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March 1, 2022
Boys are three times as likely as girls to be diagnosed with ADHD, and anywhere from three to sixteen times more likely to be referred for treatment.
An international team of experts recently published a consensus statement addressing this discrepancy and offering guidance to rectify the imbalance and improve diagnosis and care for girls and women with ADHD. Here are some key conclusions.
ADHD symptoms:
-Experts caution that ADHD behaviors typically express themselves differently in boys than in girls.
-That in turn leads to gender-based biases in teachers and parents. In two studies in which teachers were shown vignettes of individuals with typical ADHD behaviors, switching from female to male names and pronouns led to higher rates of referral for support and treatment.
Comorbidity:
-A major reason for this different expression of ADHD in boys is that they have much higher rates of comorbid externalizing disorders, such as the conduct disorder and oppositional defiant disorder, leading them to break rules and get into fights in school. This no doubt contributes to lower rates of referral for girls.
-On the other hand, females are more likely to have comorbid internalizing disorders, such as emotional problems, anxiety, and depression. These may be interpreted as primary conditions, and the link to ADHD is missed altogether.
-Because ADHD has come to be associated with many externalizing disorders, it is then easy to fail to identify it when it is associated with internalizing disorders such as eating disorders.
-Untreated ADHD in girls can increase the risk of substance use disorders.
Associated vulnerabilities:
Children with ADHD are more likely to be unpopular with their peers and to experience rejection. Whereas boys are more likely to experience that rejection in physical ways, girls are more likely to experience it in social ways and through cyberbullying. That, in turn, contributes to lower self-esteem, which could explain some comorbid internalizing disorders.
Symptoms of hyperactivity/impulsivity, one of the two key components of ADHD, are associated with higher rates of risk-taking behavior:
- Like males with ADHD, females with ADHD have higher injury rates.
-Both males and females with ADHD are more likely to underachieve in school or drop out altogether.
-Overall, adolescents with ADHD become sexually active earlier, have more sexual partners, and are more frequently treated for sexually transmitted diseases than their normally developing peers. That also leads to higher rates of teenage and unplanned pregnancies.
-As with males with ADHD, females with ADHD have higher rates of criminal behavior than normally developing peers. While females with ADHD are still half as likely to be convicted of a crime than males with ADHD, one study showed they nevertheless are eighteen times more likely to be convicted of a crime than normally developing females.
Compensatory or coping behaviors:
- Girls may turn to drink alcohol, smoking cannabis, smoking cigarettes, or vaping nicotine to cope with emotional anguish, social isolation, and rejection.
-Some girls may seek to build social support through high-risk activities such as joining a gang, becoming promiscuous, and engaging in criminal behavior.
Triggers for possible referral
Ages 5-11:
-Bedwetting, nail-biting
Ages 5-16:
-Early sexualized behavior
Ages 5-18:
-Suspensions, expulsions, frequent detentions
-Poor attendance/truancy
-Consistent lateness, poor organization
-Academic difficulties, low academic self-esteem
-Conduct problems, conflicts with parents and peers
-Bullying (usually as victims)
-Regular tobacco and alcohol use
- Obesity and other eating disorders
- Repeated injuries
- Sleep difficulties
- Executive function difficulties
- Extreme emotional meltdowns
Ages 12 and above:
- Relationship problems, anxiety about relationships
- Social rejection, isolation
- Substance abuse, including alcohol
- Risky sexual behavior
- Underage or unwanted pregnancy
- Delinquency or criminal behavior (including shoplifting, vandalism)
- Low self-esteem
- Self-harm, suicidality
Ages 16 and above:
- Dropping out of school
- Losing jobs
- Parenting problems
- Criminality
- Financial difficulties
- Traffic crashes
- Internalizing conditions: depression, anxiety
Ages 18 and above:
- Gambling problems, compulsive shopping
- Personality disorder
- Chronic fatigue syndrome
- Fibromyalgia
The key message is not to disregard females because they do not present with the externalizing behavioral problems, or the disruptive, hard-to-manage boisterous, or loud behaviors typically associated with males with ADHD.
Diagnosis
The authors emphasize that "comprehensive assessment should be completed to accurately capture the symptoms of ADHD across multiple settings, their persistence over time, and associated functional impairments. High rates of comorbidity are typically present. The assessment process is typically tripartite, involving the use of rating scales, a clinical interview, and ideally objective information from informants or school reports."
Rating scales: Ideally rely on those that provide female norms, making them more sensitive to female presentation.
Clinical interviews:
-Be mindful of age-appropriate, common-occurring conditions in females with ADHD, including autistic spectrum disorder, tics, mood disorders, anxiety, eating disorders, fibromyalgia, and chronic fatigue syndrome.
- Be alert to signs of self-harming behaviors(especially cutting), which peak in adolescence and early adulthood.
-Given that heritability of ADHD is high, ranging between 70-80% in both children and adults, be mindful that informants who are family members may also have ADHD (possibly undiagnosed) which may affect their judgment of "typical" behavior. The assessor should obtain specific examples of behavior from the informant and use these to make clinically informed judgments, rather than relying upon the informants' perception of what is typical or atypical.
Treatment
Pharmacological:
- Recommendations for medication do not differ by sex, except that pharmacological treatment is generally not advised during pregnancy or breastfeeding.
- A systematic review and network meta-analysis recommended methylphenidate for children and adolescents and amphetamines for adults, taking into account both efficacy and safety. Larger confidence intervals about the tolerability and efficacy of bupropion, clonidine, and guanine were reported, indicating less conclusive results about the efficacy and tolerability of these oral medications. The use of medication should be followed up over time to verify if medications are effective and well-tolerated, and to manage the effects of related conditions(e.g. anxiety, depression) if they emerge.
Non-pharmacological:
- Cognitive behavioral therapy (CBT) together with psychoeducation (which can be provided to both patients and parent/guardians together or independently) are the best forms of psychological treatment.
- Parents and other guardians of teenage girls need to be shown how to identify deliberate self-harming or risky behavior.
- Adolescent girls may require assistance in addressing risky behavior (sexual risk, substance misuse) and improving self-management. Girls with ADHD are more vulnerable to sexual exploitation and have higher rates of early and unwanted pregnancy.
- Adults are more likely to require interventions to address employment problems, child-rearing, and parenting. Women with ADHD are also more vulnerable to sexual exploitation, including physical and sexual violence.
- Interventions should support attendance and engagement with education to avoid early school-leaving, diminished educational attainment, and associated vulnerabilities. While externalizing conditions have a greater impact on classroom behavior, internalizing conditions affect motivation and thus the ability to benefit from education.
Institutional outreach
- Educational, social care, occupational, and criminal justice system professionals should be trained to improve the detection and referral of ADHD in girls and women.
- Flexible learning systems and support with childcare can help women with ADHD return to education after having a baby.
- Depending on the country of residence, women who disclose their disability to their employer may be entitled to reasonable adjustments to the workplace to accommodate their condition.
- Low to no-cost apps are available to assist persons with ADHD with itineraries, lists, and reminders.
- Career planning should take into account that some occupations may provide a better fit for women with ADHD: "some individuals with ADHD show a preference for more stimulating environments, active, hands-on, or busy and fast-paced jobs."
- Persons with ADHD, both male and female, make up roughly a quarter of the prison population: "Evidence indicates that ADHD treatment is associated with reduced rates of criminality, is tolerated and effective in prison inmates, and improves their quality of life and cognitive function. This has led to speculation that effective identification and treatment of ADHD may help to reduce re-offending."
The authors concluded, "To facilitate identification, it is important to move away from the previously predominating disruptive boy stereotype of ADHD and understand the more subtle and internalized presentation that predominates in girls and women."
Susan Young, Nicoletta Adamo, BryndísBjörkÁsgeirsdóttir, Polly Branney, Michelle Beckett, William Colley, Sally Cubbin, Quinton Deeley, Emad Farrag, Gisli Gudjonsson, Peter Hill, JackHollingdale, OzgeKilic, Tony Lloyd, Peter Mason, Eleni Paliokosta, Sri Perecherla, Jane Sedgwick, Caroline Skirrow, Kevin Tierney, Kobus van Rensburg, EmmaWoodhouse, “Females with ADHD: An expert consensus statement taking a lifespan approach guiding the identification and treatment of attention-deficit/ hyperactivity disorder in girls and women,” BMC Psychiatry(2020)20:404,https://doi.org/10.1186/s12888-020-02707-9.
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 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 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 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.
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.
To understand why centanafadine is unique among medications for ADHD, it helps to look at how ADHD brain chemistry works:
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:
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:
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:
Common Side Effects:
Other Warnings:
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.
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:
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:
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.
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