May 15, 2021

Myths About The Treatment of ADHD

Myth:  ADHD medications "anesthetize" ADHD children.
 
The idea here is that the drug treatment of ADHD is no more than a chemical straightjacket intended to control a child's behavior to be less bothersome to parents and teachers. After all, everyone knows that if you shoot up a person with tranquilizers, they will calm down.

Fact:  ADHD medications are neither anesthetics nor tranquilizers.

The truth of the matter is that most ADHD medications are stimulants. They don't anesthetize the brain; they stimulate it. By speeding up the transmission of dopamine signals in the brain, ADHD medications improve brain functioning, which in turn leads to an increased ability to pay attention and control behavior.  The non-stimulant medications improve signaling by norepinephrine. They also improve the brain's ability to process signals. They are not sedatives or anesthetics. When taking their medication, ADHD patients can focus and control their behavior to be more effective in school, work, and relationships.  They are not "drugged" into submission.

Myth: ADHD medications cause drug and alcohol abuse
We know from many long-term studies of ADHD children that when they reach adolescence and adulthood, they are at high risk for alcohol and drug use disorders. Because of this fact, some media reports have implied that their drug use was caused by treatment of their ADHD with stimulant medications.

Fact: ADHD medications do not cause drug and alcohol abuse
Some ADHD medications indeed use the same chemicals that are found in street drugs, such as amphetamine.  But there is a very big difference between these medications and street drugs. When street drugs are injected or snorted, they can lead to addiction, but when they are taken in pill form as prescribed by a doctor, they do not cause addiction. When my colleagues and I examined the world literature on this topic, we found that rather than causing drug and alcohol abuse, stimulant medicine protected ADHD children from these problems later in life. One study from researchers at Harvard University and the Massachusetts General Hospital found that the drug treatment of ADHD reduced the risk for illicit drug use by84 a percent. These findings make intuitive sense. These medicines reduce the symptoms of the disorder that lead to illicit drug use. For example, an impulsive ADHD teenager who acts without thinking is much more likely to use drugs than an ADHD teen whose symptoms are controlled by medical drug treatment. After we published our study, other work appeared. Some of these studies did not agree that ADHD medications protected ADHD people from drug abuse, but they did not find that they caused drug abuse.

Myth:  Psychological or behavioral therapies should be tried before medication.  
Many people are cautious about taking medications, and that caution is even stronger when parents consider treatment options for their children.  Because medications can have side effects, shouldn't people with ADHD try to talk therapy before taking medicine?

Fact:  Treatment guidelines suggest that medication is the first-line treatment.
The problem with trying talk or behavior therapy before medication is that medication works much better.  For ADHD adults, one type of talk therapy(cognitive behavioral therapy) is recommended, but only when the patient is also taking medication.  The multimodal treatment of ADHD (MTA) study examined this issue in ADHD children from several academic medical centers in the United States. That study found that treating ADHD with medication was better than treating it with behavior therapy. Importantly, behavior therapy plus medication was no more effective than medication alone. That is why treatment guidelines from the American Academy of Pediatrics and the American Academy of Children and Adolescents recommend medicine as a first-line treatment for ADHD, except for preschool children. ADHD medications indeed have side effects, but these are usually mild and typically do not interfere with treatment.  And don't forget about the risks that a patient faces when they do not use medications for ADHD.  These untreated patients are at risk for worsening ADHD symptoms and complications.

Myth: Brain abnormalities of ADHD patients are caused by psychiatric medications
A large scientific literature shows that ADHD people have subtle problems with the structure and function of their brains.  Scientists believe that these problems are the cause of ADHD symptoms. Critics of ADHD claim that these brain problems are caused by the medications used to treat ADHD.  Who is right?

Fact: Brain abnormalities are found in never medicated ADHD patients.
Alan Zametkin, a scientist at the US National Institute of Mental Health, was the first to show brain abnormalities in ADHD patients who had never been treated for their ADHD.  He found that some parts of the brains of ADHD patients were underactive. His findings could not be due to medication because the patients had never been medicated. Since his study, many other researchers have used neuroimaging to examine the brains of ADHD patients. This work confirmed Dr. Zametkin’s observation of abnormal brain findings in unmediated patients. Reviews of the brain imaging literature have concluded that the brain abnormalities seen in ADHD cannot be attributed to ADHD medications.

Wilens, T., Faraone, S. V.,Biederman, J. &Gunawardene, S. (2003). Does Stimulant Therapy of Attention-Deficit hyperactivity disorder Beget Later Substance Abuse?  Aneta-Analytic Review of the Literature.Pediatrics111, 179-185.
Humphreys, K. L., Eng, T. &Lee, S. S.
(2013).Stimulant Medication and Substance Use Outcomes: A Meta-analysis. JAMA psychiatry, 1-9.
Chang, Z., Lichtenstein, P., Halldner,L., D'Onofrio, B., Serlachius, E., Fazel, S., Langstrom, N. & Larsson, H.
(2014). Stimulant ADHD medication and risk for substance abuse. J Child Psychol Psychiatry55,878-85.
Nakao, T., Radua, J., Rubia, K. &Mataix-Cols, D.
(2011 ). Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication. Am J Psychiatry168, 1154-63.
Rubia, K., Alegria, A. A., Cubillo, A. I., Smith, A. B., Brammer, M.J. &Radua, J.
(2014). Effects of stimulants on brain function inattention-deficit/hyperactivity disorder: a systematic review and meta-analysis. Biol Psychiatry76, 616-28.
Spencer, T. J., Brown, A., Seidman, L. J., Valera, E. M., Makris, N., Lomedico, A., Faraone, S. V. &Biederman,J.
(2013).Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies. J Clin Psychiatry74, 902-17.

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French Cohort Study: Does Methylphenidate Increase Risk of Mania in Patients with Comorbid BP and ADHD?

The Background:

Methylphenidate is an effective treatment for ADHD in adults who also have bipolar disorder (BD), but it carries a potential risk of triggering manic episodes. Current guidelines therefore recommend using it only alongside mood-stabilizing medication. A new study using French nationwide claims data sought to test and extend those recommendations with greater statistical power than previous research. 

The Study:

The study built on findings by Viktorin et al. (2017), who observed that adults with BD not taking mood stabilizers had more than a sixfold higher risk of manic events (defined as hospitalization for mania or a new antimanic prescription) within six months of starting methylphenidate. Patients on mood-stabilizing treatment, by contrast, showed nearly half the baseline risk in the first three months. Those findings were limited, however, by small event counts (fewer than 61 manic episodes) and an effect that did not persist beyond the initial three-month window. 

To build on this, researchers drew on the French National Health Data System (which is a claims database covering more than 60 million people) spanning 2008 to 2024. The final sample included 6,022 adults with BD (56% women) who had started methylphenidate. Using a self-controlled design, the study compared each patient's rate of manic events in the six months before their first methylphenidate prescription with the rate in the six months after, effectively eliminating stable individual differences as a confound. 

Patients were classified as receiving continuous mood-stabilizing treatment if they had been dispensed at least two courses of specific antipsychotics (aripiprazole, olanzapine, or quetiapine) or mood stabilizers (lithium or valproate) in the nine months before starting methylphenidate, including at least one dispensation in the final six months of that window. 

The Results:

The results largely confirmed the earlier findings. Among the 2,745 patients not on mood stabilizers, the rate of inpatient mania diagnosis was 5.1 times higher in the first three months after starting methylphenidate, though this elevation fell to a non-significant level over the subsequent three months. Patients receiving continuous mood-stabilizing treatment showed no statistically significant change in mania risk across the full six-month post-initiation period. A formulation-specific pattern also emerged: patients without mood-stabilizing treatment had a 2.5-fold higher risk associated with extended-release methylphenidate, while no significant risk increase was seen with the immediate-release formulation or in treated patients regardless of formulation. 

The Conclusion:

The authors conclude that methylphenidate at doses below 30 mg does not appear to elevate manic relapse risk when prescribed alongside mood stabilizers. The elevated risk seen in untreated patients, particularly with extended-release formulations, must be interpreted cautiously, given limited statistical power and the likelihood that it partly reflects the natural fluctuation of manic relapse over time. The authors flag this as an inherent limitation of self-controlled survival analyses when studying drug-induced mania, where temporal trends in the underlying condition can be difficult to disentangle from treatment effects. 

A New ADHD Medication That Works Differently in the Brain

The FDA has approved a new once-daily pill called centanafadine (trade name SIMTRIYO®). Approved for adults and kids aged 6 and older (weighing at least 44 lbs / 20 kg), centanafadine is a new category of ADHD treatment that aims to give fast results with fewer of the downsides of traditional stimulants.

What Makes This Drug Different?

To understand why centanafadine is unique among medications for ADHD, it helps to look at how ADHD brain chemistry works:

  1. Norepinephrine: Powers focus, alertness, and attention span.
  1. Dopamine: Drives motivation, reward system, and decision-making.
  1. Serotonin: Regulates mood, anxiety levels, and emotional stability.

Stimulants like Ritalin and Adderall work mainly in the dopamine system.  Nonstimulants like atomoxetine, viloxazine, clonidine and guanfacine work mainly on the norepinephrine system.  Centanafadine is the first drug in a new class called NDSRIs (Norepinephrine, Dopamine, and Serotonin Reuptake Inhibitors). We can describe its effects as follows:

  • Heavy boost to Norepinephrine: Delivers the strong focus and attention boost you need.
  • Moderate, smooth increase to Dopamine: Helps with motivation and brain executive function without triggering massive dopamine spikes that lead to addiction or heavy crashes.
  • Moderate boost to Serotonin: Helps smooth out mood swings and keeps anxiety under control.

What Did Clinical Trials Show?

The FDA approved centanafadine based on studies involving thousands of adults, teens, and children. Here are the key findings:

Centanafadine showed some improvement in ADHD symptoms within the very first week of taking it although a full effect takes about six weeks.

In adult trials, taking 200 mg or 400 mg daily led to significant improvements in real-world skills:

  • Time management and prioritizing tasks
  • Starting projects without procrastinating
  • Planning complex tasks and staying organized
  • Short-term working memory

In trials with children (ages 6–12) and teens (ages 13–17), centanafadine significantly reduced core ADHD symptoms like hyperactivity, impulsivity, and lack of focus compared to a placebo.

About 30% to 40% of adults with ADHD also suffer from anxiety. Traditional stimulants can make anxiety worse. In a trial specifically designed for adults dealing with both ADHD and anxiety, centanafadine effectively treated ADHD symptoms without firing up their anxiety, which might be due to its serotonin boost.

Does Centanafadine have Side Effects?

While Centanafadine was well-tolerated by most people in studies, like any prescription medication, it comes with important safety guidelines.

Prescribing Warnings:

  • Suicidal Thoughts in Children: In trials for kids aged 6 to 12, centanafadine was linked to a higher risk of suicidal thoughts and behaviors compared to a sugar pill.  Although rare, parents and doctors should look for changes in mood or behavior, especially when starting or changing doses.
  • Stimulant Classification: Because it acts on central nervous system pathways, especially dopamine, centanafadine is classified as a CNS stimulant so might lead to addiction. While it has a much lower abuse risk than stimulants like Ritalin or Adderall, doctors should still evaluate patients for any history of substance abuse before prescribing.

Common Side Effects:

  • Kids & Teens: Decreased appetite, stomach ache, nausea, rash, and headache.
  • Adults: Dry mouth, difficulty sleeping (insomnia), decreased appetite, nausea, and headaches.

Other Warnings:

  • Heart & Blood Pressure: It can cause small increases in heart rate and blood pressure, so doctors will check these regularly.
  • Drug Interactions: It cannot be taken with certain antidepressants (MAOIs) due to dangerous blood pressure risks.

The Bottom Line

Overall, centanafadine is a new step forward in how we treat ADHD. Because it acts differently in the brain than traditional treatments, patients who struggle with stimulant-related anxiety or side effects may find it useful to explore with their doctor.

Nitrogen Dioxide Linked to Higher ADHD Risk: Insights from a Massive South Korean Study

A landmark nationwide study from South Korea has uncovered a significant link between prenatal exposure to air pollution — specifically nitrogen dioxide (NO2) — and an increased risk of ADHD in children. 

While researchers have long suspected that air pollutants interfere with fetal brain development through inflammation and oxidative stress, this study is one of the largest and most comprehensive of its kind, following nearly 1.5 million births for up to 13 years. 

Why South Korea? 

South Korea provided a unique countrywide “laboratory” for this research due to two key infrastructure strengths: 

  • Universal Health Data: A national insurance database that tracks the health outcomes of the entire population. 
  • Granular Air Monitoring: A network of 642 monitoring stations that allowed researchers to precisely estimate what pollutants mothers were breathing based on their postal codes. 

Key Findings: The “Smoking Gun” of NO2 

While the study looked at several pollutants, nitrogen dioxide — a byproduct of fossil fuel combustion in cars and power plants — emerged as the primary concern. 

Pollutant 

Association with ADHD Risk 

Nitrogen Dioxide (NO2) 

Strongest Link: Every 1-ppb (part-per-billion) increase in exposure linked to a 22% rise in risk. 

Sulfur Dioxide (SO2) 

Minimal Link: Only a slight 4% increase per ppb. 

Ozone (O3) carbon monoxide (CO), & particulates 

No significant association was found. 

The scale of the NO2 risk is particularly striking. Over the typical range of exposure levels found in the study (an interquartile range of 13 ppb), the data suggest a threefold increase in ADHD risk for children in the highest-exposure groups compared to the lowest. 

Accounting for Other Factors 

To ensure the results weren’t skewed by other variables, the researchers controlled for a wide range of confounders including: 

  • Socioeconomic and employment status. 
  • Maternal age and baseline health. 
  • The child’s sex. 
  • The presence of 14 different medical conditions around childbirth. 

The authors emphasized the strong association between maternal nitrogen dioxide exposure and ADHD, while also noting the small but significant association with sulfur dioxide.  

The Take-Away: A New Frontier for Public Health 

Historically, air quality laws have been designed to protect our lungs and hearts. However, this study adds to a growing body of evidence suggesting that the brain is likewise vulnerable. 

In a commentary on the findings, expert George Ayoub argued that “neurodevelopment should be explicitly considered” when governments perform cost-benefit analyses on air quality regulation.  My view is a bit different.  The association is intriguing but the study does not establish cause and effect.  Many statistically significant environmental risk associations for neurodevelopmental disorders have disappeared after controlling for maternal risk for ADHD.  I hope this research team will do those analyses if feasible.