October 23, 2023

Safety and efficacy of long-term use of guanfacine for adults with ADHD

Guanfacine extended-release(GXR) is a non-stimulant α2A-adrenergic receptor agonist, approved worldwide for ADHD in children and adolescents.

A Japanese research team set out to explore the long-term administration of once-daily GXR in adults with ADHD over a year of treatment. Their primary objective was to evaluate the safety, and the secondary objective was to evaluate efficacy.

This was an open-label trial. Open-label trials are the opposite of double-blind trials. In a double-blind trial, neither the researchers nor the participants know what treatment they participants are receiving. In an open-label trial, on the other hand, both the researchers and participants know what treatment the participant is receiving, which can introduce significant bias. These studies are therefore at the lowest rung in the evidentiary base.

It is worth noting, however, that the risk of bias would be primarily for efficacy, and the primary aim of the trial was to evaluate safety.

The trial was funded by the manufacturer, but preregistered, a way of assuring that results would be released regardless of the outcome.

The study population consisted of 191 ADHD patients 18 and older at 71 locations in Japan. There was no control population. The 50-week flexible titrated dosing treatment period was followed by a 2-week period over which doses were gradually reduced, and then a one-week follow-up period. That means the trial covered an entire year. Of the enrolled patients, 67 dropped out, mostly due to adverse events, leaving 124 patients after the trial.

A total of 830 treatment-emergent adverse events (TEAEs) were reported by 180 patients. One in five patients (34)discontinued treatment due to adverse events. The most commonly reported adverse events were somnolence, thirst, nasopharyngitis, decreased blood pressure, postural dizziness, bradycardia (abnormally slow heartbeat), malaise, constipation, and dizziness. Except for nasopharyngitis, all were considered related to the medication. There were two serious adverse events, one unrelated to the medication, the other a supraventricular tachycardia (abnormally fast heart rhythm arising from improper electrical activity in the upper part of the heart) in a patient simultaneously medicated for a preexisting condition. The patient recovered after treatment and discontinuation of GXR.

The main TEAEs resulting in Discontinuation were somnolence (nine patients), blood pressure reduction (eight patients), malaise (six patients), and bradycardia (four patients, with only one case considered severe), and postural dizziness (three patients) or dizziness(three patients).

Significant reductions in ADHD scores and improvements in executive functioning were measured across the study population following a year's GXR treatment. Again, this was not the primary aim of the trial, and double-blinded randomized controlled trials are the gold standard.

The authors concluded that "there were no new or unexpected safety concerns" and "patients who received dose-optimized GXR had improvements in multiple aspects of ADHD, including symptoms, QoL [Quality of Life], and executive functioning," but acknowledged, "There was a potential for observer bias because of the open-label nature of the study, and the findings may not be representative of real-world settings because patients with psychiatric or cardiovascular comorbidities, which are common in patients with ADHD, were excluded. In addition, there was a potential bias favoring safety and efficacy for continuing patients because those who discontinued owing to adverse events or lack of efficacy were not eligible for inclusion."

Akira Iwanami, Kazuhiko Saito, Masakazu Fujiwara, Daiki Okutsu, and Hironobu Ichikawa, "Safety and efficacy of guanfacine extended-release in adults with attention-deficit/hyperactivity disorder: an open-label, long-term, phase 3 extension study," BMC Psychiatry(2020), https://doi.org/10.1186/s12888-020-02867-8.

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New Global Estimate of Adult ADHD Prevalence: A Comprehensive Review

Adult ADHD has long been a subject of debate in the field of mental health, with previous estimates of its prevalence varying widely. To achieve a more precise understanding, an international team of researchers conducted a new umbrella review and meta-analysis, offering an updated estimate of adult ADHD rates worldwide.

A Comprehensive Approach: Reviewing 57 Studies

This large-scale analysis combined five systematic reviews and meta-analyses, incorporating data from 57 unique primary studies. Altogether, the research synthesized findings from a pooled total of over 21 million participants. This comprehensive approach provided a more accurate estimate of the global prevalence of ADHD in adults.

Key Findings: 3.1% Global Prevalence

The study concluded that the worldwide prevalence of adult ADHD is 3.1%, with a 95% confidence interval ranging from 2.6% to 3.6%. This estimate falls within the range of earlier reports but provides a more targeted understanding of the rate at which ADHD affects adults globally.

Putting the Numbers in Context

The researchers described this prevalence rate as “relatively high.” They noted that it is only slightly lower than the estimated prevalence of major mental health conditions like schizophrenia (4%) and major depressive disorder (5%)—disorders that have historically received significant attention and resources worldwide.

Moreover, the prevalence of adult ADHD is higher than that of several other well-known mental health conditions, including bipolar disorder (1%), as well as anxiety disorders such as PTSD (Post-Traumatic Stress Disorder), OCD (Obsessive-Compulsive Disorder), GAD (Generalized Anxiety Disorder), and panic disorders.

Implications for Awareness and Treatment

This updated estimate emphasizes that ADHD is a significant global mental health concern in adults, comparable to or exceeding the prevalence of other disorders that are often more widely recognized. These findings underscore the need for greater awareness, research, and treatment options for adult ADHD, which is still frequently misunderstood or overlooked in the broader discourse of mental health.

Conclusion

By providing a clearer picture of how prevalent ADHD is in adult populations around the world, this study contributes valuable data that could shape future research, policy, and clinical approaches.

November 8, 2024

Updated Analysis of ADHD Prevalence in the United States: 2018-2021

Attention-Deficit/Hyperactivity Disorder (ADHD) remains a prevalent condition among children and adolescents in the United States. A recent analysis based on the National Health Interview Survey (NHIS), conducted by the National Center for Health Statistics at the CDC, provides an updated look at ADHD prevalence from 2018 to 2021. Here’s a closer look at what the data reveals.

How the Survey Works

The NHIS is an annual survey primarily conducted through face-to-face interviews in respondents’ homes. Telephone interviews are used as a substitute in cases where travel is impractical. For each family interviewed, one child aged 3-17 is randomly selected for the survey through a computer program. Over the four years studied (2018-2021), a total of 26,422 households with children or adolescents participated.

Overall ADHD Prevalence and Age-Related Trends

The analysis found that 9.5% of children and adolescents in the United States had been diagnosed with ADHD, based on reports from family members. However, the prevalence varied significantly with age:

  • Ages 3-5: 1.5%
  • Ages 6-11: 9.6%
  • Ages 12-17: 13.4%

The increase in ADHD diagnosis with age underscores the importance of monitoring children’s developmental needs as they progress through school and adolescence.

Gender Differences: Higher Rates Among Males

The survey revealed a notable difference in ADHD prevalence between genders, with 12.4% of males diagnosed compared to 6.6% of females—nearly a two-to-one gap. This aligns with previous research indicating that ADHD is more frequently diagnosed in boys than girls, though awareness of how ADHD presents differently across genders is growing.

Family Income and ADHD Rates

Family income played a significant role in ADHD prevalence, particularly among lower-income groups:

  • Below the poverty line: 12.7%
  • Above the poverty line but less than twice that level: 10.3%
  • Above twice the poverty level: 8.5%

This pattern suggests that socioeconomic factors might influence the diagnosis and management of ADHD, with lower-income families possibly experiencing greater barriers to early diagnosis or consistent treatment.

Regional Differences Across the U.S.

Geographic location also impacted ADHD rates. Prevalence was highest in the South (11.3%), followed by the Midwest (10%), the Northeast (9.1%), and significantly lower in the West (6.9%). These variations could reflect regional differences in healthcare access, diagnostic practices, or cultural attitudes towards ADHD.

Stability Over Time

Despite these variations in demographics, the overall prevalence of ADHD remained relatively stable across the study period from 2018 to 2021, showing no significant changes by year.

What This Means for Families and Healthcare Providers

The findings from this updated analysis provide a clearer picture of ADHD’s prevalence across different demographic groups in the United States. They highlight the need for tailored approaches to diagnosis and care, taking into account factors like age, gender, income, and geographic location. With ADHD being a common condition affecting nearly 1 in 10 children, ongoing research and support for families are crucial to ensure that those with ADHD receive the care and resources they need.

Conclusion: 

This study reinforces the importance of awareness and early intervention, especially for families in underserved regions or those facing economic challenges. As clinicians and educators continue to support children with ADHD, understanding these demographic trends can help in creating more equitable access to diagnosis and treatment.

October 29, 2024

Meta-Analysis Shows No Significant Impact of Caffeine on ADHD Symptoms

Stimulant medications like methylphenidate and amphetamines are well-established treatments for reducing ADHD symptoms, making a notable difference in focus and behavior. Given that caffeine is also a stimulant, researchers have wondered whether it might offer similar benefits for managing ADHD symptoms. A recent meta-analysis conducted by a Brazilian research team sought to explore this question.

The Search for Evidence: A Limited Pool of Studies

The researchers faced an immediate challenge: there is surprisingly little research directly investigating caffeine's effects on ADHD symptoms. After a thorough review of peer-reviewed literature, they identified only four randomized controlled trials (RCTs) suitable for their analysis, encompassing a combined total of just 152 participants.

The limited number of studies—and participants—meant that the meta-analysis was not as robust as the research team might have hoped. However, they proceeded to examine the available data to determine whether caffeine showed any measurable benefit over a placebo.

Findings: Minimal Impact, No Statistical Significance

The results of the meta-analysis showed a slight decrease in ADHD symptoms among those who consumed caffeine compared to those given a placebo. However, this reduction was not statistically significant. The small sample size likely played a role in this outcome, making the study underpowered. Even if future studies with larger groups of participants were to show statistical significance, the observed effect size would likely remain too small to be clinically meaningful.

Interestingly, the four trials included in the meta-analysis showed very little variation in their findings. Each study slightly favored caffeine over placebo, but none came close to achieving statistical significance.

Conclusion: Caffeine Is Not a Substitute for ADHD Medications

Ultimately, the researchers concluded that “overall, the totality of the evidence suggests no significant benefit of caffeine over placebo in the treatment of children with ADHD.” The findings indicate that while caffeine might produce a slight reduction in symptoms, it is not an effective alternative to established ADHD treatments like methylphenidate or amphetamines.

This study highlights the importance of relying on proven medications for ADHD management rather than seeking alternatives that lack substantial evidence. While caffeine might offer a slight stimulant effect, it falls short of delivering the therapeutic benefits needed for those with ADHD to manage their symptoms effectively. For clinicians, parents, and individuals with ADHD, these results underscore the value of evidence-based treatments in improving quality of life and daily functioning.

October 28, 2024