August 15, 2024

Meta-analysis Finds Strong Placebo Response in Treatment of ADHD, Mid-range Among Nine Neurological Disorders

A placebo is a pill that does not contain any active medication.  It is given to patients who form the control group in clinical trials.  Comparing the effects of a treatment with placebo is essential because some patients will improve with the passage of time and some will get better due to the expectation of benefit they have from being enrolled in a clinical trial.

In studies of psychiatric conditions, patients in placebo groups typically show improvement. This can be induced by combinations of hope, suggestion, expectation, and consumption of what are presented as medications. It is reinforced by the context of receiving compassionate care from others, with supportive conversations. 

A 2005 study found that placebo response is unequally distributed across psychiatric disorders, but did not address several disorders (including bipolar disorder) examined in the present meta-analysis conducted by a German research team. 

Using only high-quality randomized clinical trials (RCTs) across major psychiatric diagnoses, the team quantified differences in the change of disorder symptoms within placebo groups.  

They selected nine common and clinically significant psychiatric conditions: major depressive disorder (MDD), mania (bipolar disorder), schizophrenia, obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), generalized anxiety disorder (GAD), panic disorder, posttraumatic stress disorder (PTSD), and social phobia. For each of these, they selected the ten most recent high-quality RCTs of medicationsfor meta-analysis. 

Of the ninety included RCTs, the team only looked at placebo groups. Because RCTs for the different diagnoses used differing established psychopathology rating scales, standardized pre-post effect sizes were used to compare outcomes across diagnoses. 

Meta-analysis of the ten ADHD RCTs with a combined total of 1,189 participants reported large effect size improvements in symptoms, with no variation (heterogeneity) across RCTs and no sign of publication bias. 

By contrast, the placebo effect size improvements in symptoms of major depressive disorder (10 RCTs, 1,598 participants) and generalized anxiety disorder (10 RCTs, 1,457 participants) were very large, well above those for ADHD, and with no overlap of 95% confidence intervals. 

At the other end of the spectrum, the placebo effect size improvements in symptoms of schizophrenia (10 RCTs, 888 participants) were moderate, well below those for ADHD, and with no overlap of 95% confidence intervals. 

There were absolutely no indications of publication bias. 

The team noted, “In all diagnoses, there were improvements in symptom severity during placebo treatment (ie, the lower limit of the 95% CIs of the pooled pre-post placebo effect sizes were >0).” Although they stated, “The large and robust improvements observed in ADHD studies have not been reported to our knowledge.”  they seemed to have missed this article by me and my colleagues:  https://pubmed.ncbi.nlm.nih.gov/34232582/

They also concluded, “Comparing the courses of different disorders under placebo indirectly may assist in understanding disease etiology, possibly providing insights into the proportionate influence of organic and psychogenic factors. Conditions with presumed substantial hereditary and biological components, such as schizophrenia, exhibited modest placebo responses in our analysis. Conversely, disorders with potentially less biological contribution, eg, depression and GAD, showed stronger responses. Our study may serve as an initial framework for incorporating the comprehensive insights derived from placebo groups of controlled trials into the etiopathogenetic exploration of mental illnesses.”

Yanli Zhang-James, John W.S. Clay, Rachel B. Aber, Hilary M. Gamble, Stephen V. Faraone,
Post–COVID-19 Mental Health Distress in 13 Million Youth: A Retrospective Cohort Study of Electronic Health Records,
Journal of the American Academy of Child & Adolescen

Tom Bschor, Lea Nagel, Josephine Unger, Guido Schwarzer, and Christopher Baethge, “Differential Outcomes of Placebo Treatment Across 9 Psychiatric Disorders: A Systematic Review and Meta-Analysis,” JAMA Psychiatry (2024), https://doi.org/10.1001/jamapsychiatry.2024.0994

Faraone, S. V., Newcorn, J. H., Cipriani, A., Brandeis, D., Kaiser, A., Hohmann, S., Haege, A. & Cortese, S. (2021). Placebo and nocebo responses in randomised, controlled trials of medications for ADHD: a systematic review and meta-analysis. Mol Psychiatry 27, 212-219.

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South Korean Population Study Finds Child ADHD Impacts Maternal, but Not Paternal, Mental Health

Given the persistence of ADHD and its adverse effects on children and adolescents, one might expect caregivers to face greater parenting challenges, with potential effects on their own mental health. 

To what extent do parenting stress, depression, and – at the extreme – even suicidal ideation manifest themselves among caregivers of ADHD patients as opposed to caregivers of children and adolescents without ADHD? 

A pair of Korean researchers made use of their country’s single-payer health insurance system, which maintains records on virtually the entire population, to perform a nationwide population study. They used data from the Korean National Health and Nutrition Examination Surveys (KNHANES) covering the decade from 2011 to 2020. KNHANES is an annual survey using a sophisticated sampling design conducted by the Korean Ministry of Health and Welfare to represent the entire population of South Korea. 

The analysis included 14,428 individuals who had children younger than 19 at the time of participation. All were asked whether their child had ever been diagnosed with ADHD by a physician. The mental health problems of the parents were assessed in terms of perceived stress, depressive symptoms, and suicidality. 

Of the 14,428 participants, 8,298 (57.5 %) were mothers and 6,130 (42.5 %) were fathers. Of the mothers, 116 (1.4 %) had a child with ADHD, and of the fathers, 86 (1.4 %) had a child with ADHD. 

The researchers adjusted for the following confounders: age of caregiver, education level, household income, area of residence, employment status, alcohol consumption, smoking status, cohabitation status, number of children, and child’s age. 

After adjustment, mothers of ADHD patients fared significantly worse than mothers of typically developing children on all three categories of mental health problems. They were 67% more likely to report higher stress, three times as likely to report symptoms of depression, and 2.5 times more likely to report suicidal ideation.  

Yet that pattern did not carry over to fathers, where there was no significant difference in mental health indicators between fathers of children with ADHD and fathers of children without ADHD. 

The authors concluded, “Parents of children with ADHD, especially mothers, need community support and public health attention to help alleviate their mental health problems.” 

 

February 19, 2025

South Korean Nationwide Population Study Finds ADHD Diagnosis Associated With Greater Odds of Subsequent Diagnosis of Major Psychiatric Disorders

Background: 

ADHD is commonly accompanied by psychiatric comorbidities that complicate its diagnosis and treatment. Roughly two out of three affected children and adolescents have one or more comorbid psychiatric disorder. 

Because the peak age of ADHD onset is typically a decade or more earlier than those for schizophrenia, depressive disorder, or bipolar disorder, it is essential to explore these comorbidities over an extended period. Populations studies help researchers identify broader patterns and trends within an entire population and includes adults as well as children. This type of study provides unique insights into the population at large, rather than a sample group.

In earlier studies the maximum follow-up period was twelve years, insufficient in view of the roughly ten years between onset of ADHD and onset of major psychiatric disorders. Also, previous nationwide population studies have included less than 150,000 participants. 

The Study:

This study, relying on data from South Korea’s universal single-payer health insurance system, included over one and a half million individuals. Persons previously diagnosed with depression, bipolar disorder, tic disorder, or schizophrenia were excluded. 

382,434 individuals had been diagnosed with ADHD, while 1,169,279 were without an ADHD diagnosis.  

Propensity score matching ensured that potential confounders, both sociodemographic and clinical, were equalized for the ADHD and control groups. After matching, there were 353,898 individuals in each group. 

After these adjustments, individuals in the ADHD group were at least an order of magnitude more likely to subsequently be diagnosed with  psychiatric disorders than their peers without an ADHD diagnosis: 

  • Almost eleven times more likely to be diagnosed with depressive disorder. 
  • More than twelve times as likely to be diagnosed with bipolar disorder. 
  • Over thirteen times more likely to be diagnosed with schizophrenia. 

Conclusion:

The Korean study team concluded, “Overall, our findings suggest that upon prolonged examination, the risk of subsequent diagnoses of other psychiatric disorders in individuals with ADHD appears to be higher than that reported previously. … Therefore, patients with ADHD should be carefully screened for the presence of other psychiatric symptoms on a regular basis from an earlier age … It is advisable to have a follow-up period extending beyond 10 years to sufficiently identify the occurrence of comorbid disorders in patients with ADHD.” 

February 18, 2025

NEWS STUDY: Focus Group Study of Primary Teachers' Perceptions of Children with ADHD who Struggle Socially

Children with ADHD often face challenges in social interactions, leading to long-term consequences if not properly addressed. While various interventions exist, many fail to consider the broader social context in which these children interact. A recent study conducted in Bergen, Norway, explored how primary school teachers perceive their role in supporting children with ADHD who struggle socially and the strategies they use to assist them.

Investigating Teacher Perspectives

Researchers conducted semi-structured interviews with five focus groups of primary school teachers. Using reflexive thematic analysis, they identified two major themes:

  1. Understanding Individual Needs in Context – Teachers emphasized that every child is unique, and ADHD should not define a student's social struggles. They highlighted the importance of considering the child’s specific social challenges within their broader environment.
  2. Adapting Strategies Through Continuous Assessment – Teachers described their work as a dynamic and flexible process, adjusting their approaches based on the child's evolving needs. This included providing subtle background support as well as direct guidance in social interactions.
A Personalized Approach to Social Support

Rather than relying on standardized interventions, teachers tailored their strategies to foster an inclusive and supportive social environment. Their methods included both active participation in social situations and behind-the-scenes efforts to encourage peer inclusion and understanding.

Rethinking ADHD and Social Development

This study underscores the need to move beyond labels and recognize children with ADHD as individuals with distinct social needs. Teachers play a crucial role in shaping these children’s experiences, using flexible and personalized approaches to promote positive social interactions. By integrating social context and individualized support, educators can help children with ADHD build meaningful connections and navigate their social world more effectively.

February 12, 2025