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A meta-analysis of eight studies with a combined total of over 396,000 persons with ADHD reported a twofold greater risk of premature death in persons with ADHD as compared with the general population. There was no significant difference in mortality between males and females with ADHD.

But when natural causes of death, primarily disease, were distinguished from unnatural causes, such as injuries and poisoning, virtually all the increased risk was attributable to the latter.

A meta-analysis of four studies with a combined total of over 394,000 participants with ADHD found no significant increase in natural mortality among persons with ADHD. This held for both males and females.

But a meta-analysis of ten studies with over 430,000 persons with ADHD found a nearly threefold increase in unnatural mortality (injuries, poisoning, etc.) in persons with ADHD. Among females (five studies, over 110,000 participants) the increase was threefold. Males with ADHD (five studies, over 310,000 participants) were 2.5 times more susceptible to premature death.

An important caution: in all of these meta-analyses, between-study heterogeneity was extreme, meaning there was little consistency from one study to the next. Moreover, no effort was made to evaluate the likelihood of publication bias.

The largest study, with over 275,000 participants with ADHD, found a negligible and only marginally significant 7% increased all-cause risk of death. It found no increase in natural causes of mortality, but a 50% increase in unnatural causes of premature mortality.

The authors described these results as "suggestive," but emphasized that "the evidence was judged as only low confidence," in line with "inconsistent" evidence from previous nationwide population studies: in Denmark, a twofold increase in all-cause mortality; in Sweden, a fourfold increase; but in Taiwan, a tiny 7% increase that was at the limit of statistical significance, once the data was fully adjusted for confounding factors.

That led the authors to suggest "that all relevant potential confounders should be accounted for" in "future studies."

Bipolar disorder is a severe mental illness that afflicts over one in fifty persons worldwide. About a quarter of those with bipolar disorder also has alcohol use disorder (AUD). This in turn complicates the treatment of their bipolar disorder. It exacerbates their symptoms, makes them more likely to be suicidal, and increases the risk of hospitalization.

More than one in five persons with bipolar disorder also have ADHD, which is likewise known to be correlated with AUD. To what extent does ADHD contribute to AUD in persons with comorbid bipolar disorder?

A European study team recently conducted a systematic search of the peer-reviewed medical literature to address that question. The team identified eleven studies with a combined total of 2,734 participants that could be aggregated to perform a meta-analysis.

They found that persons with comorbid ADHD and bipolar disorder were two and a half times more likely to be diagnosed with alcohol use disorder than persons with bipolar disorder but no ADHD.

Between-study heterogeneity was negligible, and there was no sign of publication bias.

The authors concluded, "At least a portion of the high rates of AUD in BD may, thereby, be related to comorbid ADHD. Longitudinal studies are needed to clarify the nature of this relationship."

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."

ADHD is known to be associated with cognitive impairments, including diminished ability to inhibit risky behavior patterns and diminished attentiveness. Studies have shown that youths with ADHD have higher rates of injury in general, and are more likely to be hospitalized. Burn injuries requiring medical attention are not only serious in themselves but often lead to ongoing psychological trauma.

Taiwan launched a single-payer health care system in 1995. It covers 99.5 percent of the population, ensuring that its database covers virtually the entire population.

A previous study using the national health Insurance Research Database reported a 60 percent increase in the risk of burn injury among youths with ADHD, but it excluded youths under six years old.

So another Taiwanese team of researchers returned to the database and identified all 52,705 youths under 18 with a diagnosis of ADHD between 1996 and 2013 and o prior burn injury, and matched them with an equal number of age-, sex-, and other comorbidity-matched controls.

The control and ADHD groups were matched using one-to-one propensity score matching, determined using multivariate logistic regression analysis with sex, age, urbanization level of the residence, and comorbidities. Comorbidities addressed in this way included seizures, intellectual disability, autism, conduct disorder, oppositional defiant disorder, anxiety, and depression.

The rate of burn injury in the ADHD group was 4.6 percent, versus 2.6 percent in the matched control group. Overall, youths with ADHD were over 75 percent more likely to suffer burn injuries than matched controls. For children under six years old, the risk for those with ADHD was double the risk for controls. For youths with ADHD from six to seventeen years old, the risk was about 70 percent greater than for controls. There were no significant sex differences.

The authors speculated that "The correlation between ADHD and burn injury has several potential explanations. Impulsive behavior is believed to play a major role in burn injuries. ... Additionally, carelessness related to attention deficit, overlooking danger, and impairments in motor coordination and executive function may be associated with burn injuries. However, limited attention has been paid to these possible mediating factors. A further comprehensive examination of the causal relationship between ADHD and burn injury is warranted."

They concluded, "Our findings indicate that individuals with ADHD and who were aged younger than 6 years were at higher risk of burn injury. These higher numbers of burns in early childhood may be linked to the inquisitive behavior of children who have not acquired sufficient experience regarding dangers, as well as their total dependency on parents and caregivers... The results of this study suggest that clinicians pay attention to burn risk for patients with ADHD, particularly for children aged younger than 6 years."