August 12, 2024

Meta-analysis Finds Quality of Life Improvements Associated with ADHD Medications

Quality of life (QoL) is defined as a person’s satisfaction with their life, measured across several dimensions including psychological, social, health, biological, and economic well-being. For adults, these are usually self-reported. QoL for children and adolescents is usually reported by parents.  

Medications for ADHD include stimulants (methylphenidate and amphetamines) and non-stimulants (e.g., atomoxetine, clonidine, guanfacine, viloxazine). As QoL is related to ADHD symptoms’ severity, management of ADHD via medication could improve not only core symptoms but also QoL in people with ADHD.  

Noting the absence of meta-analytic evidence on the effects of ADHD medications on QoL, an international research team conducted a systematic review and meta-analysis of parallel or cross-over randomized clinical trials (RCTs) to estimate the effects of ADHD medication on QoL. They also performed secondary analyses to see if these effects differed in children and adolescents versus adults, as well as by class of medications, and if they were moderated by length of treatment. 

Meta-analyses of four RCTs with a combined total of 950 participants with ADHD (45% adults) found a medium effect size improvement among those receiving amphetamines by comparison with those receiving placebo. There was no sign of publication bias, but there was wide variation (heterogeneity) in effect size estimated among the studies.  

Meta-analysis of four RCTs with a combined total of 1,094 participants with ADHD (57% adults) found a small-to-medium effect size improvement among those receiving methylphenidate by comparison with those receiving placebo. Again, there was no sign of publication bias, but wide variation in effect sizes among the studies. 

Due to lack of sufficient data, the team could not explore whether length of treatment affected the results, or if there were differences between children/adolescents and adults. 

Finally, a meta-analysis of eleven RCTs with a combined total of 3,344 participants with ADHD (63% adults) likewise found a small effect size improvement among those taking atomoxetine compared with those receiving placebo. Once again, there was no sign of publication bias, but wide variation in effect sizes among the studies. 

The team was able to establish that for atomoxetine treatment, length of intervention – the studies ranged from 6 to 24 weeks – had no significant moderating effect. Similarly, they found no significant differences in effect on children and adolescents versus adults.  

A single RCT evaluating modafinil treatment in adults found no improvements at any dose, whereas a single RCT testing non-stimulant guanfacine reported a medium effect size improvement in QoL.  Modafinil is not FDA approved for ADHD but is sometimes used as a last resort if other treatments fail.

The team concluded that the FDA approved medications for ADHD were significantly more efficacious than placebo in improving QoL in people with ADHD.  The improvements in Q0L were, however, smaller than what has been found for improvements is the symptoms of ADHD (inattention, hyperactivity, impulsivity).  More work is needed to detect differences by age and length of treatment. 

Alessio Bellato, Nadia J. Perrott, Lucia Marzulli, Valeria Parlatini, David Coghill, and Samuele Cortese, “Systematic Review and Meta-Analysis: Effects of Pharmacological Treatment for Attention-Deficit/Hyperactivity Disorder on Quality of Life,” Journal of the American Academy of Child & Adolescent Psychiatry (2024), https://doi.org/10.1016/j.jaac.2024.05.023

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ADHD medication and risk of suicide

ADHD medication and risk of suicide

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 ..."

December 13, 2021

How Effective and Safe are Stimulant Medications for Older Adults?

How effective and safe are stimulant medications for older adults?

Older adults are at greater risk for cardiovascular disease. Psychostimulants may contribute to that risk through side effects, such as elevation of systolic blood pressure, diastolic blood pressure, and heart rate.

On the other hand, smoking, substance abuse, obesity, and chronic sleep loss - all of which are associated with ADHD - are known to increase cardiovascular risk, and stimulant medications are an effective treatment for ADHD.

So how does this all shake out? A Dutch team of researchers sets out to explore this. Using electronic health records, they compared all 139 patients 55 years and older at PsyQ outpatient clinic, Program Adult ADHD, in The Hague. Because a principal aim of the study was to evaluate the effect of medication on cardiovascular functioning after first medication use, the 26 patients who had previously been prescribed ADHD medication were excluded from the study, leaving a sample size of 113.

The ages of participants ranged from 55 from 79, with a mean of 61. Slightly over half were women. At the outset, 13 percent had elevated systolic and/or diastolic blood pressure, 2 percent had an irregular heart rate, 15 percent had an abnormal electrocardiogram, and 29 percent had some combination of these (a "cardiovascular risk profile"), and 21 percent used antihypertensive medication.

Three out of four participants had at least e comorbid disorder. The most common are sleep disorders, affecting a quarter of participants, and unipolar mood disorders (depressive or more rarely manic episodes, but not both), also affecting a quarter of participants.

Twenty-four patients did not initiate pharmacological treatment. Of the 89 who received ADHD medication, 58 (65%) reported positive effects, and five experienced no effect. Thirty-eight (43%) discontinued ADHD medication while at the clinic due to lack of effect or to side effects. The most commonly reported positive effects were enhanced concentration, more overview, less restlessness, more stable mood, and having more energy. The principal reasons for discontinuing medication were anxiety/depression, cardiovascular complaints, and lack of effect.

Methylphenidate raised heart rate and lowered weight, but had no significant effect on systolic and diastolic blood pressure. Moreover, there was no significant correlation between methylphenidate dosage and any of these variables, nor between methylphenidate users taking hypertensive medication and those not taking such medication. There was no significant difference in systolic or diastolic blood pressure and heart rate before and after the use of methylphenidate among patients with the cardiovascular risk profiles.

Systolic blood pressure rose in ten out of 64 patients, with two experiencing an increase of at least 20 mmHg. It descended in five patients, with three having a decrease of at least 20 mmHg. Diastolic blood pressure rose by at least 10 mmHg in four patients, while dropping at least 10 mmHg in five others.

The authors concluded "that the use of a low dose of ADHD-medication is well tolerated and does not cause clinically significant cardiovascular changes among older adults with ADHD, even among those with an increased cardiovascular risk profile. Furthermore, our older patients experienced significant and clinically relevant improvement of their ADHD symptoms using stimulants, comparable with what is found among the younger age group," and that "the use of methylphenidate may be a relatively safe and effective treatment for older adults with ADHD, under the condition that all somatic complaints and especially cardiovascular parameters are monitored before and during pharmacological treatment."

Yet they cautioned that "due to the observational nature of the study and the lack of a control group, no firm conclusions can be drawn as to the effectiveness of the stimulants used. ... Important factors that were not systematically reported were the presence of other risk factors, such as smoking, substance (ab)use, aspirin use, and level of physical activity. In addition, the response to medication was not systematically measured"

December 21, 2021

How do Stimulants Modulate the Brain to Improve ADHD Symptoms?

How do Stimulants Modulate the Brain to Improve ADHD Symptoms?

The stimulants methylphenidate and amphetamine are well known for their efficacy in treating symptoms of ADHD in both youth and adults.   Although these medications have been used for several decades, relatively little is known about the mechanisms of action that lead to their therapeutic effect.    

New data about the mechanism comes from a meta-analysis by Katya Rubia and colleagues. They analyzed 14 functional magnetic resonance imaging (fMRI) data sets comprising 212 youth with ADHD.  Each of these data sets assessed the short-term effects of stimulants on fMRI-assessed brain activations. In the fMRI paradigm, ADHD and control participants are asked to do a neurocognitive task while the activity of their brains is being measured. Dr. Rubia and colleagues analyzed data from fMRI assessments of time discrimination, inhibition, and working memory, each of which is known to be deficient in ADHD patients.    

The meta-analysis found that the most consistent brain activations were seen in a region comprising the right inferior frontal cortex(IFC) and insula, even when the analysis was limited to previously medication-naïve patients. The implicated region of the brain is known to mediate cognitive control, time estimation, and attention.  Dr.Rubia also notes that other studies show that the IFC/Insula is needed for updating information and allocating attention to relevant stimuli.  

Another region implicate by the meta-analysis was the right putamen, a region that is rich in dopamine transporters. This finding is consistent with the fact that the dopamine transporter is the main target of stimulant medications.    

What is the potential clinical implication of these findings?  As Dr. Rubia and colleagues note, it is possible that the fMRI anomalies they identified could be used as a biomarker for ADHD or a biomarker to select patients who should respond optimally to stimulant medication. Although fMRI cannot be used as a clinical tool at this time, research of this sort is opening up new horizons for how we understand the etiology of ADHD and the mechanisms whereby medications exert their effects.

April 21, 2021

Patterns of Child and Adolescent Psychiatric Admissions During COVID-19: Key Insights from Clinical Data

A recent study from Istanbul sheds light on how psychiatric admissions and diagnoses changed during the first few months of the pandemic compared to previous periods, offering critical insights for parents, clinicians, and policymakers. 

This study, conducted by a team of researchers led by Ozalp Ekinci, examined psychiatric admissions among children and adolescents during 2019 and 2020. 

By looking at diagnosis rates for various psychiatric conditions, the researchers aimed to pinpoint shifts in the mental health landscape as a direct response to the pandemic.

Findings: A Closer Look at Diagnosis Patterns

The analysis revealed several notable trends in psychiatric diagnoses among children and adolescents:

  1. Autism Spectrum Disorder (ASD): ASD diagnoses were notably higher in the early pandemic phase (6.4% in Group A) compared to the same period in the previous year (3.6%). This increase could reflect heightened stress or changes in routines that may have exacerbated underlying symptoms, leading to more frequent clinical presentations.
  2. Obsessive-Compulsive Disorder (OCD) and Tic Disorders: OCD and tic disorder diagnoses also saw a rise, increasing from 1.7% in 2019 to 2.9% during the pandemic’s onset. It’s possible that pandemic-driven anxieties and hygiene concerns, as well as disruptions to typical routines, may have worsened symptoms in those predisposed to OCD and similar disorders.
  3. Intellectual Disability (ID): Diagnoses for ID rose from 2.1% (Group C) to 3.7% (Group A). This increase highlights the challenges faced by children with developmental and intellectual disabilities, who may have experienced heightened difficulty adapting to the many changes imposed by the pandemic.
  4. Attention-Deficit Hyperactivity Disorder (ADHD): ADHD diagnoses were significantly higher in the pandemic phase (59.8% for Group A vs. 49.7% for Group B). With altered school structures, remote learning, and restricted socialization, ADHD symptoms could have been amplified, making it harder for children to concentrate and adhere to routines.
  5. Depression: Depression diagnoses also saw a rise (4.1% in Group A vs. 2.2% in Group C). Isolation, disruption of daily activities, and reduced social interactions likely contributed to increased depressive symptoms, particularly in adolescents who rely heavily on peer support.
  6. Conduct Disorder (CD): Interestingly, CD diagnoses were lower during the pandemic phase compared to pre-pandemic levels (3.6% in Group A vs. 6.4% in Group B). The reduction in face-to-face interactions and less exposure to traditional school settings may have lessened some of the typical triggers associated with conduct-related issues.
Implications

This study’s findings highlight some key takeaways that can guide mental health support efforts for children and adolescents:

  1. Increased Need for Early Support in Neurodevelopmental Disorders: The rise in ASD and ADHD diagnoses points to the need for specialized support in times of crisis, particularly for children who depend on routine and structure. Families and educators should work to create consistent environments that help manage symptoms.
  2. Addressing Pandemic-Induced Anxiety: With heightened cases of OCD and tic disorders, it’s clear that the pandemic’s emphasis on cleanliness and health may have intensified anxiety-driven behaviors. Future mental health responses should include strategies to manage health-related fears and equip children with coping skills.
  3. Supporting Emotional Resilience in Adolescents: Depression was notably higher among young people during the pandemic onset, suggesting a critical need for access to counseling and peer support, especially in times of isolation. Developing robust virtual mental health resources and promoting mental well-being in schools can help support children and adolescents both in and out of school.
  4. Recognizing the Complexity of Behavioral Changes: The drop in conduct disorder diagnoses during the pandemic suggests a link between behavioral disorders and social settings. Understanding these dynamics could lead to more tailored interventions that account for environmental factors impacting behavior.
Conclusion: 

As we continue to see the effects of the COVID-19 pandemic on mental health, studies like this one serve as important reminders of the unique mental health needs of young people. Supporting children and adolescents through proactive and targeted mental health services—especially during times of crisis—will be crucial to fostering resilience and well-being in future generations.

November 19, 2024

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