July 8, 2021

High Dropout Rate in Six-Year Cohort Study of Medication Treatment for ADHD

Few studies have examined the safety and tolerability of ADHD medications (stimulants and atomoxetine) extending beyond six months, and none beyond a few years. A pair of Swedish neuroscientists at Uppsala University Hospital set out to explore longer-term outcomes. They conducted a six-year prospective study of 112 adults diagnosed with ADHD who were being treated with ADHD medications (primarily MPH, but also dexamphetamine and atomoxetine).


They found that at the end of that period, roughly half were still on medication, and half had discontinued treatment. There were no significant differences between the two groups in age, sex, ADHD severity, or comorbidity. The average ADHD score for the entire cohort declined to vary significantly, from a mean of 37 to a mean of 26, with less than one in a thousand odds of that being due to chance. There was also no sign of drug tolerance or a need to increase the dosage over time.
All 55 adults who discontinued treatment had taken MPH for at least part of the time. Eleven had also been treated with dexamphetamine(DEX) and 15 with atomoxetine (ATX). The average time on treatment was just under two years. Almost a third quit MPH because they perceived no beneficial effect. Since they were on average taking higher doses at discontinuation than initiation, that is unlikely to have been due to suboptimal dosage. Almost another third was discontinued for various adverse mental effects, including hyperactivity, elation, depressive moods, aggression, insomnia, fatigue, and lethargy. Another one in eleven quit when they lost contact with the prescribing physician. In the case of ATX, almost half quit because of what they perceived as adverse mental effects.


Among the 57 adults who remained on medication, four out of five reported a strong beneficial effect. Only two reported minimal or no effect. Compared with the group that discontinued, the group that remained on medication was far more likely to agree with the statements, "My quality of life has improved," and "My level of functioning has improved." Yet, as the authors caution, it is possible "that the subjects' subjective ratings contained a placebo-related mechanism in those who are compliant with the medication and pursue treatment over time." The authors reported that there were no significant differences in ADHD scores or ADHD severity between the group that quit and the group that remained on medication, even though, on average, the group that quit had been off medication for four years at follow-up.


We cannot explain why the patients who quit treatment showed similar levels of ADHD symptoms to those who continued treatment.  It is possible that some patients remit symptoms over time and do not require sustained treatment.  But we must keep in mind that there was a wide range of outcomes in both groups. Future work needs to find predictors of those who will do well after treatment withdrawal and those who do not.


Any decision on whether to maintain a course of medication should always weigh expected gains against adverse side effects. Short of hard evidence of continuing efficacy beyond two years, adverse events gain in relative importance. With that in mind, it is worth noting that this study reports that among those who remained on MPH, many reported side effects. More than a quarter complained of decreased appetite, one in four of dry mouth, one in five of anxiousness and increased heart rate, one in six of decreased sexual desire, one in nine of depressed mood, and one in eleven of insomnia.


This study breaks important ground in looking at the long-term effects of medication. It reaffirms findings elsewhere of the efficacy of ADHD medications. But contrary to the authors' conclusion, the data they present suggests the possibility that permanently medicating ADHD patients may not be more efficacious than discontinuation beyond a certain point, especially when balanced against adverse side effects.
But this is just one study with a relatively small sample size. This suggests a need for additional studies with larger sample sizes to pursue these questions with greater statistical reliability.

Dan Edvinsson and Lisa Ekselius, "Long-Term Tolerability and safety of Pharmacological Treatment of Adult Attention-Deficit/hyperactivity disorder," Journal of clinical psychopharmacology, vol. 38, no. 4(2018).

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Exploring the Impact of ADHD Treatment on Empathy and Narcissism

A recent study published in Alpha Psychiatry sheds light on the connection between ADHD, empathy, and narcissistic traits. Researchers aimed to evaluate how pharmacological treatments—specifically psychostimulants—affect empathy deficits and pathological narcissism in adults with ADHD. These findings could have important implications for enhancing treatment outcomes and improving social functioning.

Study Overview
The study involved 75 adult ADHD patients who were treated with either methylphenidate or atomoxetine. Researchers assessed levels of narcissistic traits and empathy using validated tools such as the Pathological Narcissism Inventory (PNI) and the Empathy Quotient (EQ). Measurements were taken before treatment and after three months of therapy.

Key Findings

  • Narcissistic Traits: Patients showed a significant reduction in grandiosity and vulnerability scores, with total PNI scores decreasing after treatment.
  • Empathy Levels: Empathy improved significantly, as reflected by higher post-treatment EQ scores.
  • Overall Impact: These changes suggest that psychostimulant treatment positively influences brain circuits related to empathy and narcissistic tendencies, potentially leading to better interpersonal relationships.

Why It Matters
Adults with ADHD often struggle with social interactions, partly due to empathy deficits and personality traits like narcissism. By addressing these challenges through psychostimulant treatment, patients may experience better social and emotional well-being. This study underscores the importance of viewing ADHD treatment as not just a way to manage symptoms but also a means to improve overall quality of life.Takeaway
Effective ADHD treatment goes beyond managing attention and hyperactivity. By improving empathy and reducing narcissistic traits, psychostimulants can foster healthier relationships and enhance social functioning. This research highlights the need for comprehensive care that considers the broader psychological and interpersonal effects of ADHD.

February 4, 2025

Meta-analysis Suggests Music Training May Be a Useful Tool for Inhibition Control

According to Fosco et al. (2019), “Inhibitory control has long been considered a central neurocognitive process in ADHD, with ADHD groups typically showing medium-sized impairments relative to their typically-developing peers on common inhibition paradigms.” 

Learning to play a musical instrument requires effective coordination of physical movements and sound signals to produce music. Musical training involves repetitive practice, perfecting connections between perceptions, muscular actions, and cognition. 

Noting that listening to music activates the brain’s reward circuits in both children and adults, that “Being internally motivated during learning experiences increases learning capacity and efficiency, and this greater engagement is reflected in increased electrical brain activity following musical training,” and that “Training music in a social environment increases positive feelings of bonding through shared emotions and group synchrony,” a Montreal-based research team carried out a systematic review and meta-analysis of the peer-reviewed medical literature from 1980 to 2023 to learn what effect music training might have on inhibition control. 

Outcomes:

The team found eight randomized controlled trials (RCTs) and 14 other longitudinal studies that met search criteria, including: 

  • Music training was with neurotypical children and adolescents 
  • The experimental group was trained using music alone 
  • Studies were longitudinal, with either active or passive controls 
  • Studies included a performance-based inhibition control measure as an outcome 

Meta-analysis of all 22 longitudinal studies with a combined total of 1,734 participants yielded a small-to-medium effect size improvement in inhibitory control. Variation (heterogeneity) in outcomes between individual studies was small, and there was no sign of publication bias. Restricting the analysis to the eight RCTs with a combined total of 641 participants, however, yielded a medium-to-large effect size improvement, with negligible heterogeneity, meaning the outcome was consistent across RCTs. 

The Take-Away: The team concluded, “Music training plays a privileged role compared to other activities (sports, visual arts, drama) in improving children’s executive functioning, with a particular effect on inhibition control.”   I cannot, however, recommend this as a therapy for ADHD until RCTs show it reduces symptoms of ADHD and/or real world impairments associated with the disorder.

February 3, 2025

Population Study Finds No ADHD- or ASD- Related Benefits From Eating Organic Food During Pregnancy

Norwegian Nationwide Population Study Finds No ADHD- or ASD- Related Benefits From Eating Organic Food During Pregnancy

Background:

Organic farming aims to protect biodiversity, promote animal welfare, and avoid using pesticides and fertilizers made from petrochemicals. Some pesticides are designed to target insects’ nervous systems but can also affect brain development and health in larger animals, including humans.

Many people believe organic food is healthier than conventionally produced food, which might be true for certain foods and health factors. But does eating organic food during pregnancy impact the chances of a child developing ADHD or autism spectrum disorder (ASD)?

In Norway, researchers can use detailed national health records to study these connections on a population-wide level, thanks to the country’s single-payer healthcare system and national registries.

Method:

The Norwegian Mother, Father, and Child Cohort Study (MoBa) invites parents to participate voluntarily and has a 41% participation rate. The study includes:

  • 114,500 children
  • 95,200 mothers
  • 75,200 fathers

For this research, a team tracked 40,707 mother-child pairs from children born between 2002 and 2009. They used questionnaires to measure how much organic food mothers consumed during pregnancy. ADHD and ASD symptoms in children were assessed using validated rating scales.

The final analysis included:

  • 40,586 pairs for ADHD symptoms
  • 40,117 pairs for ASD symptoms

The researchers adjusted for factors like maternal age, education, previous pregnancies, BMI before pregnancy, smoking and alcohol use during pregnancy, birth year and season, and the child’s sex.

Key Findings:
  • There was a weak connection between higher organic food consumption and fewer ADHD symptoms in children. However, this link disappeared when maternal ADHD symptoms were considered (31,411 pairs) or when the analysis was limited to siblings (5,534 pairs).
  • Similarly, weak associations between organic food and fewer ASD symptoms disappeared when focusing on siblings (4,367 pairs).
Conclusion:

The researchers concluded that eating organic food during pregnancy has no meaningful effect on the likelihood of a child developing ADHD or ASD. They stated, “The results do not indicate any clinically significant protective or harmful effects of eating organic food during pregnancy on symptoms of ADHD and ASD in the offspring. Based on these findings, we do not recommend any specific advice regarding intake of organic food during pregnancy.”

January 27, 2025