Raine ADHD Study: Long-term outcomes associated with stimulant medication in the treatment of ADHD in children (PDF 1.05MB)

The short term-benefits of methylphenidate and dexamphetamine in the management of Attention Deficit Hyperactivity Disorder (ADHD) symptoms are well described throughout the literature. Similarly, the short-term side-effects of these stimulant medications are well-documented. However, the long-term benefits and side-effects have been less well studied.

This project uses longitudinal data collected as part of the Western Australian Pregnancy Birth Cohort to examine the long-term social, emotional, school-based, growth, and cardiovascular outcomes associated with the use of stimulant medication in the treatment of ADHD. These outcomes are measured at the age of 14-years.

ADHD Diagnosis and Outcomes

Children with a diagnosis of ADHD as reported by parents (regardless of medication use), perform significantly worse at age 14 years on measures of depression, self perception, social functioning, academic performance, school enjoyment and attention than those without a diagnosis.

This is consistent with previous research and suggests that children diagnosed with ADHD have an underlying condition that impacts negatively on a range of long-term life skills.

　Outcomes Associated with Medication-Use for Children Diagnosed with ADHD

Social/Emotional and School-Based outcomes

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No significant differences based on medication-use were noted for the following measures taken at 14 years of age: depression, self-perception, and social-functioning.

• Whilst no statistically significant results were noted, a trend toward slightly higher depression scores was noted with the use of medication.

• A trend toward slightly lower self-esteem and social functioning was also noted with medication use at one time point or two time points. However, consistent medication-use at all time points, including at 14 years, trended toward slightly improved self-perception and social functioning.

• It should be emphasised that where these trends were noted, the effect sizes were small and were not statistically significant

　School-Based outcomes

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In children with ADHD, ever receiving stimulant medication was found to increase the odds of being identified as performing below age-level by a classroom teacher by a factor of 10.5 times (compared to never receiving stimulant medication).

• Absenteeism and school enjoyment were not found to be significantly predicted by stimulant medication-use.

• It should be noted that analyses examining academic performance and absenteeism were limited due to low sample size and the lack of ability to examine differences based on the level of exposure to medication.

　Height and Weight

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Height: There was no significant difference in average height or weight (at 14 years of age) when comparing children who were consistently on medication to those who were never on medication.

• Non-significant trends indicated very little difference in growth measures between the ‘consistently medicated’ and ‘never medicated’ groups.

• This is inconsistent with previous research; however it is likely that the small sample sizes in the stimulant exposure categories may have prevented significant results from being identified.

Cardiovascular Function

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Systolic Blood Pressure: no significant difference based on stimulant medication use was noted.

• Diastolic Blood Pressure: children who had consistently received stimulant medication at all time points had significantly greater diastolic blood pressure than children who had never received medication (10.79 mmHg higher).

• Children who had consistently received stimulant medication at all time points (including when cardiovascular health was measured) also had a significantly greater diastolic blood pressure than children who were currently receiving medication but had not in the past (7.05 mmHg higher).

o These findings suggest that an elevation in diastolic blood pressure may not be due solely to the immediate short-term effects of stimulant medication on cardiovascular function.

• Resting Heart Rate: no significant difference based on stimulant medication use was noted. However a non-significant trend of higher resting heart rate in children receiving stimulant medication at all time points in the study was noted.

Change in Key ADHD Symptoms

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On average, externalising behaviour and attentional problems did not appear to improve or worsen significantly between the ages of 5 and 14 in children with ADHD, regardless of medication use.

• Where an effect was noted, this was in the direction of symptoms worsening with the use of ADHD medication (however, this effect was small and not statistically significant).

• The results seem to indicate that there is little long-term benefit of stimulant medication in the core symptoms of ADHD. This is not unexpected, as medication is used for the temporary management of core ADHD symptoms rather than as a cure.

• Some concern may be raised over the apparent lack of effect with regard to children ‘currently’ on medication, as it would be expected that some short-term reduction in symptoms would be observed. However, the lack of a short-term effect may be explained by the fact that

parents

completed the assessments of core symptoms. Given that medication is taken mostly during school hours, the ‘onboard’ effects of medication may not be apparent to parents.

The strength of the current study lies in its ability to provide a unique long-term view of a wide range of outcomes and their associations with the use of stimulant medication in the treatment of ADHD. Whilst limitations of the study prevent any strong causal relationships from being identified, some interesting results were observed that indicate rigorous research into the area is strongly warranted.

• The lack of significant improvements in long-term social, emotional and academic functioning associated with the use of stimulant medication suggests a purpose-designed, longitudinal research study should be conducted to better understand the suspected long-term social, emotional and educational benefits of stimulant medication in the treatment of ADHD.

• The results also indicated that between the age of 8 and 14 years there may be an effect of stimulant medication on diastolic blood pressure above and beyond the well-established immediate short-term effects on cardiovascular function. The finding that consistent use of medication was associated with an average elevation 10mmHg at 14-years of age indicates that the long-term cardiovascular implications of stimulant medication-use need to take a high priority when determining directions for future research.

There are a number of limitations associated with the current study that should be taken into account when interpreting the results:

• The relatively low sample size in the stimulant-use comparison groups may have reduced the chance of finding real differences where they may have existed.

• Whilst a number of steps were taken to reduce the possible biases between the comparison groups, particularly with regard to symptom severity, it is still possible that these may not be adequately controlled for, threatening the validity of some multivariable models.

• Measures used to document ADHD symptoms (CBCL 1991) may have been inadequate to document severity (though previous research has documented it to be useful in differentiating ADHD from non-ADHD cases). The version of the Achenbach scales used does not document ICD10/DSM IV criteria.

• Due to sample size issues, dextroamphetamine and methylphenidate use were combined into one composite group: ‘stimulant use’. This prevented the effects of the different medications on the various outcomes to be identified.

• Dosage and adherence to medication was not measured as part of the study. Medication usage at each of the time points was determined by the mother reporting that the medication had been used in the 6 months prior to completing the questionnaire.

• ADHD diagnosis by a medical professional was reported by the child’s parent and was not validated using diagnostic tools.

• The subtypes of ADHD were not able to be analysed separately (due to sample size).

full study http://www.health.wa.gov.au/publications/documents/MICADHD_Raine_ADHD_Study_report_022010.pdf