There remains no approved treatments for fragile X syndrome (FXS), the leading inherited cause of intellectual disabilities and autism spectrum disorder (ASD) worldwide.

However, preclinical models show kappa opioid receptor antagonists have therapeutic potential to help treat the disorder.

2021 American Professional Society of ADHD and Related Disorders (APSARD)

 Annual Virtual Meeting, a team of researchers presented data showing kappa opioid receptor antagonists could eventually be a much needed viable treatment for fragile X syndrome.

, Deirdre McCarthy, Department of Biomedical Sciences, Florida State University College of Medicine, explained the promising results and what the plans are to further study this treatment in larger human trials.

McCarthy discussed why it is so difficult to find a suitable treatment for fragile X syndrome and how this treatment is surprisingly promising for this disease.

McCarthy said kappa opioid receptor antagonists have been used in preclinical models as a treatment for addiction disorders and pain, which led the researchers to the belief that it could be a potential therapy for fragile X syndrome.

These drugs can modulate therapeutic transmitters in the brain.

McCarthy said there are also many different drugs that are showing promise in preclinical models.

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There is currently no approved treatment for fragile X syndrome.

Deirdre McCarthy: The Long Pursuit of a Fragile X Syndrome Treatment

Although evidence demonstrates that stimulants offer protective effects for adults with 

, there is nonetheless an issue with non-adherence among the patient population. It is estimated that up to 87% of these patients fail to adhere to stimulant treatment.

Furthermore, as opposed to pediatricians, primary care providers may be less equipped and familiar with the diagnosis and therapeutic strategies of ADHD. Therefore, it becomes necessary to provide novel interventional tools—especially in the primary care setting—in order to increase adherence and optimize treatment for these patients.

A team led by Ronna Fried, EdD, Director of Paradigm Development, Massachusetts General Hospital, demonstrated that a text messaging-based (SMS) intervention system significantly improved patient adherence to stimulant treatments.

The team enrolled a total of 112 adults aged 18-55 years, all of whom came from primary care and psychiatric practices.

“All participants received a customized ADHD-centric text message program that included reminders to adhere to the individualized medication regimen and to contact their clinician for a prescription refill followed by reminders to pick up medication from the pharmacy,” Fried and colleagues wrote.

Patients also received educational reminders regarding ADHD and its treatment. All patients received text messages for at least 37 days.

The investigators then used the Partners HealthCare electronic medical record (EMR) to match participants with patients who had been prescribed stimulant medications over a 1-year period (n = 336). Matching was done according to age, race, and sex.

They defined a patient’s index prescription accordingly. For those identified from the EMR system, index was considered the first stimulant prescription on record during the study time frame.

For patients receiving the SMS intervention, index was the date that text messaging initiated for them.

Fried and team then used documented prescription records to determine whether patients had timely refills.

As such, 81% in the SMS intervention group refilled their prescriptions in a timely manner—compared with 36% of patients receiving usual care and treatment (OR=7.54, 95% CI: 4.46, 12.77; 

The team also found that there was no significant interaction between the prescribing clinic and intervention group. This suggests, then, that the prescribing source may have no effect on improvement in adherence rate.

“[These] findings provide support for this accessible and inexpensive technology to improve the poor adherence rate to stimulant treatment in adults with ADHD,” the investigators concluded.

The study, “A Novel Digital Health Intervention to Improve Adherence to Stimulants in Adults With ADHD in the Primary Care Setting,” was presented at APSARD 2021.

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Current estimates indicate that non-adherence to stimulants is as high as 87%. 

Novel SMS Strategy May Help Increase Stimulant Adherence in Adults with ADHD

Timing and regularity of sleep could be a crucial factor in symptoms and social functioning associated with 

, according to new research presented at 

The American Professional Society of ADHD and Related Disorders (APSARD) 2021 Annual Conference

The new data from research conducted by investigators at the Duke University Medical Center—and presented by Jessica Lunsford-Avery, PhD, a child development and behavioral health specialist—supports the long-held notion of sleep as a vital element in adolescent behavioral health relevant to ADHD.

In fact, it is the “complexity of sleep,” Lunsford-Avery and colleagues wrote, which has made it previously difficult to determine the aspects of sleep which influence adolescent ADHD outcomes, beyond just duration.

“Sleep supports adolescent behavioral health and functioning, particularly among teens with ADHD,” they wrote. “This study examined associations between two sleep indices (regularity, timing) and (1) ADHD symptoms and (2) academic/social functioning over and above the impact of shortened/fragmented sleep.”

In the study, funded by the Duke Institute for Brain Sciences and National Institute of Mental Health, investigators recruited 90 adolescents from the research institution’s community for their assessment. Mean patient age was 14.08 years old, with 46% reported as female.

Patients underwent 7 days and nights of actigraphy, and reported on ADHD symptom severity, as well as academic and social functioning, with additional comment from their parent/guardian.

The team controlled for sex, age, and race factors using stepwise linear regressions, and examined for associations between sleep timing and regulatory with ADHD and functional outcomes—after accounting for shortened/fragmented sleep.

Lunsford-Avery and colleagues observed that delayed sleep timing as linked to greater self-reported ADHD symptoms (

= .02) after accounting for shortened or fragmented sleep.

What’s more, irregular sleep was linked to greater patient- and parent-reported symptoms of ADHD (

 <.001, respectively), as well as lower social function (

 = .02, respectively). Lower academic functioning was also associated with irregular sleep, as per both patient and parent reports.

Investigators concluded that both sleep regularity and timing may be crucial to adolescent patients with ADHD achieving ideal attention and daytime functioning. In fact, both outcomes could inform potential intervention and interventional studies.

“Future work should focus on developing and evaluating convenient, low-cost, and effective methods for addressing delayed and/or irregular sleep patterns in ADHD populations,” they wrote.

The study, “Sleep Regularity and Timing Associated With ADHD Severity and Academic/Social Performance in Adolescents,” was presented at APSARD 2021.

New research expands on the understood link between sleep and ADHD-related behavior, and gives clinicians new therapeutic targets.

Sleep Regularity, Timing Could Influence ADHD Symptoms in Teens

Impulsivity, as measured in patients with disorders including 

, was associated with greater risk of distress in afflicted patients during the 

 this weekend suggested traits of impulsivity could have a notable and negative interaction with stress related to COVID-19. Investigators from the MIND Institute at University of California Davis School of Medicine believe the observed correlation could inform individualized psychiatric care for at-risk patients during future crises such as the pandemic.

The data, presented by Prerona Mukherjee, PhD, examined the associations between psychological distress or concern and precautions taken or exposure-risk, as they pertain to impulsivity and goal-orientation metrics. They hypothesized that goal-orientation could predict precautions taken, while impulsivity could predict concern and distress.

“The COVID-19 crisis introduced several stressors for most people,” investigators wrote. “Traits such as impulsivity, which is associated with multiple disorders including ADHD, could interact with COVID-19 related stress by interfering with decisions and perceptions of risk or concerns.”

Mukherjee and colleagues remotely assessed 31 individuals via a COVID-19 related questionnaire which gauged the at-risk group on a litany of statuses:

Impulsivity and future orientation, via Zimbardo Time Perspective Inventory (ZTPI)

The team conducted two-tailed Bivariate Pearson Correlations via SPSS.

Investigators found impulsivity correlated with greater distress in observed individuals during the COVID-19 pandemic (

 = .037; r = .377). Goal-oriented behavior, conversely, was associated with lower distress (

 = .031; r = -0.388) as well as lower concern (

They observed no correlations between impulsivity or goal-orientation with actual risk faced, nor precautions taken by individuals.

“These findings illustrate that impulsivity and goal orientation predicted the psychological impact experienced during the COVID-19 crisis, regardless of the risk an individual faced,” investigators wrote.

Additionally, the predictive value of goal orientation in lessened psychological impact—but not of precautions taken—could guide ideas for individualized psychological intervention in crises.

More specifically, this could indicate potential to tailor care for patients with ADHD during the ongoing pandemic.

“Furthermore, this data from a longitudinal study may lead to future work investigating long-term impact and other factors,” Mukherjee and colleagues concluded.

The study, “COVID-19 and Its Psychological Impact: The Role of Impulsivity,” was presented at APSARD 2021.

Though the correlation is concerning for at-risk groups, experts believe it could inform individualized psychiatric care during crises.

ADHD Impulsivity Linked to Greater COVID-19 Distress

Findings from a new study indicate that telehealth services are a valid means of offering neuropsychological assessment in children with 

The study, presented this weekend at the 

2021 American Professional Society of ADHD and Related Disorders (APSARD

)Annual Virtual Meeting, was conducted to evaluate the disruptions in healthcare stemming from the 

coronavirus disease 2019 (COVID-19) pandemic

“The rapid transition to telehealth services due to the COVID-19 pandemic prompted debate regarding the comparability of neuropsychological assessments administered via teleconference versus those administered in-person, given that norms are based on in-person administration of these measures,” the investigators wrote.

The team, led by Kristie Sweeney, MS, Kennedy Krieger Institute, thus determined whether telehealth systematically disadvantaged children with ADHD.

They evaluated a total of 365 onsite/in-person testing visits and 142 virtual (Zoom) visits through the Kennedy Krieger Institute clinic.

Further, the in-person sample consisted of all testing visits 4.5 months prior to March 2020, while the virtual visits occurred within 4.5 month following reopening of the clinic.

Patients in the virtual cohort were matched to those in the in-person cohort according to age (mean, 10.45 years), sex (68% male), insurance type (43% medical assistance, 57% commercial insurance).

In both modalities, the WISC-V Matrix Reasoning, Similarities, Vocabulary, Digit Span; KTEA-3 Math Concepts, Letter & Word Recognition; DKEFS Verbal Fluency; and NEPSY-II Word Generation assessments were performed.

The investigators then used 2 sample t-tests to compare the scores obtained from the aforementioned assessments through onsite and virtual visits. 

Sweeney and colleagues reported no significant differences between administration modalities for the WISC-V, DKEFS, and NEPSY subtests, in addition to the KTEA-3 Letter/Word subtest (

Interestingly, the KTEA-3 Math Concepts scores were noted to be significantly higher for telehealth administration (SS = 90.28) than for in-person administration (SS = 85.44; 

“With the exception of Math Concepts, which requires more investigation, results suggest that modality of neuropsychological evaluation (onsite/in-person vs. telehealth) does not affect performance for children with ADHD, and that telehealth services may be a valid way to assess this population,” the team wrote.

They indicated that improved Math Concepts scores via telehealth may be due to clinicians checking in on patients more often to ensure connectivity and task engagement. As such, this would provide increased redirection and support to aid variability in attention.

Sweeney and her team acknowledged a need to explore further these factors that may have contributed to an improved performance through telehealth service.

Additionally, they believed future research should seek to compare an ADHD cohort with the non-ADHD population.

The study, “Performance on Neuropsychological Assessments Administered in Person Compared to Telehealth for Children With ADHD,” was presented at APSARD 2021.

The APSARD study finds that most neuropsychological assessment scores did not differ significantly between both in-person and virtual visit modalities. 

ADHD Assessments Conducted Via Telehealth May Not Disadvantage Children

attention deficit/hyperactivity disorder (ADHD)

 long seek new treatments with delayed or extended release action.

The short-term release, while effective, force the patient to carry the treatments with them while they are at work, school, or anywhere else outside of the home.

American Professional Society of ADHD and Related Disorders (APSARD) 2021 Annual Conference

, investigators presented new data promoting methylphenidate as a treatment for ADHD with both an extended and delayed release action.

The researchers found the treatment resulted in improvements in ADHD symptoms, as well as improvements in early morning functional impairments for children between 6-12 years old.

, Andrew J. Cutler, MD, Clinical Professor of Psychiatry at SUNY Upstate Medical University, discussed the value of extended release medication and how it can aid patients in improving their quality of life.

In addition, Cutler explained exactly how delayed reaction medications work inside the body and why they are difficult to develop. This treatment could potentially be taken in the evening, enabling the delayed reaction to take effect in the morning.

By doing this, clinicians can prevent peak bursts of effectiveness, in favor of slowly helping the bookend times of morning and late afternoon for patients.

Methylphenidate has shown promising boosting morning function in pediatric patients with ADHD.

Andrew J. Cutler, MD: The Value of Delayed Release ADHD Treatments

Omega-3 fatty acids plus inositol may serve as a significantly beneficial therapy for children and adolescents with 

 this weekend, a team of investigators from the Massachusetts General Hospital and Harvard Medical School reported significant improvements to bipolar disorder symptoms with monotherapy and combination use of fatty acids and/or inositol over 12 weeks.

Presented by Janet Wozniak, MD, associate professor of Psychiatry at Harvard Medical School, the findings could indicate a viable alternative therapy regimen for younger patients with the disorder.

Wozniak and colleagues sought to assess the efficacy, safety, and tolerability of omega-3 fatty acids and inositol as both monotherapies and in combination for treating pediatric bipolar spectrum disorder.

They referenced recent research suggesting inositol, a central nervous system-based carbocyclic sugar, plays a role in mood disorder pathophysiology. “Inositol is decreased in the cerebrospinal fluid of patients with depression and is involved in the second messenger system for numerous neurotransmitter receptors,” investigators wrote.

Their phase 3, 12-week, double-blind, controlled assessment of the therapies included patients aged 5-12 years old with diagnosed bipolar disorder. Patients were randomized to 3 different treatment arms: inositol plus placebo, omega-3 fatty acids plus placebo, or combination therapy.

A series of scales and tests were used to assess mania and depression symptoms associated with each treatment arm:

Children’s Depression Rating Scale (CDRS)

Clinical Globe Impression (CGI) Severity (CGI-S) Scale

At 12 weeks, investigators observed significant reductions in YMRS and HDRS mean scores from baseline in all 3 treatment arms. Mean CDRS scores were significantly reduced among young patients receiving omega-3 fatty acids plus placebo, but even more so among those receiving combination therapy.

The fatty-acid plus inositol treatment arm reported the greatest rates of anti-manic and antidepressant response at 30% and 50% reductions, respectively, in YMRS, HDRS, and CDRS scores. CGI-I mania and depression scores for the treatment are were ≤2 at endpoint, indicating significant improvement.

Overall, Wozniak and colleagues concluded the findings indicate promise for a trio of pediatric bipolar therapy options.

“Omega-3 fatty acids and inositol both alone and in combination may be effective safe alternative and natural treatment for pediatric BP spectrum disorder,” they wrote. “Furthermore, the combined treatment may be more effective than either treatment alone.”

The study, “A Randomized, Double-Blind, Controlled Clinical Trial of Omega-3 Fatty Acids and Inositol as Monotherapies and in Combination for the Treatment of Pediatric Bipolar Spectrum Disorder,” was presented at APSARD 2021.

Both monotherapy and combination of the unique regimen was shown to improve manic and depressive status at 12 weeks.

Omega-3 Fatty Acids, Inositol Could Benefit Pediatric Bipolar Disorder

The Child Behavior Checklist (CBCL) may be useful in characterizing comorbidity in children referred to a clinician for 

2021 American Professional Society of ADHD and Related Disorders (APSARD)Virtual Meeting

 demonstrated that a majority of clinically referred children with suspected ADHD also presented with comorbid psychopathology.

Further, these comorbidities were measured according to the CBCL’s individual and composite clinical scales.

A team led by Joseph Biederman, MD, Chief, Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Massachusetts General Hospital, evaluated whether or not the CBCL would be useful in characterizing such comorbid psychopathy.

They acknowledged that assessment of ADHD-related comorbidity in clinical practice has long been lacking in research.

“Previous research documented excellent convergence between the CBCL and DSM-based disorders,” Biederman and colleagues wrote. 

“Because it is a simple to use, parent completed questionnaire assessing various dimensions of psychopathology, it facilitates the characterization of comorbid psychopathology in children with ADHD in clinical practice,” they continued.

The team thus assessed a sample consisting of 332 newly referred children 4-18 years of age. All patients were identified with suspected ADHD, defined as having CBCL Attention Problems T-scores ≥60, for example.

Using the CBCL, the investigators evaluated additional psychopathology through examination of abnormal T-scores on individual, composite, and unique profile scales. These scores were considered proxies for additional comorbid disorders.

Thus, they found that 76% of these children had ≥3 additional abnormal CBCL scales, which further suggests a likelihood that they were affected with other comorbid psychiatric disorders.

“Moreover, 44% of youth with suspected ADHD had at least one other CBCL clinical scale with a T-score more severe (≥0.5 standard deviation higher) than their CBCL Attention Problems T-score,” the team wrote.

According to their results, 13% of patients had the Anxious/Depressed scale as their most severe scale, while 11% had the Aggressive Behavior scale as their most severe scale, and 8% had the Withdrawn/Depressed scale has their most severe scale.

The investigators noted few differences between male and female as well as children and adolescents.

As such, the CBCL provided relevant information about the types and severity of suspected psychopathological conditions that may affect youth. This information can then be useful in guiding clinicians in their assessment of differing clinical and therapeutic needs of their patients. 

“These findings have implications for the clinical care of youth with ADHD and for improved consideration of the complexity of clinical presentations of children with ADHD in any clinical setting,” Biederman and colleagues wrote.

The study, “Can the Child Behavior Checklist Characterize Comorbidity in Clinically Referred Youth With ADHD?” was presented at APSARD 2021.

The Child Behavior Checklist may provide invaluable information to clinicians regarding the type and severity of comorbid psychopathologies. 

Comorbidities Related to Pediatric ADHD May Be Characterized Using CBCL

Methylphenidate could be a crucial treatment for adolescent patients with 

 (ADHD) in a delayed-release and extended-release formulation.

 a team of investigators presented new data showing the treatment resulted in improvements in ADHD symptoms and early morning functional impairment for children between 6-12 years old with the disorder.

The researchers tested the treatment in a 20 or 40 mg per dose phase 3 trial involving 125 adolescent patients with a mean age of 9.4 years.

Over the course of the 6 week study, mean ADHD-Rating Scale-IV scores decreased from 42.5 at baseline to 11.00 at week 6, while Before School Functioning Questionnaire (BSFQ) scores improved after 1 week of treatment.

The researchers also found that the proportion of patients who achieved symptomatic and early morning functional impairment response and remission thresholds increased after each week of treatment.

When doses were titrated weekly, with the aim of control throughout the day, most patients achieved response and remission thresholds, with early morning and late afternoon/evening functional impairment found at the end of the six-week, treatment optimization period.

, Andrew J. Cutler, MD, Clinical Professor of Psychiatry at SUNY Upstate Medical University, explained the positive results presented at APSARD.

The treatment improves morning function for adolescent ADHD patients.

Andrew J. Cutler, MD: Delayed and Extended Release Methylphenidate Shows Promise

The US Food and Drug Administration (FDA) has approved daratumumab and hyaluronidase-fihj (DARZALEX FASPRO) in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) for the treatment of adult patients newly diagnosed with 

The decision makes the combination therapy the first indicated for patients with the rare, possibly fatal blood disorder.

AL amyloidosis is associated with abnormal protein production which leads to vital organ deterioration. Patients afflicted with the rare disease may suffer severe damage to their heart, kidneys, and/or liver. Up to 30% of the 4500 patients diagnosed in the US annually can die within the first year.

The FDA approval was based on the phase 3 findings from the ANDROMEDA study, in which the combination was assessed with VCd, versus lone VCd therapy, in patients with AL amyloidosis. Investigators reported at the American Society of Hematology (ASH) 2020 Annual Meeting that patients treated with the daratumumab and hyaluronidase combination experienced a three-fold improved hematologic complete response rate versus patients given lone VCd (42% vs 13%; 

® utilizing our ENHANZE® technology has become the first and only FDA-approved treatment for newly diagnosed patients with AL amyloidosis," said Helen Torley, MD, president and chief executive officer of Halozyme Therapeutics, 

. "AL amyloidosis represents an area of high unmet medical need."

 on the ongoing phase 3 trial back in 2018, alluding to the hope that DARZALEX FASRPO could eventually top VCd as the standard of therapy.

“It’s a very exciting prospect for the newly diagnosed amyloid patients of the future to potentially have a combination of 4 drugs that are safe and that are almost 100% effective,” Comenzo said at the time. “That’s what we expect; we expect many, many patients to be effectively treated and to recover.”

, Janssen Pharmaceutical was granted FDA approval for daratumumab and hyaluronidase as a multiple-regimen subcutaneous formulation for the treatment of patients with multiple myeloma—4 regimens approved for 5 multiple myeloma indications.

The indication is the first of its kind for the rare, sometimes quickly fatal disease.

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