ADHD, medications and height

VIGNETTE CASE

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

There is conflicting evidence of the effects of ADHD drug treatment on growth (height and weight).^1.2 A recent meta-analysis of 18 studies found that long-term treatment with methylphenidate could be associated with growth failure, particularly in height, with a small effect size (0.27), although the authors noted the possibility of residual confusion from genetic, prenatal and/or socioeconomic factors.³

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

The current study

To investigate these associations, Ahlberg and colleagues⁸ used multiple Swedish national registries to compare the height of individuals with ADHD before (treatment-vessel cohort) and after (potentially treated cohort) ADHD medications were 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 unaffected relatives of individuals with ADHD are at increased risk for shorter stature.

Individuals with at least 1 ADHD diagnosis in the Swedish National Patient Registry (NPR; inpatient diagnoses since 1987 and outpatient diagnoses since 2001) were identified using ICD-9 codes. The ADHD cases had a diagnosis of ADHD 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 it was defined as a diagnosis of fetal alcohol syndrome, inflammatory bowel disease, celiac disease, or hypothyroidism.

The Swedish Register of Prescribed Medicines was used to obtain data on dispensed medicines, including amphetamine, methylphenidate, lisdexamfetamine and atomoxetine. The Swedish birth registry was used to obtain information on birth weight. The Integrated Labor Market Research Database provided data on parental education as an indicator of socioeconomic status. The Swedish military service draft register contains data on height at the age of approximately 18 years.

The aisle treated cohort was composed of individuals enrolled between 1968 and 1991 and the potentially treated cohort from 1992 to 2010. Using the Swedish Total Population Registry, up to 5 enrolled controls were identified for each ADHD case and compared for gender, year of birth, and county. Finally, the multigenerational registry was used to identify siblings, half-siblings, and cousins ​​of individuals with ADHD and controls with height data available from the draft registry.

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

The study sample included 14,268 individuals with ADHD and 71,339 controls. The mean height of the treatment-aisle 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 the controls. In the center aisle cohort (unadjusted model), there was a significant increase in the odds of much shorter than mean height (150-165 cm; OR=1.55) and lower than mean height (166-172 cm; OR =1.31).

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

Household-based analyzes included 833,172 relatives. Unaffected full siblings of individuals with ADHD had significantly increased odds of much shorter than mean height (150-165 cm; OR=1.18) and shorter than mean height (166-172 cm; OR=1.14 ) than its full siblings of controls. A similar pattern and extent of association was found for maternal and paternal half-siblings and full cousins.

Study conclusions

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

Strengths of the study include the large cumulative sample size, use of national registries, and consideration of important potential confounders. Study limitations include an all-male study sample, potential residual confounding from other social factors, and lack of more detailed information about ADHD medications.

The bottom line

The association between ADHD and low height at age 18 is explained in part by confounds, including a shared family responsibility for ADHD, prenatal factors, psychiatric comorbidities, and socioeconomic status.

Dr. Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Augusta, Georgia. He sits on the editorial board and serves as section head for schizophrenia 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 ADHD medication treatment 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 literature review.J Am Acad Child Adolescent Psychiatry. 2008;47(9):994-1009.

3. Carucci S, Balia C, Gagliano A, et al. Long-term exposure and growth to methylphenidate 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 epidemiological study of children in France.J Atten Disorder. 2012;16(7):572-578.

5. Han T, Cielik 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. Growth trajectories associated with long-term stimulant medications in the attention-deficit/hyperactivity disorder multimodal treatment study.J Am Acad Child Adolescent Psychiatry. 2020;59(8):978-989.

7. Ptacek R, Kuzelova H, Paclt I, et al. ADHD and growth: anthropometric changes in medicated and unmedicated 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 medications, and shorter stature: A quasi-experimental, family-based study [published online ahead of print, 2023 Apr 19].J Am Acad Child Adolescent Psychiatry. 2023;S0890-8567(23)00185-5.