Potential cardiovascular risks are associated with ADHD medication. Prevalence of ADHD and the increasing use of medication to treat it, require a discussion. Although the short-term effectiveness of ADHD medications has been demonstrated, the long-term cardiovascular effects remain unclear. Observational studies show mixed findings regarding the association between ADHD medication and serious cardiovascular outcomes.
There are knowledge gaps and a lack of comprehensive understanding of the cardiovascular risks associated with ADHD medication use. Given the rising trend in long-term medication usage it is important to examine how cardiovascular risk may vary. There maybe other factors such as type of medication, type of cardiovascular disease, age, and sex requiring a deeper insight.
The study was conducted to assess the association between cumulative use of ADHD medication and the risk of cardiovascular disease.
Who Were The Study Participants?
The study utilized data from several Swedish nationwide registers, linked through unique personal identification numbers. The National Inpatient Register provided inpatient diagnoses since 1973 and outpatient diagnoses since 2001. Whilst the Swedish Prescribed Drug Register contained information on dispensed medications since July 2005, including drug identity.
How Was The Study Designed?
The study was a nested case-control study conducted in Sweden, involving individuals aged 6 to 64 years. They received an incident diagnosis of ADHD or ADHD medication dispensation between January 1, 2007, and December 31, 2020. The diagnosis of ADHD was identified from the National Inpatient Register using the ICD-10 code F90. Incident ADHD medication dispensation was identified from the Swedish Prescribed Drug Register. Baseline for the study was defined as the date of incident ADHD diagnosis or ADHD medication dispensation, whichever came first. The cohort was followed until the case index date (the date of cardiovascular disease diagnosis), death, migration, or the study end date (December 31, 2020), whichever came first.
During follow-up, specific conditions such as ischemic heart diseases, cerebrovascular diseases, hypertension, heart failure, arrhythmias, thromboembolic disease, arterial disease, and other forms of heart disease were identified. Each case’s index date was assigned as the date of their CVD diagnosis. Up to 5 controls without CVD were randomly selected for each case. The matching criteria included age, sex, and calendar time so that cases and controls had the same duration of follow-up.
ADHD Medications Under Consideration
The main exposure in the study was the cumulative duration of ADHD medication use. All approved medications in Sweden during the study period were included:
Stimulants such as
- Methylphenidate,
- Amphetamine,
- Dexamphetamine, and
- Lisdexamfetamine,
Non-stimulants like
- Atomoxetine and
- Guanfacine.
A validated algorithm was used to estimate treatment duration from free text in prescription records. The cumulative duration of ADHD medication use was determined by summing all days covered by medication from baseline to 3 months prior to the index date. The exclusion of the last 3 months to minimize potential reverse causation. This exclusion aimed to account for clinicians’ perceptions of cardiovascular risks influencing medication prescription.
The selected 3-month window aligned with the typical psychiatric practice in Sweden. Prescriptions are limited to a maximum of 3 months at a time. Individuals with less than 3 months of follow-up were excluded from the analysis.
What Were The Key Findings?
The study included 278,027 individuals with ADHD aged 6 to 64 years and found that they had a higher incidence of cardiovascular disease (CVD) compared to controls.
The study observed that longer cumulative duration of ADHD medication use was associated with an increased risk of CVD, with methylphenidate being the most commonly used type of medication.
Each 1-year increase in ADHD medication use was associated with a 4% increased risk of CVD, and this risk was higher in children and youth than in adults.
Additionally, the risk of CVD increased with higher average defined daily doses (DDDs) of ADHD medication.
The long-term use of ADHD medication was found to be associated with an increased risk of hypertension and arterial disease.
Lisdexamfetamine and atomoxetine use were also associated with an elevated risk of CVD, with atomoxetine showing a significant association only in the first year of use.
Sensitivity analyses confirmed these findings, and the results remained consistent even when adjusting for propensity scores of ADHD medication use.
However, the study did not find a statistically significant increased risk for arrhythmias, heart failure, ischemic heart disease, thromboembolic disease, or cerebrovascular disease.
The results suggested that increasing cumulative durations of methylphenidate and lisdexamfetamine use were associated with incident CVD, while the associations for atomoxetine were statistically significant only for the first year of use. Furthermore, the association between cumulative duration of ADHD medication use and CVD was similar in females and males. The study emphasized the need for further research to replicate these findings and to explore potential sex-specific differences in cardiovascular responses to ADHD medications.
What Are The Limitations Of This Research?
The study’s strength lies in the prospective recording of data on ADHD medication prescriptions and CVD diagnoses, which reduces the impact of recall bias. However, there are several limitations to consider.
- The identification of patients with CVD was based on recorded diagnoses, potentially leading to under ascertainment of cardiovascular diagnoses.
- Exposure misclassification may have occurred if patients did not adhere to their medication regimen, potentially reducing the observed associations.
- Additionally, while the study accounted for multiple potential confounding variables, causality could not be proven due to the observational nature of the study and the possibility of residual confounding.
- The association observed might have been affected by time-varying confounders, such as other psychotropic medications and lifestyle factors.
- Furthermore, the study did not examine the risk of CVD among individuals with preexisting CVD, which represents a distinct group requiring different study considerations.
- Lastly, the results by type of ADHD medication and type of CVD need replication by studies with larger sample sizes.
Caution for ADHD Medications and Cardiovascular Disease
These results underscore the significance of carefully balancing potential benefits and risks when deciding on long-term ADHD medication use.
Clinicians are advised to be diligent in monitoring patients, especially those on higher doses, and consistently evaluate signs and symptoms of CVD during treatment.
This monitoring is particularly critical given the growing number of individuals using ADHD medication long-term
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