November 21, 2021

Safety of long-term methylphenidate treatment of adults with ADHD

The Comparison of Methylphenidate and Psychotherapy in adult ADHD Study (COMPAS) was a prospective, randomized multicenter clinical trial, comparing methylphenidate (MPH) with placebo in combination with cognitive-behavioral group psychotherapy or (GPT) individual clinical management (CM), the latter two being active controls. This was a year-long trial.

The German study team randomly assigned 433 participants with adult ADHD to each of the four study groups. As this was a 2 x 2 matrix trial, each study group included both one pharmacological intervention (MPH or placebo) and one psychological intervention (GPT or CM).

GPT included mindfulness training, skills for stress management, emotion regulation, and time management as well as behavioral analyses. CM sessions focused on participants' current concerns and medication.

As is usual in such trials, the number of participants decreased throughout the study as some individuals dropped out. At 13 weeks, 337 participants were still taking their study medication.

Both MPH and placebo were started at 10 mg doses, then up-titrated depending on clinical response. After 13 weeks, the mean MPH dose had risen to 50 mg, and the mean dose of placebo to 58 mg.

Safety

Among those taking MPH, 96 percent of participants reported at least one adverse event. Among those on placebo, the equivalent figure was 88 percent.

The principal adverse events occurring significantly more frequently in the MPH group were decreased appetite (22 vs. 3.8 %), dry mouth (15 vs. 4.8 %), palpitations (13 vs. 3.3 %), gastrointestinal infection (11 vs. 4.8 %), agitation (11 vs. 3.3 %), restlessness (10 vs. 2.9 %), excessive sweating, rapid heartbeat, and weight decrease (all 6.3 vs. 1.9 %).

The only adverse event that occurred significantly more frequently in the placebo group was a temporary loss of consciousness caused by a fall in blood pressure (2.4 vs. 0%).

Serious adverse events were infrequent in both groups, affecting 7.3 percent of those in the MPH group and 4.3 percent of those in the placebo group. The difference between groups was not statistically significant. There were no deaths.

While patients on MPH lost an average of 1.2 Kg during the year, those on placebo remained constant (gained 0.3 Kg). Changes in blood pressure were negligible in both groups. Average heart rate rose by 3 beats per minute in the MPH group, versus a 1 beat per minute decline in the placebo group. There were no significant differences in clinically relevant electrocardiogram abnormalities between the two treatment groups.

Turning to psychological interventions, 90 percent of participants in the GPT group and 94 percent in the CM group experienced at least one adverse event. Differences between the two groups were not statistically significant. Serious adverse events occurred in 3.9% of the GPT participants and 7.7 percent of the CN participants, but again the difference between groups was not statistically significant. There were no clinically relevant changes in weight, blood pressure, or heart rates in these groups throughout the study.

The study team found no modulating effects of either form of psychological treatment on the distribution of adverse events under MPH and placebo treatment.

The authors concluded, "adverse events were found more frequently in patients receiving MPH compared to placebo and were mostly attributable to the centrally stimulating and sympathomimetic action of MPH, including agitation, restlessness, dry mouth, decreased appetite, palpitations, tachycardia [rapid heartbeat], and hyperhidrosis [excessive sweating]. About these adverse events, a causal relationship with MPH seems likely, supported by both the pharmacological effects of MPH as well as previous safety data. ... It is important to note that patients receiving MPH in COMPAS significantly profited from the medication about the reduction of ADHD symptom load, thus the risks of adverse events have to be weighed against the clear benefits. ... Premature termination of MPH due to an adverse event as major reason occurred in less than 10 % of patients and was not statistically significantly different from placebo."

Bernhard Kis, Caroline Lücke, Mona Abdel-Hamid, Philipp Heßmann, Erika Graf, Mathias Berger, Swantje Matthies, Patricia Borel, Esther Sobanski, Barbara Alm, Michael Rösler, Wolfgang Retz, Christian Jacob, Michael Colla, Michael Huss, Thomas Jans, Ludger Tebartz van Elst, Helge H. O. Müller, Alexandra Philipsen, "Safety Profile of Methylphenidate Under Long-Term Treatment in Adult ADHD Patients - Results of the COMPAS Study," Pharmacopsychiatry (2020), https://doi.org/10.1055/a-1207-9851.

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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

Meta-analysis Finds Little or No Link Between Assisted Reproductive Technologies and ADHD

Background:

Infertility affects about one in six couples worldwide. To address this, medical experts have developed Assisted Reproductive Technologies (ART), including In Vitro Fertilization (IVF) with or without Intra-Cytoplasmic Sperm Injection (ICSI).

Some research suggests that children conceived through ART might have higher rates of intellectual disabilities, cerebral palsy, cancer, and neurological issues compared to children conceived naturally. However, studies looking at a possible link between ART and ADHD have produced mixed and conflicting results.

Until now, there hasn’t been a meta-analysis examining the connection between ART and ADHD. A South Korean research team has conducted the first systematic review and meta-analysis on this topic. Their final analysis included eight studies with a total of over ten million participants, comprising six cohort studies and two cross-sectional studies.

Method:

The research focused on two types of studies:

  1. Cohort Studies: These follow two groups (one exposed to ART and one not exposed) over time to see if a specific outcome, like ADHD, occurs.
  2. Cross-Sectional Studies: These compare the prevalence of ADHD at a single point in time between those exposed to ART and those who weren’t.

Both types of studies are observational, meaning they don’t involve controlled experiments and can be influenced by confounding factors.  So they can document interesting associations, not causality.  The studie were mostly large-scale national studies and used clinical ADHD diagnoses.

Key Findings:
  • Cohort Studies: Meta-analysis of six cohort studies, involving nearly 8 million participants, found no link between ART and ADHD. However, there was high variability (heterogeneity) in the results from individual studies.
  • Cross-Sectional Studies: Meta-analysis of two cross-sectional studies, covering over 2.3 million participants, also found no link between ART and ADHD. Heterogeneity was moderate.
  • Adjustment for Confounding: A separate analysis of three studies that adjusted for confounding factors (like socioeconomic status or parental health) involved more than 7.5 million participants. It found a very small association, with ART-conceived children being 8% more likely to develop ADHD. There was no variability among these studies.
Conclusion:

The researchers concluded that while there may be a small association between ART and ADHD, the effect is minimal, and the results are influenced by differences in study designs. They advised interpreting these findings with caution, noting, “The limited effect size and inherent heterogeneity underscore the need for cautious interpretation.”

January 24, 2025

Taiwan nationwide population study documents link between ADHD and periodontitis in adolescents

Background:

Periodontitis, commonly known as gum disease, is a condition where the gums become inflamed. If untreated, it can cause the gums to pull back from the teeth, exposing their base, which may eventually lead to loose teeth or tooth loss. While this condition mostly affects adults, it’s also common among teens who don’t floss or brush their teeth properly.

Until now, only a few small studies have looked at a possible link between ADHD and gum disease. A team in Taiwan recently conducted a nationwide study to explore this connection.

Taiwan has a universal health insurance program, introduced in 1995, that provides medical care to nearly all (99.7%) residents. The Taiwan National Health Research Database collects and oversees all insurance claims, making it an excellent resource for large-scale studies.

Methods:

The researchers used the database to identify teens aged 12 to 19 with ADHD (diagnosed by a psychiatrist) who had no history of gum disease between 2001 and 2011. These teens made up the ADHD group. They matched each ADHD participant with four teens who didn’t have ADHD or gum disease, creating a control group. The groups were matched by age, gender, enrollment date, family income, place of residence, and other health conditions (like obesity, diabetes, smoking, depression, and substance use).

All diagnoses of gum disease were confirmed by board-certified dentists.

The study included:

  • 16,211 teens with ADHD
  • 162,110 matched controls
Key Findings:
  • Teens with ADHD were 2.3 times more likely to develop gum disease than those in the control group without ADHD.
  • There were no significant differences between boys and girls or among teens from different income levels (low, medium, or high).
  • ADHD medications, mainly methylphenidate, didn’t affect the likelihood of developing gum disease. This was true for both short-term and long-term users compared to non-users.
Conclusion:

The researchers concluded that teens with ADHD have a higher risk of developing gum disease later on, even after accounting for other risk factors like smoking, diabetes, and depression. They stated, “ADHD is an independent risk factor for developing periodontitis.”

January 23, 2025