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The Background: 

Randomized clinical trials have shown ADHD medications are effective in reducing core ADHD symptoms. Moreover, large observational studies indicate that these medications are associated with lower risks of real-world outcomes, including injuries, crime, transport crashes, suicide attempts, and unnatural-cause mortality. 

Sweden’s ADHD medication use has soared. From 2006 to 2020, children’s use rose almost fivefold, and adults' use more than tenfold. This places Sweden among the highest globally in ADHD prescriptions. 

Research indicates that rising prescription rates are due to changes in diagnostic criteria and their interpretation, parental perception, and greater awareness of ADHD, rather than an actual increase in its prevalence. 

Sweden has a single-payer health insurance system that covers virtually its entire population, as well as a system of national registers that link health care records to other population databases.  

The Study:

A research team based in Sweden used that data to explore how the impact of ADHD medication on self-harm, injuries, traffic crashes, and crime has evolved with the dramatic increase in ADHD prescription rates. The team hypothesized that effects would decrease as medications were prescribed to a broader group of patients, including those with fewer impairments and risky behaviors who might not derive as much benefit from pharmacotherapy. 

The team identified all individuals aged 4 to 64 who were prescribed ADHD medication and living in Sweden in the fifteen years from 2006 through 2020. From this base cohort, they selected four specific cohorts for self-harm, unintentional injury, traffic crashes, and crime, consisting of individuals who experienced at least one relevant event during the study period. 

They used a self-controlled case series (SCCS) design to explore the link between ADHD medication use and outcomes. This approach allows individuals to serve as their own controls, accounting for confounders like genetics, socioeconomic status, or other constant characteristics during follow-up. 

A non-treatment period was defined as a gap of 30 days or more between two consecutive treatment periods. To examine the link between ADHD medication use and outcomes, the team divided follow-up time into consecutive periods for each individual. A new period began after a treatment switch. They estimated incidence rate ratios (IRRs) to compare the outcome event rates during medicated periods with non-medicated periods for the same individual. 

The team examined how ADHD medication outcomes varied with prescription prevalence across three periods: 2006-2010, 2011-2015, and 2016-2020, during which ADHD medication use continuously increased. 

The overall cohort encompassed almost a quarter million ADHD medication users: just over 57,000 for 2006-2010, just over 127,000 for 2011-2015, and slightly over 200,000 for 2016-2020. 

The Results:

ADHD medication use was linked to significantly lower rates of all studied outcomes during the study period. However, as prescription rates increased five to tenfold in the population, the strongest association for reduction in self-harm was observed between 2006 to 2010 (23% reduction in incidence rate) and was slightly reduced (below 20%) in the two more recent periods, though this change was not statistically significant.  

On the other hand, there was a significant decreasing trend in the reduction of incidence rate ratios for unintentional injury, with a 13% reduction in incidence rate in 2006-2010 decreasing over the two more recent periods to half that amount, 7%. For traffic crashes, a 29% reduction in incidence rate significantly diminished by more than half, to 13%. For crime, a 27% reduction in incidence rate from medication use significantly declined to 16%. 

When considering methylphenidate prescriptions only, these effects were partially attenuated for crime. A 28% reduction in the incidence rate for crime in 2006-2010 dropped to 19% in the two most recent periods, but the trend was not statistically significant. Nevertheless, there were no significant differences from the results in the larger cohort in any of the other categories.   

The Interpretation:

These outcomes were consistent with the team’s hypothesis. The researchers concluded, “While ADHD medications are consistently associated with reduced risk of serious real-world outcomes, the magnitude of these associations have decreased over time alongside rising prescription rates. This underscores the importance of continuously evaluating medication use in different patient populations.” 

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Febrile seizure (FS) is a type of childhood seizure accompanied by a fever. It is not caused by infection in the central nervous system or other triggers of acute seizures. It is the most common form of childhood seizure, with an occurrence of 2% to 5% in all infants and children between 6 months and 5 years old. 

Noting that “To the best of our knowledge, no systematic synthesis of literature has assessed the nature and magnitude of the association between FS and ADHD,” a Korean research team performed a systematic search of the medical literature followed by meta-analysis to explore any such association. 

Meta-analysis of twelve studies with a combined total of more than 950,000 persons found that childhood febrile seizures were associated with 90% greater odds of subsequent ADHD. Correcting for publication bias reduced this slightly to 80% greater odds of subsequent ADHD. 

Limiting the meta-analysis to the subset of four studies with over 33,000 participants that adjusted for known confounders strengthened the association. Children who had febrile seizures had greater than 2.6-fold greater odds of subsequently developing ADHD. There was no sign of publication bias, but there was substantial divergence in individual study outcomes (heterogeneity). 

Further limiting the meta-analysis to two studies with a combined 654 participants in which clinical ADHD diagnoses were made by specialists – the gold standard – produced the exact same outcome. In this case, heterogeneity dropped to zero. 

The team concluded, “Overall, our systematic review and meta-analysis has shown a significant positive association between childhood FS and later occurrence of ADHD. Our findings add to the growing body of evidence questioning the notion that childhood FS are universally benign. In addition, the results highlight the need for longitudinal studies to better understand the association between FS and ADHD.”  

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ADHD treatment usually involves a combination of medication and behavioral therapy. However, medication can cause side effects, adherence problems, and resistance from patients or caregivers. 

Numerous systematic reviews and meta-analyses have evaluated the effects of non-pharmacological interventions on ADHD. With little research specifically examining game-based interventions for children and adolescents with ADHD or conducting meta-analyses to quantify their treatment effectiveness, a Korean study team performed a systematic search of the peer-reviewed medical literature to do just that.  

The Study: 

To be included, studies had to be randomized controlled trials (RCTs) that involved children and adolescents diagnosed with ADHD. The team excluded RCTs that included participants with psychiatric conditions other than ADHD.  

Eight studies met these standards. Four had a high risk of bias.  

Meta-analysis of four RCTs with a combined total of 481 participants reported no significant improvements in either working memory or inhibition from game-based digital interventions relative to controls. 

Likewise, meta-analysis of three RCTs encompassing 160 children and adolescents found no significant improvement in shifting tasks relative to controls. 

And meta-analysis of two RCTs combining 131 participants reported no significant gains in initiating, planning, organizing, and monitoring abilities, nor in emotional control. 

The only positive results were from two RCTs with only 90 total participants that indicated some improvement in visuospatial short-term memory and visuospatial working memory.  

There was no indication of effect size, because the team used mean differences instead of standardized mean differences.  

Conclusion:

The team concluded, “The meta-analysis revealed that game-based interventions significantly improved cognitive functions: (a) visuospatial short-term memory … and (b) visuospatial working memory … However, effects on behavioral aspects such as inhibition and monitoring … were not statistically significant, suggesting limited behavioral improvement following the interventions.” 

Simply put, the current evidence does not support the effectiveness of game-based interventions in improving behavioral symptoms of ADHD in children and adolescents. The only positive results were from two studies with a small combined sample size, which does not qualify as a genuine meta-analysis. All the other meta-analyses performed with larger sample sizes reported no benefits. 

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Recent research from the Centers for Disease Control and Prevention (CDC) highlights distinct health and social-emotional challenges faced by teens diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD). This study, published in the Journal of Developmental and Behavioral Pediatrics, offers critical insights directly from the teens themselves, providing a unique view often missed when relying solely on parent or clinical reports. 

Researchers analyzed nationally representative data from July 2021 through December 2022, comparing self-reported experiences of teens aged 12 to 17 with and without ADHD. Approximately 10% of teenagers had an ADHD diagnosis, and the findings reveal specific areas where teens with ADHD face notable difficulties. 

Teenagers with ADHD reported significantly higher rates of bullying victimization and struggles in making friends compared to their peers. Surprisingly, they were less likely to report a lack of peer support, suggesting complexities in how they perceive friendships and social networks. The study underscores the importance of directly engaging teens in assessing their social relationships, rather than solely relying on parental perspectives. 

Sleep difficulties emerged as another critical issue for teens with ADHD. About 80% reported problems like difficulty waking up and irregular wake times, markedly higher than their non-ADHD counterparts. Such disruptions can exacerbate attention difficulties and emotional regulation issues, further complicating daily life for these teens. 

Excessive screen time also stood out, with nearly two-thirds of teens with ADHD spending over four hours daily on screens, excluding schoolwork. This high screen usage is concerning, given its potential negative impact on physical and mental health, including sleep quality and social interactions. 

Notably, the study found no significant differences in physical activity levels or concerns about weight between teens with and without ADHD. This finding contrasts with previous studies that have highlighted lower physical activity among children with ADHD, suggesting the need for continued research on how physical activity is measured and encouraged in this population. 

The study’s authors emphasize the importance of health promotion interventions tailored specifically for teens with ADHD. By directly engaging teens and considering their unique perspectives, interventions can better address social-emotional well-being and healthy lifestyle behaviors, ultimately improving long-term outcomes for this vulnerable group. 

Overall, this research provides compelling evidence for healthcare providers, educators, and families to focus on supporting teens with ADHD in areas of social skills, sleep hygiene, and healthy screen time habits. Such targeted support can significantly enhance the quality of life and health outcomes for adolescents navigating the challenges of ADHD. 

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The Background on ADHD Treatments, rTMS and tDCS:

Methylphenidate is known as the gold-standard treatment for ADHD, increasing dopamine concentrations and helping to focus. However, these psychostimulants may be less well-tolerated in adults. Adverse effects include decreased appetite, nausea, racing heartbeat, restlessness, nervousness, and insomnia. 

Neurofeedback is a non-pharmaceutical treatment that combines cognitive behavioral therapy techniques like conditioning and positive reinforcement with electroencephalography (EEG) feedback. Electrodes are placed on specific brain areas, guiding patients to regulate their brainwave activity. 

Repetitive transcranial magnetic stimulation (rTMS) uses electromagnetism to induce an electric field by passing a magnetic field through the scalp. Transcranial direct current stimulation (tDCS), on the other hand, directly applies an electric current through the scalp. Both repetitive transcranial magnetic stimulation (rTMS) and tDCS primarily target the outermost layers of neurons, as they are non-invasive methods. Nevertheless, both techniques are believed to affect deeper layers through interconnected neuronal networks.  

The Study:

A French research team conducted a systematic search of the peer-reviewed medical literature to perform a meta-analysis to explore the efficacy of these experimental treatment techniques. 

Eight studies – four using rTMS and another four using tDCS – met the inclusion criteria. Studies had to be randomized controlled trials (RCTs), and had to involve multiple sessions of treatment. Participants had to be adults previously diagnosed with ADHD.  

Outcomes were measured through self-rated scales, neuropsychological tests, and electrophysiological pre-post evaluations. 

Separate meta-analyses of the four tDCS RCTs combining 154 participants and of the four rTMS RCTs encompassing 149 participants likewise reported no significant improvements. In all cases variation in outcomes between studies was moderate, and there were no signs of publication bias. 

The Conclusion on Neuromechanistic Treatments for ADHD:

Meta-analysis of all eight studies with a combined total of 421 participants reported no significant improvements over controls. Narrowing down to studies that used sham controls likewise produced no significant improvements. So, despite the title of this study, these neuromechanistic treatments do not appear to be the future of treatment for adult ADHD.

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According to the World Health Organization, suicide is the second leading cause of death among individuals aged 15 to 29 years. 

A European study team recently released findings of the first meta-analysis to explore the association between clinically diagnosed ADHD in children and adolescents and subsequent suicidality.  

The criteria for study inclusion were: 

• Most participants had to be under 18 at baseline. 

• Longitudinal design, meaning that participants were followed over time. 

• Having an ADHD sample diagnosed in childhood that was followed up for suicidal behavior. 

• Having a control group without ADHD that was followed up for suicidal behavior. 

• That ADHD was clinically diagnosed based on DSM-5 criteria. 

• The total number of participants and of those with suicidal behavior in both the ADHD group and the control group during follow-up were reported. 

All selected studies scored at least eight out of 11 points after quality assessment. The most frequent defect was that it was unclear whether suicidal behavior had occurred before study initiation. 

Meta-analysis of all nine included studies, encompassing more than 4.4 million participants, reported more than threefold greater odds of overall suicidal behavior among children and adolescents previously diagnosed with ADHD, as opposed to children and adolescents not previously diagnosed with ADHD. Study outcomes varied significantly (high heterogeneity) but showed no publication bias. 

Breaking this down into subcategories of risk: 

• Two studies combining 521 participants reported roughly fourfold greater odds of suicidal ideation among those previously diagnosed with ADHD, with negligible heterogeneity. 

• Six studies encompassing a total of more than 87,000 children and adolescents reported more than threefold greater odds of suicide attempt among those previously diagnosed with ADHD, with high heterogeneity. 

• Two studies combining more than 2.6 million participants reported a near-quadrupling of the odds of suicide death among those previously diagnosed with ADHD, with negligible heterogeneity. 

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The team concluded, “the current systematic review and meta-analysis has confirmed previous findings that there is an elevated risk for suicidal behavior in ADHD patients.” They also note, however, that “this relationship is heterogeneous and complex, with significant differences across ADHD subtypes, age groups, sexes, comorbidities, and social issues, all of which play important roles in the development of suicidal behavior.”

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The Newest Non-stimulant Medication for ADHD

Centanafadine, which is currently under investigation as a treatment for ADHD, will be the first triple reuptake inhibitor for the disorder if it is approved by the FDA. It improves norepinephrine, dopamine and serotonin levels. This new medication is not a stimulant, but due to the dopamine component, it has a stimulant-like effect in patients. In adults, two phase 3 trials and a year-long extension have shown sustained benefits and a tolerable safety profile, laying the groundwork for pediatric research.

Based on this study, improvement was already noticeable after the first week and held steady through week 6. The lower dose (164.4 mg) didn’t separate from placebo, reminding us that getting the dose right will be critical. The effect size was smaller than what is seen for stimulants but 50% of patients had excellent outcomes as indicated by reductions in the ADHD-RS of 50% or more.

Side effect patterns look familiar to anyone who prescribes ADHD medications; loss of appetite, nausea and headaches topped the list. About half of teens on the higher dose reported at least one treatment-emergent adverse event, compared with a quarter of those on placebo. Severe reactions were rare but did include isolated liver enzyme spikes, rash, and a few reports of aggression or somnolence. For everyday practice, that translates to routine growth checks, a look at baseline liver function, and clear guidance to families about reporting rashes or mood changes promptly.

The researchers noted that the study had certain limitations, including limited generalizability to adolescents beyond North America, the exclusion of teacher ratings on the ADHD-RS-5 scale and the study’s short duration. They added that future studies should explore long-term treatment outcomes and efficacy compared with other ADHD treatments, as well as its effect on treating ADHD with comorbid conditions.

Why should this matter to clinicians already juggling multiple non-stimulant options for ADHD?

First, speed. Centanafadine separated from placebo within a week. In this regard, it might be closer to stimulants than to the multi-week ramp-up we expect from current non-stimulants. Second, it offers another option when stimulants are contraindicated or poorly tolerated, or when they raise diversion concerns. Its mechanism also makes it intriguing for patients who need both norepinephrine and dopamine coverage but prefer to avoid schedule II drugs. Because it also improves serotonergic transmission, it may be useful for some of ADHD’s comorbidities (see our new article for evidence about serotonin’s role in these disorders).

Keep in mind that centanafadine for ADHD is still investigational, so participation in clinical trials remains the only access route.

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A recent in-depth clinical review published by the American Academy of Neurology examines how ADHD manifests in adulthood and how neurologists can differentiate it from other causes of attention problems. 

Recognition of ADHD in adults by clinicians is often delayed or misdiagnosed due to overlapping symptoms with anxiety, depression, sleep disorders, and life stressors. Conversely, as ADHD in adults becomes more widely acknowledged, largely due to increased public awareness and social media trends, clinicians need to take extra care not to incorrectly diagnose patients with ADHD. This publication aims to shine a light on both sides of this issue and highlight the importance of clinicians being trained in proper ADHD screening. 

ADHD Symptom Overlaps and Differential Diagnosis 

The article highlights how many adults come to neurology clinics convinced they have ADHD after online quizzes or watching others get diagnosed. True ADHD must be differentiated from issues with shared signs and symptoms such as poor sleep, anxiety, depression, or even OCD or Bipolar Disorder. This is a high-level clinical skill called differential diagnosis.

• Sleep Issues- This is one of the most common causes of attention and focus problems that resemble ADHD in adults. Chronic sleep deprivation can lead to issues like distractibility, forgetfulness, and emotional instability, which may be mistaken for ADHD symptoms, especially if people don’t realize how long-term sleep loss has affected them. Clinicians are encouraged to ask about sleep habits and use tools like the Epworth Sleepiness Scale.

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• Anxiety Disorders- Anxiety is common in adults with ADHD, but a patient with anxiety who does not have ADHD may present with signs and symptoms that overlap with ADHD. A key difference between anxiety and ADHD is that people with ADHD often get distracted even when relaxed or doing something enjoyable without realizing it. Those with anxiety usually feel tense, guilty, and very aware of their distraction.

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• Depression- Depression can cause trouble with focus, energy, and motivation, again, often overlapping with or mimicking symptoms of ADHD. Since both conditions are common, they can also occur together, making it important to look at when symptoms started. If attention problems were present before any depressive episodes, it may point to ADHD, but in unclear cases, treating depression first and then reassessing can help clarify the diagnosis.

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• OCD- Some people with ADHD experience distressing, repetitive thoughts that feel like OCD, even if they haven’t been diagnosed with it. These thoughts can cause anxiety or sadness, even when the person knows they’re unlikely or irrational, but unlike OCD, there are no compulsive behaviors. In some cases, ADHD medication helps reduce these thoughts by improving focus and emotional regulation.

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• Autism- Adults with ASD are more likely to also have ADHD, and in some cases, ADHD symptoms, such as missing social cues or acting impulsively, can be mistaken for autism. This overlap can sometimes make diagnosis more complicated.

The author of the article, Dr. Mierau, provides detailed clinical strategies such as asking open-ended questions, exploring how symptoms show up at home and at work, and watching for patterns like chronic lateness or emotional overeating. (This paper points out that, while not included in the DSM-VI, food cravings and binge behaviors are commonly found in patients with ADHD.)

This review correctly emphasizes that neuropsychological testing is not necessary for diagnosis. Instead, a thorough clinical interview, including a detailed family history and behavioral observation, can be more telling. 

Conclusion: Real Barriers to Proper ADHD Diagnosis

The review article closes with a call to action: the biggest obstacle isn’t diagnosing or treating ADHD, it’s access. Adults struggle with pharmacy shortages, no-refill laws, and insurance hurdles, despite research showing treatment reduces mortality and improves life quality. Dr. Mierau argues for more trained providers, better public education, and policy changes to reduce stigma and expand access.

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New research has uncovered important links between certain blood metabolites and ADHD by using a genetic method called Mendelian randomization. This approach leverages natural genetic differences to help identify which metabolites might actually cause changes in ADHD risk, offering stronger clues than traditional observational studies.

Key Metabolic Pathways Involved:

The study found 42 plasma metabolites with a causal relationship to ADHD. Most fall into two major groups:

• Amino acid metabolites from protein metabolism, including those related to tyrosine, methionine, cysteine, and taurine.
  
  
• Fatty acids, especially long-chain polyunsaturated fatty acids (PUFAs) like DHA and EPA, important for brain function.
  
  

What Does This Mean for Diet and ADHD?

Since many metabolites come from dietary sources like proteins and fats this supports the idea that diet could influence metabolic pathways involved in ADHD. However, because the study focused on genetic influences on metabolite levels, it doesn’t directly prove that dietary changes will have the same effects.

Notable Metabolites:

• 3-Methoxytyramine sulfate (MTS): linked to dopamine metabolism, higher genetic levels of MTS were associated with a lower risk of ADHD. Dopamine plays a crucial role in attention and behavior.
  
  
• DHA and EPA: Omega-3 fatty acids abundant in the brain; higher levels were linked to reduced ADHD risk, supporting existing research on omega-3 supplements.
  
  
• N-acetylneuraminate: Involved in brain development and immune function, with higher levels linked to increased ADHD risk, though more research is needed to understand this.
  
  

Five metabolites showed bidirectional links with ADHD, meaning genetic risk for ADHD also affects their levels which suggests a complex interaction between brain function and metabolism.

Twelve ADHD-related metabolites are targets of existing drugs or supplements, including:

• Acetylcysteine: an antioxidant used in various treatments.
  
  
• DHA supplements: widely used to support brain and heart health.
  
  

What This Study Doesn’t Show

While these findings highlight biological pathways, they don’t prove that changing diet will directly alter ADHD symptoms. Metabolite levels are shaped by genetics plus environment, lifestyle, and health factors, which require further study.

Conclusion: 

This research provides stronger evidence of metabolic pathways involved in ADHD and points to new possibilities for diagnosis and treatment. Future work could explore how diet or drugs might safely adjust these metabolites to help manage ADHD.

While this study strengthens the link between amino acid and fatty acid metabolism and ADHD risk, suggesting that diet could play a role, ultimately more research is still needed before experts could use this research to give specific nutritional advice.

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