New research from the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King's College London has found that the effectiveness of drugs for ADHD may be associated with an individual's neuroanatomy.
The study was published on Nature Mental Health.
The importance of brain maps in ADHD individuals
The research suggests that the development of clinical interventions for ADHD could benefit from identifying how the brain anatomy of treatment-resistant individuals may differ from that of individuals who respond to medications.
Researchers studied individual responses to two months' treatment with methylphenidate (MPH), the prescription drug typically used to treat ADHD, in 60 adults. Using MRI, they compared brain anatomy between neurotypical individuals and controls, and between individuals who responded and those who did not respond to treatment.
Finally, to better understand their findings, they mapped anatomical group differences onto brain maps of genetic expressions.
The researchers found that adults with ADHD who did not respond to MPH had significant differences in brain anatomy compared to both those who responded and controls. These anatomical differences meant that their attention improved less during treatment.
Finally, to better understand their findings, they mapped anatomical group differences onto brain maps of genetic expressions.
The researchers found that adults with ADHD who did not respond to MPH had significant differences in brain anatomy compared to both those who responded and controls. These anatomical differences meant that their attention improved less during treatment.
Some group differences between individuals with ADHD and controls were associated with differences in the expression of genes related to the transport of norepinephrine, a known drug target.
Although MPH is generally effective in improving ADHD symptoms, these findings may help researchers and clinicians understand previous randomized, controlled trials that have reported that more than one-third of adults do not respond to MPH.
“These findings suggest that those who respond to MPH and those who do not may represent different biological subgroups within the adult population. This work can help us understand why treatments are not universally effective, which will ultimately help advance the development of more targeted clinical interventions,” says Dr. Valeria Parlatini.
The study focused only on male individuals, with ADHD more commonly diagnosed in men and following preliminary evidence of sex differences in brain anatomy and biological response to stimulants.
“This is one of the first studies to investigate differences in neuroanatomy related to response to treatment focused exclusively on adults with ADHD. Anatomical studies to date comparing responders and non-responders have included only children or a mixed sample of children and adults, have not included neurotypical controls for comparison, and have relied primarily on volumetric measurements,” says Professor Declan Murphy.
The researchers stress that the findings need to be replicated and extended in further independent studies to increase understanding of why some individuals are resistant to treatment.
This in turn would help advance the development of clinical interventions by identifying treatment-resistant individuals in the context of clinical trials of new treatments.
ADHD drugs linked to reduction in psychiatric hospitalizations
For adolescents and adults with attention-deficit/hyperactivity disorder (ADHD), use of ADHD medications is associated with fewer psychiatric and non-psychiatric hospitalizations.
Heidi Taipale, Ph.D., of the Karolinska Institutet in Stockholm, and colleagues examined the association between the use of specific medications and outcomes of hospitalization and work disability in a nationwide registry-based cohort study that involved adolescents and adults with ADHD from 2006 to 2021. The study cohort included 221,714 people.
The most commonly used ADHD medication was methylphenidate, followed by lisdexamfetamine (68.5 and 35.2%). The researchers found that amphetamine, lisdexamfetamine, polypharmacy, dexamphetamine, and methylphenidate were associated with a reduced risk of psychiatric hospitalizations (adjusted hazard ratios, 0.74, 0.80, 0.85, 0.88 and 0.93, respectively).
No associations were observed for modafinil, atomoxetine, clonidine or guanfacine. The use of dexamphetamine, lisdexamfetamine, and methylphenidate was associated with a reduced risk of suicidal behavior (adjusted hazard ratio, 0.69, 0.76, and 0.92, respectively).
Amphetamine, lisdexamfetamine, polypharmacy, dexamphetamine, methylphenidate, and atomoxetine were associated with a reduced risk of nonpsychiatric hospitalization. Regarding work disability, the results were significant only for the use of atomoxetine (adjusted hazard ratio, 0.89), especially for subjects aged 16 to 29 years (adjusted hazard ratio, 0.82) .
“Considering the high prevalence of psychiatric comorbidity in people with ADHD, these findings suggest that the use of medications may reduce morbidity in adolescents and adults with this diagnosis,” the authors write.
Should ADHD Medication Be Stopped During Pregnancy?
“ADHD is becoming more commonly diagnosed in women; as a result, more and more women are taking ADHD medications such as dexamphetamine during pregnancy,” Russell said. “Our study investigated whether there were reasons to stop taking this drug during pregnancy.”
The research included women from Western Australia who had taken dexamphetamine during pregnancy and had given birth between 2003 and 2018.
“Women who stopped taking the drugs during pregnancy had a higher risk of threatened pregnancy loss than those who continued taking them,” Russell said. “However, the findings indicated that continuing to take dexamphetamine does not expose women or their children to increased health risks.”
The study found that there also appeared to be benefits associated with stopping medication use before conception, including a decreased risk of preeclampsia, hypertension, postpartum hemorrhage, admission to a special care unit and fetal distress.
Pregnancy can be a really stressful time for women with ADHD, so it's good to know that stopping your medications during pregnancy may not always be necessary,” she said.
The research is part of larger work being conducted with the guidance of women in the ADHD community, in the hope of providing much-needed information about treatment during pregnancy.
Prenatal exposure to ADHD medications linked to neonatal morbidity
Exposure to attention-deficit/hyperactivity disorder (ADHD) medications during pregnancy is associated with an increased risk of neonatal morbidity, according to a study published online in Pediatrics.
Ulrika Nörby, Ph.D., of Lund University in Sweden, and colleagues examined perinatal outcomes for singleton infants born between 2006 and 2014 in Sweden after maternal use of ADHD medications during pregnancy . Infants exposed to ADHD medications during pregnancy were compared with infants whose mothers had never used these drugs and with infants whose mothers had used ADHD medications before or after pregnancy.
The researchers found that 0.2 percent of the 964,734 newborns were exposed to ADHD medications during pregnancy, and 1 percent had mothers treated before or after pregnancy. Compared with nonuse and use before or after pregnancy, exposure during pregnancy was correlated with an increased risk of admission to a neonatal intensive care unit (adjusted odds ratios, 1.5 and 1, respectively). 2).
Compared to unexposed infants, infants exposed during pregnancy more often had central nervous system-related disorders and were more often moderately premature (adjusted odds ratios, 1.9 and 1.3, respectively). The risk of congenital malformations or perinatal death was not increased.
“Treatment with ADHD medications during pregnancy has been associated with a higher risk of neonatal morbidity, particularly central nervous system-related disorders such as seizures. Because of large differences in baseline characteristics between treated women and controls, it is unclear to what extent this can be explained by ADHD medications per se,” the authors write.
ADHD medications associated with reduced risk of car crashes
In a study of more than 2.3 million patients in the United States with attention-deficit/hyperactivity disorder (ADHD), motor vehicle accident (MVC) rates were lower when they received the medications, according to an article published by JAMA Psychiatry .
Approximately 1.25 million people worldwide die from CVDs each year. ADHD is a prevalent neurodevelopmental disorder with symptoms that include poor sustained attention, impaired impulse control, and hyperactivity.
ADHD affects 5% to 7% of children and adolescents and persists into adulthood for many people. Previous studies have suggested that people with this diagnosis are more likely to experience MVC.
Pharmacotherapy is a first-line treatment for the condition, and rates of prescribing ADHD medications have increased over the past decade in the United States and other countries.
Zheng Chang, Ph.D., M.Sc., of Karolinska Institutet, Stockholm, Sweden, and coauthors identified more than 2.3 million U.S. patients with ADHD between 2005 and 2014 from commercial health insurance claims and identified emergency department visits for MVC. The analyzes compared the risk of MVC during the months in which patients received the drugs with the risk of MVC during the months in which they did not receive them.
Among more than 2.3 million patients with ADHD (average age 32.5 years), 83.9% (more than 1.9 million) received at least one prescription for ADHD medication during follow-up . There were 11,224 patients (0.5%) who had at least one emergency room visit for a MVC.
Patients with ADHD had a higher risk of MVC than a control group of people who did not have ADHD or use medications. According to the findings, the use of medications in patients with this diagnosis was associated with a reduced risk of MVC in both male and female patients.
“These findings call attention to a prevalent and preventable cause of mortality and morbidity among patients with ADHD. If replicated, our findings should be considered alongside other potential benefits and harms associated with drug use,” the article concludes.
Limitations of the study include that it cannot prove causality because it is an observational study. Medication use was also measured through prescriptions filled monthly. Additionally, the study used emergency room visits due to MVC as the primary outcome, so some MVCs that did not require medical services (e.g., less serious incidents or some fatalities) were not included in the study.
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