD = .38, 95% CI = .2-.56, p<.0001). Corrections for publication bias were not reported. The authors also reported large reductions in both omission errors (SMD = 1.09, 95% CI = .43-.1.75, p<.001) and commission errors (SMD =2.14, 95% CI = 1.24-3.03, p<.00001) on a neuropsychological test of attention. But the former involved only 3 studies with 214 participants, and the latter only two studies with 85 participants.

Also in 2017, Pelsser et al. published a systematic review that identified only two meta-analyses of double-blind, placebo-controlled trials of PUFA supplementation. One of those, a 2012meta-analysis by Gillies et al., found no statistically significant declines in either parent-rated ADHD symptoms (five trials, 413 participants, SMD = -.17,95% CI = -.38-.03) or teacher-rated ADHD symptoms (four trials, 324participants, SMD = .05, 95% CI = -.18-.27). The other, a 2013 meta-analysis by Sonuga-Barke et al., found only a slight and barely statistically significant reduction in symptoms (11 trials, 827 participants, SMD = .16, 95% CI =.01-.31). Pelsser et al. concluded, "Considering the small average ESs [effect sizes] PUFA supplementation is unlikely to provide a tangible contribution to ADHD treatment."

Putting all of this together, there are indications that individuals with ADHD may have lower levels of omega-3 PUFAs, and that omega-3 supplementation may slightly reduce symptoms of ADHD, but the evidence remains inconclusive, with at best small effect sizes. It is possible, but not yet demonstrated, that omega-3 PUFAs might produce good outcomes in a small subset of patients.

Jane Pei-Chen Chang, Kuan-Pin Su, Valeria Mondelli, and carmine M Pariante, "Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder: a Systematic Review and Meta-Analysis of Clinical Trials and Biological Studies," Neuropsychopharmacology (2017),43(3): 534-545.
Donna Gillies, John KH Sinn, Sagar S Lad, Matthew J Leach, MelissaJ Ross, "Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents," Cochrane Database of Systematic Reviews (2012), DOI:10.1002/14651858.CD007986.pub2.
Elizabeth Hawkey and Joel T. Negg, "Omega-3 fatty acid and ADHD: Blood level analysis and meta-analytic extension of supplementation trials," Clinical Psychology Review(2014), 34(6), 496-505.
Laura LaChance, Kwame McKenzie, Valerie H. Taylor, and Simone N. Vigod, "Omega-6 to Omega-3 Fatty Acid Ratio in Patients with ADHD: AMeta-Analysis," Journal of the Canadian Academy of Child and AdolescentPsychiatry (2016), 25(2), 87-96.
Lidy M. Pelsser, Klaas Frankena, Jan Toorman, Rob Rodrigues Pereira, "Diet and ADHD, Reviewing the Evidence: A Systematic Review of meta-Analyses of Double-Blind Placebo-Controlled Trials Evaluating the Efficacy of Diet Interventions on the Behavior of Children with ADHD," PLOS ONE (January 25, 2017), 1-25.
Basant K. Puri and Julian G. Martins, "Which polyunsaturated fatty acids are active in children with attention-deficit hyperactivity disorder receiving PUFA supplementation? A fatty acid validated meta-regression analysis of randomized controlled trials," Prostaglandins, Leukotrienes and Essential Fatty Acids (2014), 90, 179-189.
Edmund J.S. Sonuga-Barke et al., "NonpharmacologicalInterventions for ADHD: Systematic Review and Meta-Analyses of RandomizedControlled Trials of Dietary and Psychological Treatments," American Journal of Psychiatry (2013),170:275-289.

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Updated Analysis of ADHD Prevalence in the United States: 2018-2021

Attention-Deficit/Hyperactivity Disorder (ADHD) remains a prevalent condition among children and adolescents in the United States. A recent analysis based on the National Health Interview Survey (NHIS), conducted by the National Center for Health Statistics at the CDC, provides an updated look at ADHD prevalence from 2018 to 2021. Here’s a closer look at what the data reveals.

How the Survey Works

The NHIS is an annual survey primarily conducted through face-to-face interviews in respondents’ homes. Telephone interviews are used as a substitute in cases where travel is impractical. For each family interviewed, one child aged 3-17 is randomly selected for the survey through a computer program. Over the four years studied (2018-2021), a total of 26,422 households with children or adolescents participated.

Overall ADHD Prevalence and Age-Related Trends

The analysis found that 9.5% of children and adolescents in the United States had been diagnosed with ADHD, based on reports from family members. However, the prevalence varied significantly with age:

  • Ages 3-5: 1.5%
  • Ages 6-11: 9.6%
  • Ages 12-17: 13.4%

The increase in ADHD diagnosis with age underscores the importance of monitoring children’s developmental needs as they progress through school and adolescence.

Gender Differences: Higher Rates Among Males

The survey revealed a notable difference in ADHD prevalence between genders, with 12.4% of males diagnosed compared to 6.6% of females—nearly a two-to-one gap. This aligns with previous research indicating that ADHD is more frequently diagnosed in boys than girls, though awareness of how ADHD presents differently across genders is growing.

Family Income and ADHD Rates

Family income played a significant role in ADHD prevalence, particularly among lower-income groups:

  • Below the poverty line: 12.7%
  • Above the poverty line but less than twice that level: 10.3%
  • Above twice the poverty level: 8.5%

This pattern suggests that socioeconomic factors might influence the diagnosis and management of ADHD, with lower-income families possibly experiencing greater barriers to early diagnosis or consistent treatment.

Regional Differences Across the U.S.

Geographic location also impacted ADHD rates. Prevalence was highest in the South (11.3%), followed by the Midwest (10%), the Northeast (9.1%), and significantly lower in the West (6.9%). These variations could reflect regional differences in healthcare access, diagnostic practices, or cultural attitudes towards ADHD.

Stability Over Time

Despite these variations in demographics, the overall prevalence of ADHD remained relatively stable across the study period from 2018 to 2021, showing no significant changes by year.

What This Means for Families and Healthcare Providers

The findings from this updated analysis provide a clearer picture of ADHD’s prevalence across different demographic groups in the United States. They highlight the need for tailored approaches to diagnosis and care, taking into account factors like age, gender, income, and geographic location. With ADHD being a common condition affecting nearly 1 in 10 children, ongoing research and support for families are crucial to ensure that those with ADHD receive the care and resources they need.

Conclusion: 

This study reinforces the importance of awareness and early intervention, especially for families in underserved regions or those facing economic challenges. As clinicians and educators continue to support children with ADHD, understanding these demographic trends can help in creating more equitable access to diagnosis and treatment.

October 29, 2024

Meta-Analysis Shows No Significant Impact of Caffeine on ADHD Symptoms

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 Search for Evidence: A Limited Pool of Studies

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.

Findings: Minimal Impact, No Statistical Significance

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.

Conclusion: Caffeine Is Not a Substitute for ADHD Medications

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.

October 28, 2024

ADHD’s Impact on Criminal Convictions—and How Medication Reduces Risk

Swedish Study Reveals ADHD’s Impact on Criminal Convictions—and How Medication Reduces Risk

ADHD has long been associated with higher rates of criminal behavior, but most studies have relied heavily on self-reported data and small, non-representative samples. A new Swedish study addresses these limitations, providing a more comprehensive and reliable picture using data from nationwide registers. It sheds light on the role of ADHD medication in reducing the risk of criminal convictions, offering insights for clinicians, policymakers, and families.

Previous Research: The Denmark Comparison

Earlier research, such as a 2019 Danish study, found that ADHD diagnosed in children and adolescents ages 4 to 15 was associated with a 1.6-fold increased risk of future criminal conviction. However, these findings were limited by a smaller sample size and a focus on just one nation’s context. Like Denmark, Sweden’s single-payer universal healthcare system allows for the collection of extensive data on health and crime records, providing an ideal environment for large-scale, population-based research.

Swedish Study Design: A Robust Approach

To investigate ADHD’s connection to criminal behavior, the Swedish research team analyzed records from a cohort of 1,646,645 individuals born between 1986 and 1997. They excluded those who died or emigrated before age 15 (the age of criminal responsibility in Sweden) and those who immigrated to Sweden, resulting in a final study group of 1,235,939 individuals. Slightly more than half of the cohort was male.

ADHD diagnoses were based on clinical records and prescriptions for approved ADHD medications, while criminal convictions—both violent and nonviolent—were identified using Sweden’s National Crime Register, covering the years 2001 to 2013. The study adjusted for various potential confounding factors, including sex, birth year, parental education, and other psychiatric conditions. They also used the Swedish Multi-Generation Register to control for unmeasured familial factors to compare outcomes among full siblings.

Key Findings: ADHD and Criminality

The study found that ADHD is strongly associated with increased rates of criminal convictions. Compared to individuals without ADHD, those with an ADHD diagnosis were roughly:

  • Four times more likely to be convicted of a violent crime.
  • Twice as likely to be convicted of a nonviolent crime.

Interestingly, when comparing conviction rates among males and females with ADHD, the rates of nonviolent convictions were similar, but females with ADHD were about 25% more likely to be convicted of a violent crime than males with ADHD.

The Role of Medication: A Significant Moderating Factor

The research also highlighted the importance of ADHD medication in reducing criminal behavior. When individuals with ADHD who were taking medication were excluded from the analysis, the data showed significantly higher rates of criminal convictions:

  • Unmedicated males with ADHD had a 50% higher rate of violent convictions and more than double the rate of nonviolent convictions compared to their typically developing peers.
  • Unmedicated females with ADHD faced even greater risks, with nearly triple the rate of violent convictions and quadruple the rate of nonviolent convictions.

These findings suggest that ADHD medications can significantly reduce the risk of both violent and nonviolent criminal behavior in individuals with ADHD, emphasizing the value of pharmacological treatment for those with the condition.

Clinical Implications: Medication as a Risk-Reducing Strategy

The researchers concluded that “ADHD is a strong risk factor for both violent and non‐violent criminal convictions in males and females even after adjustments for psychiatric comorbidities and unmeasured familial factors.” The study also found that untreated ADHD poses a particularly high risk for criminal behavior, highlighting the protective role of medication.

These findings are clinically relevant for several reasons. First, they reinforce the importance of ensuring that individuals with ADHD have access to effective treatment options, especially during the transition from adolescence into adulthood, which is statistically a period of higher risk for criminal behavior. Additionally, the study provides critical data for shaping public policy and interventions aimed at supporting individuals with ADHD, with a focus on reducing criminality through proper management of the disorder.

Conclusion:

This study offers new insights into the complex relationship between ADHD, medication, and criminal behavior, emphasizing the crucial role of treatment in mitigating risks. It provides a compelling case for prioritizing access to ADHD medication as part of a broader strategy for supporting those with ADHD.