July 25, 2024
Dasotraline is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) that had been under development by Sunovion for treating ADHD and binge eating disorder.
An Indian research team conducted a systematic search of the peer-reviewed medical literature to perform meta-analyses of the quantitative outcomes of clinical trials.
Meta-analysis of five double-blinded randomized clinical trials (RCTs) with a combined total of 1,498 participants reported a small-to-medium effect size reduction in ADHD symptoms in patients given dasotraline as opposed to those given placebo.
There were, however, strong indications of publication bias. Using the trim-and-fill procedure to correct for that bias yielded a small effect size reduction in ADHD symptoms in patients given dasotraline compared with those given placebo.
Insomnia were more than four times more frequent among patients given dasotraline than among those given placebo. There was no evidence of the frequency of insomnia being dose-dependent.
Similarly, patients given dasotraline were more than four times more likely to report decreased appetite than those receiving placebo. In this case, however, the effect was clearly dose-dependent, rising from 3x for 2mg to 4x for 4mg to 5x for 6mg and almost 8x for 8mg.
The authors concluded, “dasotraline can reduce the core symptoms of ADHD, that is, hyperactivity/impulsivity and inattentiveness, leading to an overall improvement of ADHD compared to placebo. Dasotraline can also improve clinician-determined patients’ global functioning compared to the placebo. The most common adverse drug reactions related to dasotraline were insomnia and decreased appetite. However, to fill the knowledge gap, multicentric randomized active-controlled clinical trials are warranted in this domain for a successful translation into clinical practice.”
Weighing these less than impressive initial results against the cost of further RCTs, Sunovion withdrew its application for approval by the Food and Drug Administration, stating, “while Sunovion considers dasotraline to be a promising, novel treatment for binge eating disorder and ADHD, we believe that further clinical studies would be needed to support a regulatory approval for dasotraline in these indications.”
Rituparna Maiti, Archana Mishra, Monalisa Jena, Shampa Maji, Milan Padhan, Biswa R. Mishra, “Efficacy and safety of dasotraline in attention‐deficit hyperactivity disorder: A systematic review and meta‐analysis,” Indian Journal of Psychiatry (2024), https://doi.org/10.4103/indianjpsychiatry.indianjpsychiatry_3_24.
Brian Park, “Dasotraline Development for ADHD, Binge Eating Disorder Halted, NDAs Withdrawn,” Medica Professionals Reference, May 14, 2020, https://www.empr.com/home/news/drugs-in-the-pipeline/sunovion-withdraws-nda-dasotraline-development-binge-eating-adhd/.
Child abuse includes any of the following inflicted on a minor under 18 years old: physical or emotional harm, sexual abuse, or neglect.
It is known to be associated with environmental factors such as poverty, parents or neighbors with a history of violence, and gender inequality.
Chronic mental disorders in minors are also associated with child abuse. To what extent, if any, might that be true of ADHD?
Taiwan has a single-payer national health insurance system that covers more than 99.6% of all residents, enabling nationwide population studies.
A local research team used data from almost two million Taiwanese in their country’s National Health Insurance Research Database (NHIRD) spanning 15 years (2000-2015) to carry out a matched-cohort study.
All diagnoses of ADHD were made by board-certified specialists such as psychiatrists, pediatricians, neurologists, or physiatrists with a specialty in child and adolescent development.
3,540 children and adolescents between 6 and 18 years old with a diagnosis of ADHD were matched on a one-to-three basis with 10,620 peers from the NHIRD without an ADHD diagnosis.
The team adjusted for age, gender, location of residence (Northern, Central, Southern, and Eastern Taiwan), urbanization level of residence, level of hospitals as medical centers, and monthly insured premium. They further adjusted for comorbid conditions: intellectual disability, autistic disorder/pervasive developmental disorder, conduct disorder (CD)/oppositional defiant disorder (ODD), other developmental disorders, childhood emotional disorder, Tourette syndrome/tics disorders, and involuntary urination and defecation.
Overall, children and adolescents with an ADHD diagnosis were 1.8 times as likely to be abused as those without an ADHD diagnosis.
Unmedicated children and adolescents with an ADHD diagnosis were three times more likely to be abused. ADHD medication cut that risk in half.
That held true whether the medication used was methylphenidate or atomoxetine. Methylphenidate appeared to be slightly more effective than atomoxetine, and the combination of methylphenidate and atomoxetine slightly more effective yet, but these differences were not statistically significant.
The team concluded, “The results support that pharmacotherapy may attenuate the risk of child abuse in ADHD patients.”
A Chinese research team performed two types of meta-analyses to compare the risk of suicide for ADHD patients taking ADHD medication as opposed to those not taking medication.
The first type of meta-analysis combined six large population studies with a total of over 4.7 million participants. These were located on three continents - Europe, Asia, and North America - and more specifically Sweden, England, Taiwan, and the United States.
The risk of suicide among those taking medication was found to be about a quarter less than for unmediated individuals, though the results were barely significant at the 95 percent confidence level (p = 0.49, just a sliver below the p = 0.5 cutoff point). There were no significant differences between males and females, except that looking only at males or females reduced sample size and made results non-significant.
Differentiating between patients receiving stimulant and non-stimulant medications produced divergent outcomes. A meta-analysis of four population studies covering almost 900,000 individuals found stimulant medications to be associated with a 28 percent reduced risk of suicide. On the other hand, a meta-analysis of three studies with over 62,000 individuals found no significant difference in suicide risk for non-stimulant medications. The benefit, therefore, seems limited to stimulant medication.
The second type of meta-analysis combined three within-individual studies with over 3.9 million persons in the United States, China, and Sweden. The risk of suicide among those taking medication was found to be almost a third less than for unmediated individuals, though the results were again barely significant at the 95 percent confidence level (p =0.49, just a sliver below the p = 0.5 cutoff point). Once again, there were no significant differences between males and females, except that looking only at males or females reduced the sample size and made results non-significant.
Differentiating between patients receiving stimulant and non-stimulant medications once again produced divergent outcomes. Meta-analysis of the same three studies found a 25 percent reduced risk of suicide among those taking stimulant medications. But as in the population studies, a meta-analysis of two studies with over 3.9 million persons found no reduction in risk among those taking non-stimulant medications.
A further meta-analysis of two studies with 3.9 million persons found no reduction in suicide risk among persons taking ADHD medications for 90 days or less, "revealing the importance of duration and adherence to medication in all individuals prescribed stimulants for ADHD."
The authors concluded, "exposure to non-stimulants is not associated with a higher risk of suicide attempts. However, a lower risk of suicide attempts was observed for stimulant drugs. However, the results must be interpreted with caution due to the evidence of heterogeneity ..."
A team from Harvard Medical School and Massachusetts General Hospital conducted a six-week open-label trial of liquid-formulation extended-release methylphenidate (MPH-ER) to treat ADHD in adults with high-functioning autism spectrum disorder (HF-ASD). ASD is a lifelong disorder with deficits in social communication and interaction and restricted, repetitive behaviors. Roughly half of those diagnosed with ASD also are diagnosed with ADHD.
This was the first stimulant trial in adults with both ASD and ADHD. There were twelve males and three female participants, all with moderate to severe ADHD, and in their twenties, with IQ scores of at least 85.
The use of a liquid formulation enabled doses to be raised very gradually, starting with a daily dose of 5 mg(1mL) and titrating up to 60 mg over the first three weeks, then maintaining that level through the sixth week. Participants were reevaluated for ADHD symptoms every week during the six-week trial. The severity of ASD was assessed at the start, midpoint, and conclusion of the trial, as were other psychiatric symptoms.
Before the trial, researchers agreed on a combination of targets on two clinician-rated scoring systems that would have to be reached for treatment to be considered successful. One is a score of 2 or less on the CGI-S, a measure of illness severity, with scores ranging from 1 (normal, not at all ill) to 7 (most extremely ill). The other is a reduction of at least 30 percent in the AIS RS score, which combines each of 18 symptoms of ADHD on a severity grid (0=not present; 3=severe; overall minimum score: 0; overall maximum score: 54).
After the trial, twelve of the fifteen patients (80 percent) met the preset conditions for success. Fully fourteen (93 percent) saw a ≥ 30 percent reduction in their AISRS score, while twelve scored ≤ 2 on illness severity.
However, when using the patient-rated ASRS scoring system, only five (33 percent) saw a ≥ 30 percent reduction in ADHD severity.
Thirteen participants (87percent) reported at least one adverse event, and nine (60 percent) reported two or more. One reported a serious adverse event (attempted suicide) in a patient with multiple prior attempts. Because the attempt was not deemed due to medication, they continued and completed the trial. Seven participants experienced titration-limiting adverse events (headaches, palpitations, jaw pain, and insomnia). Headache was most frequent (53%), followed by insomnia and anxiety(33% each), and decreased appetite (27%).
During the trial, weight significantly decreased, while pulse significantly increased. There were no significant differences in other vital and cardiovascular measurements.
The authors concluded, "this OLT of short-term MPH-ER therapy documents that acute treatment with MPH-ER in young adults with ASD was associated with significant improvement in ADHD symptoms, mirroring the typically-expected magnitude of response observed in adults with only ADHD. Treatment with MPH-ER was well-tolerated, though associated with a higher than expected frequency of adverse events."
They also cautioned, "The results of this study need to be considered in light of some methodological limitations. This was an open-label study; therefore, assessments were not blind to treatment. We did not employ a placebo control group and, therefore, cannot separate the effects of treatment from time or placebo effects. ... firmer conclusions regarding the safety and efficacy of MPH-ER for the treatment of ADHD in HF-ASD populations await results from larger, randomized, placebo-controlled clinical trials."
A recent U.S. study challenges assumptions about the link between prescription stimulant use for ADHD and later substance abuse. Adolescents who used prescription stimulants under a physician’s supervision did not exhibit increased rates of non-medical stimulant use or cocaine use as they transitioned into young adulthood. However, other factors, like binge drinking and cannabis use, showed significant associations with later substance misuse, suggesting that the landscape of risk is more complex than previously understood.
Prescription stimulants are considered one of the most effective treatments for ADHD. While these medications can significantly improve focus and behavior, concerns have persisted that using stimulants during adolescence might predispose individuals to substance use disorder (SUD). Some theories suggest that early exposure to stimulants could increase the likelihood of cocaine use, as both substances affect the brain's dopamine pathways similarly.
Yet, previous research often lacked large, longitudinal studies focusing on adolescents with ADHD who had never been treated with stimulants. To fill this gap, a research team followed a nationally representative cohort of 11,905 high school seniors (12th graders, mostly aged 18) for six years, tracking their substance use behaviors.
At the start of the study, participants completed surveys regarding their ADHD treatment history—whether they had used stimulant therapy, non-stimulant therapy, or no medication at all. This formed three groups:
Participants then completed follow-up surveys every two years, reporting on their use of substances like prescription stimulants and cocaine, as well as their engagement in behaviors like binge drinking and cannabis use.
The study found no significant differences in the rates of non-medical stimulant use or cocaine use among the three groups. Adolescents who had been prescribed stimulant medications were not more likely to misuse prescription stimulants or cocaine as young adults than those who had not received such medications.
However, other behaviors at age 18 showed strong associations with later substance use:
The study’s findings have important implications for both clinicians and families managing ADHD. Although ADHD is associated with an increased risk of SUD, the researchers observed no higher risk of nonmedical stimulant use among adolescents who had taken stimulant therapy compared to those who hadn’t. Additionally, there was no evidence that stimulant medications posed a greater risk than non-stimulant medications for subsequent misuse.
The findings also highlight the need for more robust screening for alcohol and other drug use among adolescents. As the study notes, current guidelines do not recommend routine screening for substance misuse in adolescents due to limited evidence. However, given the associations found between binge drinking, cannabis use, and later substance misuse, such preventive measures could play a key role in reducing risks during this vulnerable period of development.
Ultimately, the study sheds light on the multifaceted nature of substance use risks in adolescents and young adults, suggesting that while prescription stimulant use for ADHD under medical supervision may not directly contribute to substance abuse, the broader context of an adolescent’s behaviors and environment is crucial in shaping future outcomes.
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The report "Attention-Deficit/Hyperactivity Disorder Diagnosis, Treatment, and Telehealth Use in Adults" published in the CDC's Morbidity and Mortality Weekly Report provides a detailed examination of the prevalence and treatment of ADHD among U.S. adults based on data collected by the National Center for Health Statistics Rapid Surveys System during October–November 2023. This data is crucial as it offers updated estimates on the prevalence of ADHD in adults, a condition often regarded as primarily affecting children, and highlights the ongoing challenges in accessing ADHD-related treatments, including telehealth services and medication availability.
The methods used in this study involved the National Center for Health Statistics (NCHS) Rapid Surveys System (RSS), which gathers data to approximate the national representation of U.S. adults through two commercial survey panels: the AmeriSpeak Panel from NORC at the University of Chicago and Ipsos’s KnowledgePanel. The data were collected via online and telephone interviews from 7,046 adults. The responses were weighted to reflect the total U.S. adult population, ensuring that the results approximate national estimates. In identifying adults with current ADHD, respondents were asked if they had ever been diagnosed with ADHD and, if so, whether they currently had the condition. The study also collected data on treatment types (including stimulant and nonstimulant medications), telehealth use, and demographic variables such as age, education, race, and household income.
The results showed that approximately 6.0% of U.S. adults, or an estimated 15.5 million people, had a current ADHD diagnosis. Notably, more than half of the adults with ADHD reported receiving their diagnosis during adulthood (age ≥18 years), indicating that diagnosis can occur well beyond childhood. Analysis of demographics showed significant differences between adults with ADHD and those without; adults with ADHD were more likely to be younger, with 84.5% under the age of 50. Adults with ADHD were also less likely to have completed a bachelor's degree and more likely to have a household income below the federal poverty level compared to those without ADHD. Regarding treatment, the report found that approximately one-third of adults with ADHD were untreated, and around one-third received both medication and behavioral treatment. Among those receiving pharmacological treatment, 33.4% used stimulant medications, and 71.5% of these individuals reported difficulties in getting their prescriptions filled due to medication unavailability, reflecting recent stimulant shortages in the United States. Additionally, nearly half of adults with ADHD had used telehealth services for ADHD-related care, including obtaining prescriptions and receiving counseling or therapy.
The discussion emphasizes the public health implications of these findings. ADHD is often diagnosed late, with many individuals not receiving a diagnosis until adulthood, which underscores the need for improved awareness and early identification of ADHD symptoms across the life course. Moreover, the high prevalence of untreated ADHD and the barriers to accessing stimulant medications reveal significant gaps in the healthcare system's ability to support adults with ADHD. These gaps can contribute to poorer outcomes, such as increased risk of injury, substance use, and social impairment. The report also highlights the role of telehealth, which became more prominent during the COVID-19 pandemic. Telehealth appears to provide a viable solution for expanding access to ADHD diagnosis and treatment, though challenges remain regarding the quality of care and potential for misuse. The authors suggest that improved clinical care guidelines for adults with ADHD could help reduce delays in diagnosis and treatment access, thus improving long-term outcomes for affected individuals.
In conclusion, the study provides a comprehensive view of the prevalence, treatment, and telehealth use for ADHD among adults in the U.S. These data are crucial for guiding clinical care and shaping policies related to medication access and telehealth services. The findings underscore the importance of ensuring an adequate supply of stimulant medications and reducing barriers to ADHD care, ultimately enhancing the quality of life for adults with this condition. The good news is that many adults with ADHD are being diagnosed and treated. It is, however, concerning that many are not treated and that many of those treated with stimulants were impacted by the stimulant shortage.
For more details, see: https://www.cdc.gov/mmwr/volumes/73/wr/mm7340a1.htm
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60% to 90% of youth with ADHD continue to have symptoms as adults. In older adults, about 2.5% are believed to have ADHD, but it often goes unnoticed because research is limited and current diagnosis methods are based mostly on studies of young people.
Our commentary discusses key points about ADHD in older adults. Although 2 to 3 percent of older adults have ADHD when using proper diagnostic tools, only 0.23% are diagnosed in medical records. This shows that ADHD is greatly underdiagnosed in older adults. Even worse, less than 40% of those who are diagnosed receive any treatment, which highlights the need for doctors to be better educated about ADHD in this age group. Current ways of diagnosing ADHD need to be improved for people over 50. Also, there isn’t much research on ADHD medications for people over 60, with most studies excluding them, which raises concerns about how safe and effective these treatments are for older adults, especially since stimulant medications can affect the heart.
There are also biases among doctors that make it harder to diagnose and treat ADHD in older adults. Many doctors aren’t trained to recognize ADHD in this age group and still see it as a condition that only affects young people. Some think that if a person hasn’t been treated for ADHD by this stage in life, they don’t need treatment now. But this ignores the fact that untreated ADHD can cause lifelong struggles and reduce the person’s quality of life. Some doctors are also worried about the risks of ADHD medications for older patients, even though research shows that these medications are usually safe when properly monitored.
Diagnosing ADHD in older adults can be tricky because its symptoms can look similar to other conditions, like mild cognitive impairment or dementia. This makes it important for doctors to do a thorough assessment that looks at medical, psychiatric, and psychological factors. Since older adults often have other health issues, it’s crucial for doctors to tell the difference between ADHD symptoms and those caused by other conditions.
In the end, we need more awareness, training, and research on ADHD in older adults. Doctors need to push past biases and consider the benefits of treating ADHD in this age group, carefully weighing the risks and rewards. As the population of older adults grows, so does the need for studies and guidelines to provide better care for older people with ADHD. Filling these gaps will ensure that older adults with ADHD get the attention and treatment they need.
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