April 29, 2024

Updated Meta-analysis Supports Efficacy of Guanfacine in Treating ADHD

Guanfacine is a non-stimulant medication for ADHD. It is an Alpha-2 agonist that targets and excites receptors in the prefrontal cortex of the brain, the region that governs executive functions such as judgment, decision making, planning, and response suppression. These functions tend to be sub-optimal in ADHD.

Most treatment guidelines recommend stimulants as the preferred treatment for ADHD, because they respond faster, and studies show they have higher efficacy in reducing symptoms. But for individuals for whom treatment with stimulants is subpar, guidelines recommend non-stimulants as second-line treatment.

Previous meta-analyses have focused on efficacy among children and adolescents with ADHD. This meta-analysis, by a Chinese study team, expanded its reach to not only update the former, but also include studies of adults.

The team’s systematic search of the medical literature for double-blind randomized controlled trials (RCTs) identified eleven that could be combined for meta-analysis. With only a single study of efficacy for adults, however, no meta-analysis could be performed specific to persons 18 and older.

Meta-analysis of all eleven studies with a combined total of 2,623 participants found guanfacine to be roughly 75% more effective than placebo for reducing ADHD symptoms. Variation between studies (heterogeneity) was low. There was no sign of publication bias.

Breaking that down by length of time on guanfacine found no evidence of a dose-response effect, however. In fact, participants with less than ten weeks of treatment (seven RCTs, 1,771 participants) outperformed those with longer periods of treatment (four RCTs, 852 participants) with a narrow overlap in the 95% confidence limits.

The outcomes were also sensitive to the ADHD symptom scale used. Meta-analysis of RCTs using the Clinical Global Impression of Improvement treatment response score (four studies, 850 participants) reported no significant improvement, while RCTs relying on ADHD-Rating-Scale-IV (six studies, 1,128 participants) reported a significant improvement, but without providing a standardized effect size.

Finally, a meta-analysis of ten RCTs with a combined total of 2,273 persons found a 23% increase in treatment-emergent adverse events for guanfacine relative to placebo. The three most common such events in the guanfacine group were somnolence (38.6%), headache (20.5%), and fatigue (15.2%).

Sijie Yu, Sihao Shen, and Ming Tao, “Guanfacine for the Treatment of Attention-Deficit Hyperactivity Disorder: An Updated Systematic Review and Meta-Analysis,” Journal of Child and Adolescent Psychopharmacology (2023), https://doi.org/10.1089/cap.2022.0038.

Related posts

No items found.

Swedish Nationwide Population Study Finds Strong Association Between ADHD and Sleep Disorder Diagnoses and Sleep Medication Prescriptions

There has been consistent evidence of an association between ADHD and subjectively reported sleep problems even in patients not medicated for the disorder. There have also been studies using wrist-worn actigraphy (a wrist watch-like device that measures gross motor activity) and sleep lab-based polysomnography that measure objective sleep parameters. 

What has been missing are large population-based cohort studies to explore the prevalence rates of different sleep disorders and medical prescriptions in ADHD. 

Methods Used: 

Sweden has a single-payer health insurance system and a series of national population registers that track virtually its entire population. Using the Swedish Total Population Register, a local research team created a cohort of all 6,470,658 persons born between 1945 and 2008. They linked this to the Swedish National Patient Register, which includes inpatient hospitalizations from 1975 to 2013, and outpatient specialist diagnoses from 2001 to 2013, to identify diagnoses of sleep disorders. They also linked to the Prescribed Drug Register, covering 2005 to 2013, to identify prescriptions for sleep medications. 

Summary of Findings: 

Overall, persons with ADHD were eight times more likely to be diagnosed with any sleep disorder relative to normally developing peers. Broken down by age, adolescents with ADHD were 16 times more likely to receive such diagnoses, young adults (18-30) twelve times more likely, children and mid-age adults (31-45) eight times more likely, and older adults six times more likely. 

Broken down by specific sleep disorder diagnoses, relative to normally developing peers, persons with ADHD were: 

  • Five times more likely to have sleep terrors and seven times more likely to have nightmares. 
  • Six times more likely to sleepwalk. 
  • Seven times more likely to have restless leg syndrome. 
  • Sixteen times more likely to have insomnia. 
  • Nineteen times more likely to have disorders of sleep/wake schedule (circadian rhythms). 
  • Twenty times more likely to have hypersomnia (excessive sleeping). 
  • Over seventy times more likely to exhibit narcolepsy (daytime sleepiness) and cataplexy (sudden loss of muscle tone leading to collapse). 

As for sleep medication, relative to normally developing peers, persons with ADHD were: 

  • Seven times more likely to be prescribed the hypnotic zolpidem (Ambien). 
  • Eight times more likely to be prescribed the hypnotic zopiclone or the antihistamine propriomazine. 
  • Ten times more likely to be prescribed the sedative and hypnotic zaleplon (Sonata). 
  • Fourteen times more likely to be prescribed any sleep medication. 
  • 37 times more likely to be prescribed melatonin, the body’s natural sleep-inducing hormone, which is a prescription medication in Europe. 

Conclusion: 

The team concluded, “Our findings also suggest that greater clinical attention should be directed towards addressing sleep problems in individuals with ADHD. This entails implementing proactive measures through sleep education programmes and providing both pharmacological and non-pharmacological approaches such as cognitive behavioural therapy and parental sleep training.” 

December 12, 2024

Taiwanese Population Study Finds Strong Association Between Cleft Lip and Palate and Subsequent ADHD

Congenital cleft lip and palate (CCLP) are birth defects associated with genetic and environmental factors. The latter include heavy maternal consumption of alcohol and fetal exposure to retinoid drugs derived from vitamin A. 

Methods:

Taiwan has an island-wide single-payer health insurance system that reaches over 99% of the population. To explore the relationship between CCLP and various psychiatric disorders including ADHD, a Taiwanese study team used the island’s National Health Insurance Research Database to identify all 1,158 children and adolescents with CCLP during a ten-year period. They matched them ten-to-one with 11,580 age and sex-paired controls without CCLP. 

Summary of Results:

Further adjusting for demographic data (income, residence) and family history of major psychiatric disorders, children and adolescents with CCLP were more than seven times more likely to be diagnosed with ADHD during the follow-up period than controls. Patients with both cleft palate and cleft lip were more than nine times more likely to be subsequently diagnosed with ADHD than controls. 

Patients with CCLP were also six times more likely to be diagnosed with autism spectrum disorder and more than seven times as likely to be diagnosed with schizophrenia as non-CCLP controls. They were also more likely to be diagnosed with bipolar disorder or major depressive disorder, but these results did not reach statistical significance. 

Conclusion:

This study highlights a significant association between congenital cleft lip and palate (CCLP) and an increased risk of developing ADHD, with CCLP patients being more than seven times as likely to be diagnosed with the disorder. Additionally, CCLP was linked to a higher prevalence of other psychiatric conditions, including autism spectrum disorder and schizophrenia. These findings underscore the importance of monitoring mental health in individuals with CCLP and call for further research into the risk factors connecting these birth defects with psychiatric disorders.

 

December 9, 2024

Effect of Physical Activity on Attention in School-age Children with ADHD: Systematic Review and Meta-Analysis

Overview

Attention is a critical determinant of academic achievement, influencing domains such as language, literacy, and mathematics. To explore whether physical activity can improve attention in children with ADHD, an international team conducted a meta-analysis of peer-reviewed studies. The goal was to evaluate the impact of various physical activity regimens on attention-related outcomes in this population.

Methods

The researchers performed a comprehensive search of the medical literature to identify studies examining the effects of physical activity on attention in schoolchildren with ADHD. They included 10 studies with a total of 474 participants in their meta-analysis. The studies evaluated two main types of physical activity:

  • Mentally engaging physical activities
  • Aerobic exercise

Additionally, they examined variations based on the frequency, duration, and type of control groups used in the studies. To assess consistency, they also analyzed heterogeneity (variability of outcomes) and checked for potential publication bias.

Summary

Key findings from the meta-analysis include:

  1. Effectiveness of Mentally Engaging Activities:some text
    • Seven studies (168 participants) involving mentally engaging physical activities showed large reductions in attention problems.
    • Heterogeneity was significantly reduced for these studies.
  2. Effectiveness of Aerobic Exercise:some text
    • Three studies (306 participants) using aerobic exercise alone found no improvements in attention.
  3. Impact of Control Groups:some text
    • Studies with no intervention as a control group (4 studies, 81 participants) reported large improvements in attention problems.
    • Those comparing physical activity with other interventions (6 studies, 393 participants) found only small improvements.
  4. Frequency and Duration:some text
    • Duration of physical activity made little difference. Studies with sessions of an hour or more had slightly better outcomes, but the difference was not significant.
    • Surprisingly, lower frequency was more effective:some text
      • One to two sessions per week (7 studies, 162 participants) led to large reductions in attention problems.
      • Three or more sessions per week (3 studies, 312 participants) showed no improvement.
Conclusion

The authors concluded that mentally engaging exercise is more effective than aerobic exercise in improving attention problems in schoolchildren with ADHD. Furthermore, higher frequency and longer duration of physical activity do not necessarily yield better outcomes.

This research underscores the importance of tailoring physical activity interventions to emphasize cognitive engagement over intensity or duration. By refining strategies, educators and parents can better support children with ADHD in achieving academic success.   But take note:  given the results from controlled studies, it seems clear that if there is a positive effect of exercise, it is very small so should not replace standard treatments for ADHD.