ADHD, Medication, and Height

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CASE VIGNETTE

“Jacob” is a 15-year-old Caucasian male who was diagnosed with attention-deficit/hyperactivity disorder (ADHD) at age 9 years. When started on stimulant medication at age 9 years, he was in the 25th percentile for height and the 10th percentile for weight. Currently at age 15 years, he is in the 17th percentile for height and the 10th percentile for weight. His mother asks whether his stimulant medication has had any impact on his growth. As his psychiatrist, how would you answer her question?

There is mixed evidence for effects of medication treatment for ADHD on growth (height and weight).^1,2 A recent meta-analysis of 18 studies found that long-term methylphenidate treatment might be associated with growth deficit, particularly height, with a small effect size (0.27), although the authors noted the possibility of residual confounding by genetic, prenatal, and/or socioeconomic factors.³

There is also some evidence that ADHD itself many be associated with growth dysregulation, potentially due to effects of the disorder on the neuroendocrine system.^4-7

The Current Study

In order to investigate these associations, Ahlberg and colleagues⁸ used multiple Swedish national registers to compare the height of individuals with ADHD before (treatment-naïve cohort) and after (potentially treated cohort) ADHD medication was introduced in Sweden.

In the potentially treated cohort, they explored the role of prenatal factors, psychiatric and somatic comorbidity, and socioeconomic factors on these associations. They also used a family-based design to explore whether non-affected relatives of individuals with ADHD are at increased risk of shorter height.

Individuals with at least 1 diagnosis of ADHD in the Swedish National Patient Register (NPR; inpatient diagnoses from 1987 and outpatient diagnoses from 2001) were identified using ICD-9 codes. ADHD case individuals had an ADHD diagnosis in the NPR and also participated in Swedish military conscription between 1968 and 2010.

Psychiatric comorbidity was defined as a diagnosis of anxiety, depression, or substance use disorder. Somatic comorbidity was defined as a diagnosis of fetal alcohol syndrome, inflammatory bowel disease, celiac disease, or hypothyroidism.

The Swedish Prescribed Drug Register was used to obtain data on dispensed medications, including amphetamine, methylphenidate, lisdexamfetamine, and atomoxetine. The Swedish Medical Birth Register was used to obtain information on birth weight. The Integrated Database for Labour Market Research provided data on parental education as an indicator of socioeconomic status. The Swedish Military Service Conscription Register contains data on height at approximately age 18 years.

The treatment-naïve cohort consisted of individuals conscripted between 1968 and 1991, and the potentially treated cohort from 1992 to 2010. Using the Swedish Total Population Register, up to 5 conscripted controls for each ADHD case were identified and matched on sex, birth year, and county. Lastly, the Multi-Generation Register was used to identify male full siblings, half siblings, and cousins of individuals with ADHD and controls with available height data from the conscript register.

The authors first compared mean height between ADHD (total and stratified cohorts) and control groups. Height was categorized into 5 groups (below -2, -2 to -1, -1 to 1, 1 to 2, and above 2 standard deviations) and analyzed using conditional logistic regression, adjusting for prenatal factors, medical comorbidity, psychiatric comorbidity, and socioeconomic status. Conditional logistic regression was also used to estimate the odds of shorter or taller height in relatives of individuals with ADHD compared to control relatives.

The study sample included 14,268 individuals with ADHD and 71,339 controls. The mean height of the treatment-naïve cohort was 178.12 cm and 179.27 cm in controls. The mean height of the potentially treated cohort was 178.89 cm and 179.64 cm in controls. In the treatment-naïve cohort (unadjusted model), there was a significant increased odds of far below average height (150-165 cm; OR=1.55) and below average height (166-172 cm; OR=1.31).

The pattern of findings was similar in the potentially treated cohort. In the potentially treated cohort, the adjusted models showed that prenatal factors, psychiatric comorbidity, and socioeconomic status attenuated the relationship between ADHD and shorter height, although the association remained significant.

The family-based analyses included 833,172 relatives. Unaffected full siblings of individuals with ADHD had a significant increased odds of far below average height (150-165 cm; OR=1.18) and below average height (166-172 cm; OR=1.14) compared to full siblings of controls. A similar pattern and magnitude of association was found for maternal and paternal half siblings as well as full cousins.

Study Conclusions

The authors concluded that there was the largest epidemiological study of the association between ADHD and height. Findings suggested that ADHD is associated with shorter height in both treatment-naïve and potentially treated individuals. These associations were attenuated by prenatal factors, psychiatric disorders, and socioeconomic status. Furthermore, relatives of individuals with ADHD were also shorter on average than relatives of controls without ADHD.

Study strengths include the large cumulative sample size, use of national registries, and consideration of important potential confounding factors. Study limitations include an entirely male study sample, potential residual confounding by other social factors, and lack of more detailed information on ADHD medication.

The Bottom Line

The association between ADHD and shorter height at age 18 years is in part explained by confounding, including a shared familial liability for ADHD, prenatal factors, psychiatric comorbidity, and socioeconomic status.

Dr Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric Times®. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

References

1. Cortese S, Holtmann M, Banaschewski T, et al. Practitioner review: current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents. J Child Psychol Psychiatry. 2013;54(3):227-246.

2. Faraone SV, Biederman J, Morley CP, Spencer TJ. Effect of stimulants on height and weight: a review of the literature. J Am Acad Child Adolesc Psychiatry. 2008;47(9):994-1009.

3. Carucci S, Balia C, Gagliano A, et al. Long term methylphenidate exposure and growth in children and adolescents with ADHD. a systematic review and meta-analysis. Neurosci Biobehav Rev. 2021;120:509-525.

4. Faraone SV, Lecendreux M, Konofal E. Growth dysregulation and ADHD: an epidemiologic study of children in France. J Atten Disord. 2012;16(7):572-578.

5. Hanć T, Cieślik J. Growth in stimulant-naive children with attention-deficit/hyperactivity disorder using cross-sectional and longitudinal approaches. Pediatrics. 2008;121(4):e967-e974.

6. Greenhill LL, Swanson JM, Hechtman L, et al. Trajectories of growth associated with long-term stimulant medication in the multimodal treatment study of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2020;59(8):978-989.

7. Ptacek R, Kuzelova H, Paclt I, et al. ADHD and growth: anthropometric changes in medicated and non-medicated ADHD boys. Med Sci Monit. 2009;15(12):CR595-CR599.

8. Ahlberg R, Garcia-Argibay M, Rietz ED, et al. Associations between attention-deficit/hyperactivity disorder (ADHD), ADHD medication, and shorter height: a quasi-experimental and family-based study [published online ahead of print, 2023 Apr 19]. J Am Acad Child Adolesc Psychiatry. 2023;S0890-8567(23)00185-5.