Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with estimates of global prevalence rates ranging from 5% (Polanczyk et al. Reference Polanczyk, de Lima, Horta, Biederman and Rohde2007) to 8% (Ayano et al. Reference Ayano, Demelash, Gizachew, Tsegay and Alati2023). Clinical practice guidelines (CPGs) in the UK (NICE 2018), Europe (Taylor et al. Reference Taylor, Döpfner, Sergeant, Asherson, Banaschewski, Buitelaar, Coghill, Danckaerts, Rothenberger, Sonuga-Barke, Steinhausen and Zuddas2004), and America (Wolraich et al. Reference Wolraich, Hagan, Allan, Chan, Davison, Earls, Evans, Flinn, Froehlich and Frost2019) recommend stimulant medications as first line pharmacological treatment for ADHD in children over the age of 5, alongside behavioural and educational interventions. Methylphenidate (MPH) is the most common stimulant used in Europe (Taylor et al. Reference Taylor, Döpfner, Sergeant, Asherson, Banaschewski, Buitelaar, Coghill, Danckaerts, Rothenberger, Sonuga-Barke, Steinhausen and Zuddas2004) and has a strong evidence base with large effect sizes (0.77−.91) in reducing core ADHD symptoms (Faraone & Buitelaar, Reference Faraone and Buitelaar2010; Cortese et al. Reference Cortese, Adamo, Del Giovane, Mohr-Jensen, Hayes, Carucci, Atkinson, Tessari, Banaschewski, Coghill, Hollis, Simonoff, Zuddas, Barbui, Purgato, Steinhausen, Shokraneh, Xia and Cipriani2018). Most adverse effects of MPH are considered non-serious (Storebø et al. Reference Storebø, Storm, Pereira Ribeiro, Skoog, Groth, Callesen, Schaug, Darling Rasmussen, Huus, Zwi, Kirubakaran, Simonsen and Gluud2023), however there remains some controversy over the effects of MPH on growth and cardiovascular parameters. Many studies show MPH is associated with weight suppression (Faraone et al. Reference Faraone, Biederman, Morley and Spencer2008; Poulton et al. Reference Poulton, Melzer, Tait, Garnett, Cowell, Baur and Clarke2013; Schwartz et al. Reference Schwartz, Bailey-Davis, Bandeen-Roche, Pollak, Hirsch, Nau, Liu and Glass2014; Powell et al. Reference Powell, Frydenberg and Thomsen2015; Lentferink et al. Reference Lentferink, van de Garde, Knibbe and van der Vorst2018; Ross et al. Reference Ross, Sapre, Stanislaus and Poulton2020; Waxmonsky et al. Reference Waxmonsky, Pelham, Campa, Waschbusch, Li, Marshall, Babocsai, Humphery, Gnagy, Swanson, Hanć, Fallahazad and Pelham2020; Wang et al. Reference Wang, Huang, Chou and Lee2022; Carucci et al. Reference Carucci, Zuddas, Lampis, Man, Balia, Buitelaar, Danckaerts, Dittmann, Donno, Falissard, Gagliano, Garas, Häge, Hollis, Inglis, Konrad, Kovshoff, Liddle, McCarthy, Neubert, Nagy, Rosenthal, Sonuga-Barke, Wong, Banaschewski and Coghill2024). However, several longer term studies (over 10 – 16 years) have not shown this effect (Biederman et al. Reference Biederman, Spencer, Monuteaux and Faraone2010; Greenhill et al. Reference Greenhill, Swanson, Hechtman, Waxmonsky, Arnold, Molina, Hinshaw, Jensen, Abikoff, Wigal, Stehli, Howard, Hermanussen and Hanć2020), and other studies have reported that while stimulant use has been associated with initial periods of weight loss, this is then followed by rebound weight gain, ultimately leading to stimulant-treated adolescents and young adults weighing more than control groups (Schwartz et al. Reference Schwartz, Bailey-Davis, Bandeen-Roche, Pollak, Hirsch, Nau, Liu and Glass2014; Swanson et al. Reference Swanson, Arnold, Molina, Sibley, Hechtman, Hinshaw, Abikoff, Stehli, Owens, Mitchell, Nichols, Howard, Greenhill, Hoza, Newcorn, Jensen, Vitiello, Wigal, Epstein, Tamm, Lakes, Waxmonsky, Lerner, Etcovitch, Murray, Muenke, Acosta, Arcos‐Burgos, Pelham and Kraemer2017; Greenhill et al. Reference Greenhill, Swanson, Hechtman, Waxmonsky, Arnold, Molina, Hinshaw, Jensen, Abikoff, Wigal, Stehli, Howard, Hermanussen and Hanć2020). Overall, the evidence suggests that MPH is associated with weight loss, at least in the short to medium term, and a recent Cochrane review calculated the relative risk of weight loss for MPH use in children and adolescents is 5.4, compared to control groups (Storebø et al. Reference Storebø, Storm, Pereira Ribeiro, Skoog, Groth, Callesen, Schaug, Darling Rasmussen, Huus, Zwi, Kirubakaran, Simonsen and Gluud2023).
With regard to height, some studies have reported an association between MPH and height suppression (Charach et al. Reference Charach, Figueroa, Chen, Ickowicz and Schachar2006; Poulton et al. Reference Poulton, Melzer, Tait, Garnett, Cowell, Baur and Clarke2013; Powell et al. Reference Powell, Frydenberg and Thomsen2015; Díez-Suárez et al. Reference Díez-Suárez, Vallejo-Valdivielso, Marín-Méndez, de Castro-Manglano and outullo2017; Lentferink et al. Reference Lentferink, van de Garde, Knibbe and van der Vorst2018; Greenhill et al. Reference Greenhill, Swanson, Hechtman, Waxmonsky, Arnold, Molina, Hinshaw, Jensen, Abikoff, Wigal, Stehli, Howard, Hermanussen and Hanć2020; Waxmonsky et al. Reference Waxmonsky, Pelham, Campa, Waschbusch, Li, Marshall, Babocsai, Humphery, Gnagy, Swanson, Hanć, Fallahazad and Pelham2020), while others have not (Biederman et al. Reference Biederman, Spencer, Monuteaux and Faraone2010; Carucci et al. Reference Carucci, Zuddas, Lampis, Man, Balia, Buitelaar, Danckaerts, Dittmann, Donno, Falissard, Gagliano, Garas, Häge, Hollis, Inglis, Konrad, Kovshoff, Liddle, McCarthy, Neubert, Nagy, Rosenthal, Sonuga-Barke, Wong, Banaschewski and Coghill2024; Harstad et al. Reference Harstad, Weaver, Katusic, Colligan, Kumar, Chan, Voigt and Barbaresi2014; Man et al. Reference Man, Häge, Banaschewski, Inglis, Buitelaar, Carucci, Danckaerts, Dittmann, Falissard, Garas, Hollis, Konrad, Kovshoff, Liddle, McCarthy, Neubert, Nagy, Rosenthal, Sonuga-Barke, Zuddas, Wong, Coghill, Couper, Masi, Gagliano, Lamberti, Maschietto, Costantino, Morosini, Fazzi, Oehler, Pitzer, Fegert, Häßler, Renner, Härtling, Romanos, Alfred, Roessner, Wallitza and Uebel-von Sandersleben2023). A meta-analysis including over 4000 children and adolescents with ADHD reported significant reductions in height after 24 months of MPH treatment, albeit the effect size was small (.27) (Carucci et al. Reference Carucci, Balia, Gagliano, Lampis, Buitelaar, Danckaerts, Dittmann, Garas, Hollis, Inglis, Konrad, Kovshoff, Liddle, McCarthy, Nagy, Panei, Romaniello, Usala, Wong, Banaschewski, Sonuga-Barke, Coghill and Zuddas2021). Clinical moderators associated with larger reductions in weight and height include higher doses of MPH (Charach et al. Reference Charach, Figueroa, Chen, Ickowicz and Schachar2006; Powell et al. Reference Powell, Frydenberg and Thomsen2015; Díez-Suárez et al. Reference Díez-Suárez, Vallejo-Valdivielso, Marín-Méndez, de Castro-Manglano and outullo2017; Ross et al. Reference Ross, Sapre, Stanislaus and Poulton2020), increased lifetime exposure to CNS stimulants (Swanson et al. Reference Swanson, Arnold, Molina, Sibley, Hechtman, Hinshaw, Abikoff, Stehli, Owens, Mitchell, Nichols, Howard, Greenhill, Hoza, Newcorn, Jensen, Vitiello, Wigal, Epstein, Tamm, Lakes, Waxmonsky, Lerner, Etcovitch, Murray, Muenke, Acosta, Arcos‐Burgos, Pelham and Kraemer2017; Schwartz et al. Reference Schwartz, Bailey-Davis, Bandeen-Roche, Pollak, Hirsch, Nau, Liu and Glass2014), higher baseline weight or height (Faraone et al. Reference Faraone, Biederman, Morley and Spencer2008; Landgren et al. Reference Landgren, Nasic, Johnson, Lövoll, Holmgren and Fernell2017) and female gender (Lisska & Rivkees, Reference Lisska and Rivkees2003; Lentferink et al. Reference Lentferink, van de Garde, Knibbe and van der Vorst2018).
In relation to blood pressure, the majority of studies report MPH is associated with increased Systolic Blood Pressure (SBP) (Hennissen et al. Reference Hennissen, Bakker, Banaschewski, Carucci, Coghill, Danckaerts, Dittmann, Hollis, Kovshoff, McCarthy, Nagy, Sonuga-Barke, Wong, Zuddas, Rosenthal and Buitelaar2017; Buitelaar et al. Reference Buitelaar, van de Loo-Neus, Hennissen, Greven, Hoekstra, Nagy, Ramos-Quiroga, Rosenthal, Kabir, Man, IC, Coghill, Häge, Banaschewski, Inglis, Carucci, Danckaerts, Dittmann, Falissard, Garas, Hollis, Konrad, Kovshoff, Liddle, McCarthy, Neubert, Sonuga-Barke and Zuddas2022), Diastolic Blood Pressure (DBP) (Cortese et al. Reference Cortese, Adamo, Del Giovane, Mohr-Jensen, Hayes, Carucci, Atkinson, Tessari, Banaschewski, Coghill, Hollis, Simonoff, Zuddas, Barbui, Purgato, Steinhausen, Shokraneh, Xia and Cipriani2018; Storebø et al. Reference Storebø, Storm, Pereira Ribeiro, Skoog, Groth, Callesen, Schaug, Darling Rasmussen, Huus, Zwi, Kirubakaran, Simonsen and Gluud2023) or both SBP and DBP (St. Amour et al. Reference St. Amour, O’Leary, Cairney and Wade2018; Man et al. Reference Man, Häge, Banaschewski, Inglis, Buitelaar, Carucci, Danckaerts, Dittmann, Falissard, Garas, Hollis, Konrad, Kovshoff, Liddle, McCarthy, Neubert, Nagy, Rosenthal, Sonuga-Barke, Zuddas, Wong, Coghill, Couper, Masi, Gagliano, Lamberti, Maschietto, Costantino, Morosini, Fazzi, Oehler, Pitzer, Fegert, Häßler, Renner, Härtling, Romanos, Alfred, Roessner, Wallitza and Uebel-von Sandersleben2023; Farhat et al. Reference Farhat, Lannes, Del Giovane, Parlatini, Garcia-Argibay, Ostinelli, Tomlinson, Chang, Larsson, Fava, Montastruc, Cipriani, Revet and Cortese2025). The study by Man et al is a large 2-year prospective naturalistic study across 27 centres in Europe, known as the ADDUCE project (Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects), which was funded by the European Union to investigate the long-term ( >52 weeks) effects of MPH in children and adolescents. This project found mean SBP increased between baseline and 24 months from 108 to 113 mmHg (P < .0001) and mean DBP increased from 65 to 67 mmHg (p = .02) (Man et al. Reference Man, Häge, Banaschewski, Inglis, Buitelaar, Carucci, Danckaerts, Dittmann, Falissard, Garas, Hollis, Konrad, Kovshoff, Liddle, McCarthy, Neubert, Nagy, Rosenthal, Sonuga-Barke, Zuddas, Wong, Coghill, Couper, Masi, Gagliano, Lamberti, Maschietto, Costantino, Morosini, Fazzi, Oehler, Pitzer, Fegert, Häßler, Renner, Härtling, Romanos, Alfred, Roessner, Wallitza and Uebel-von Sandersleben2023).
Two other studies however have reported opposing findings: one cross-sectional study reported no effect of stimulants on blood pressure compared to population norms (Suess et al. Reference Suess, Chrenka, Kharbanda, Asche, O’Connor, Ekstrom and Benziger2024) and one retrospective uncontrolled study reported that long-term stimulant use was associated with a reduction in BP centiles (Conzelmann et al. Reference Conzelmann, Müller, Jans, Trott, Keil, Gerlach and Renner2019).
Studies in relation to heart rate (HR) appear to be more consistent; the majority report that MPH is associated with increased HR (St. Amour et al. Reference St. Amour, O’Leary, Cairney and Wade2018; Buitelaar et al. Reference Buitelaar, van de Loo-Neus, Hennissen, Greven, Hoekstra, Nagy, Ramos-Quiroga, Rosenthal, Kabir, Man, IC, Coghill, Häge, Banaschewski, Inglis, Carucci, Danckaerts, Dittmann, Falissard, Garas, Hollis, Konrad, Kovshoff, Liddle, McCarthy, Neubert, Sonuga-Barke and Zuddas2022; Man et al. Reference Man, Häge, Banaschewski, Inglis, Buitelaar, Carucci, Danckaerts, Dittmann, Falissard, Garas, Hollis, Konrad, Kovshoff, Liddle, McCarthy, Neubert, Nagy, Rosenthal, Sonuga-Barke, Zuddas, Wong, Coghill, Couper, Masi, Gagliano, Lamberti, Maschietto, Costantino, Morosini, Fazzi, Oehler, Pitzer, Fegert, Häßler, Renner, Härtling, Romanos, Alfred, Roessner, Wallitza and Uebel-von Sandersleben2023; Storebø et al. Reference Storebø, Storm, Pereira Ribeiro, Skoog, Groth, Callesen, Schaug, Darling Rasmussen, Huus, Zwi, Kirubakaran, Simonsen and Gluud2023). Most studies report changes in absolute BP and HR (mmHg or bpm), but few report percentiles for age and gender (Vitiello et al. Reference Vitiello, Elliott, Swanson, Arnold, Hechtman, Abikoff, Molina, Wells, Wigal, Jensen, Greenhill, Kaltman, Severe, Odbert, Hur and Gibbons2012; Suess et al. Reference Suess, Chrenka, Kharbanda, Asche, O’Connor, Ekstrom and Benziger2024).
In children and adolescents, BP typically increases with age, while HR decreases. Conversion of both blood pressure and HR to percentiles is recommended by the European ADHD Guideline Group (EAGG) (Graham et al. Reference Graham, Banaschewski, Buitelaar, Coghill, Danckaerts, Dittmann, Döpfner, Hamilton, Hollis and Holtmann2011) to accurately detect elevated BP (defined as SBP or DBP values ≥ 90th percentile for age, gender, and height), hypertension (BP > 95th percentile for age, gender, and height) and tachycardia (defined as HR > 95th percentile for age and gender (Vitiello et al. Reference Vitiello, Elliott, Swanson, Arnold, Hechtman, Abikoff, Molina, Wells, Wigal, Jensen, Greenhill, Kaltman, Severe, Odbert, Hur and Gibbons2012). Similarly, NICE guidelines recommend that weight and height be plotted against local norms so that stimulant-associated growth deceleration can be detected (NICE 2018).
The lack of clarity on the effects of MPH on growth and BP leads to risk of overestimation or underestimation of these adverse effects (Cortese et al. Reference Cortese, Holtmann, Banaschewski, Buitelaar, Coghill, Danckaerts, Dittmann, Graham, Taylor and Sergeant2013). In Ireland, a 2022 report raised concerns about inadequate physical monitoring practices in an Irish Child and Adolescent Mental Health Service (CAMHS) (Maskey, Reference Maskey2022), and Irish parents are worried about the adverse effects of ADHD medication (Flood et al. Reference Flood, Hayden, Gavin and McNicholas2019). The prescription of stimulant medications for children with ADHD in Ireland is rising (Mac Avin et al. Reference Mac Avin, Teeling and Bennett2020) and it is important to understand and quantify the associated growth and cardiovascular adverse effects of MPH.
ADMiRE is a specialist ADHD clinic located in south-west Dublin, Ireland. The ADMiRE clinical pathway, adapted from the Dundee Clinical Care Pathway (Coghill & Seth, Reference Coghill and Seth2015), provides an evidence-based structured protocol for assessment and management of ADHD in children and adolescents (McGrath, Reference McGrath2024). The ADMiRE management protocol adheres closely to NICE guidelines for physical health monitoring for children on ADHD medication (Dalrymple et al. Reference Dalrymple, Maxwell, Russell and Duthie2020) and there is a comprehensive physical health dataset for all children attending the service.
The aims of this retrospective observational study were 1) to investigate whether children on MPH who were attending ADMiRE showed a change in weight, height, BP, or HR percentiles when compared with their pre-MPH measures, and 2) to determine if there was an association between percentile changes in these measures and clinical moderators such as MPH dose and length of time on MPH. Based on the literature it was hypothesised that MPH use would be associated with a reduction in weight and height percentiles and an increase in BP and HR percentiles, and these changes would be associated with higher MPH doses and number of years prescribed MPH. To our knowledge this is the first study to investigate the physical health effects of MPH on children in Ireland.
Methods
Patients and setting
This is a retrospective observational cohort study of young people attending ADMiRE, a specialist ADHD service that accepts referrals of young people age 6 – 17 from three community CAMHS teams in South-west Dublin, when a diagnosis of ADHD is suspected. Data were included from all patients attending ADMiRE who had a confirmed diagnosis of ADHD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) for which they were prescribed MPH. Data for patients who did not have a formal diagnosis of ADHD, were not prescribed MPH, were prescribed additional psychotropic medications (excluding melatonin), or who reported non-adherence to MPH were excluded from the analysis. In ADMiRE, physical health data is measured by psychiatric nurses and doctors. BP is typically measured using an electronic BP machine, weight is recorded on an electronic scale, and height is measured using a stadiometer. All equipment undergoes regular checks and routine calibration.
Data collection
Clinical records were retrospectively reviewed and data on height (cm), weight (kg), BP (mmHg) and HR (beats per minute, bpm) were recorded from the baseline clinic visit before commencement of MPH (T1), and again from the patient’s most recent clinic review (T2). Percentiles for height, weight, BP and HR at baseline (T1) and at follow-up (T2) were calculated in Microsoft Excel® using the lambda-mu-sigma (LMS) method (Cole & Green, Reference Cole and Green1992). The LMS method is used extensively in the derivation of centile data and controls for the skewness of population datasets, which allows data to be assessed as if it were Gaussian in distribution. Height and weight percentiles were calculated based on normal population data derived from the UK90 study (Freeman et al. Reference Freeman, Cole, Chinn, Jones, White and Preece1995) used by the Royal College of Paediatrics and Child Health in the UK. Blood pressure centiles were calculated from the normative distribution data of BP in healthy children from the Fourth Report (National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents 2004) used in the American Academy of Paediatrics Clinical Practice Guidelines for screening and management of high blood pressure in children (Flynn et al. Reference Flynn, Kaelber, Baker-Smith, Blowey, Carroll, Daniels, de Ferranti, Dionne, Falkner and Flinn2017). HR centiles were calculated from normative data derived from a systematic review including over 143,000 patients (Fleming et al. Reference Fleming, Thompson, Stevens, Heneghan, Plüddemann, Maconochie, Tarassenko and Mant2011).
Statistics
Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 26.0 (SPSS Inc., IBM, New York, USA). Descriptive analyses on demographic and clinical data were performed for both categorical and continuous variables, as appropriate. Data were examined to determine if normally distributed by visual inspection using histograms and Q-Q plots. Alpha level for statistical significance was 0.05. Paired student t-tests were used to examine for changes in growth and cardiovascular measurements from T1 (baseline) to T2. Multiple regression analyses were conducted to evaluate for any association between growth or cardiovascular centile changes and independent variables of MPH dose relative to patient weight (mg/kg), time on stimulant medication (years), gender, and baseline weight and height centiles.
Results
Baseline characteristics
143 young people with a diagnosis of ADHD were attending ADMIRE and prescribed MPH at the time of data collection. Four reported non-adherence to MPH. Sixteen did not have baseline height or weight data available and the growth analysis was completed on the remaining 123 participants. Table 1 demonstrates the baseline clinical characteristics of the participants. 99 (80.5%) were male and mean age at commencement of MPH was 10.8 yrs ( ± 2.8, range 5 to 17.5 years). Time on stimulant medication (T2-T1) varied for each patient with a range of 2 weeks to 10.4 years and the mean treatment period was 2.5 years ± 2.1 years. MPH mean dose was 31.9 ± 13.7 mg and relative to patient weight was 0.67 ± 0.32 mg/kg. Mean daily dose was significantly higher for females (37.5 ± 12.4 mg, n = 24) compared to males (30.5 ± 13.7, n = 99, p = .025), however there was no significant difference in dose relative to weight (mg/kg) between males (0.65 ± 0.31, n = 99) and females (0.75 ± 0.37, n = 24, p = .182).
Clinical variables of total cohort
Cardiovascular data were incomplete for 25 patients (BP) and 31 patients (HR). Blood pressure analysis included data from 118 participants (78% were male, age 10.8 ± 2.7 yrs, MPH dose 0.66 ± 0.33 mg/Kg) and HR analysis included data from 112 participants (79% were male, age 10.8 ± 2.7 yrs, mean dose 0.67 ± 0.34 mg/Kg).
Weight and BMI
Pre-treatment mean weight centile was 64.7 ± 30.3 and pre-treatment BMI centile was 65.0 ± 28.4 indicating that this population were slightly heavier than expected for their age (see Table 2). At follow-up (T2) mean weight centile reduced by 5.01 ± 15.6 percentile points to 59.7 ± 32.8 (t(122) = −3.52, p = .001). BMI centile significantly reduced by 4.56 ±19.8 percentile points to 60.5 ± 33.2 (t(122) = −2.52, p = .013).
Changes in physical health parameters from pre-treatment (T1) to most recent clinic visit (T2)
Multiple regression analysis results are shown in table 3. Weight centile change was negatively correlated with MPH dose (mg/kg) (β = −0.56, t(122) = −7.11, P < .0001), indicating that the higher MPH doses were associated with a greater reduction in weight centiles. Gender and baseline weight were not associated with weight centile change. The number of years on MPH was positively correlated with changes in weight centiles (β = 0.217, t(122) = 2.85, p = .005), suggesting that longer duration of MPH use was associated with recovery in weight gain.
Results of multiple regression analysis for clinical variables associated with weight and height centile reduction
* Depicts significance after Bonferroni correction for multiple comparisons.
Height
Mean height centiles at baseline were 57.6 ± 31.1 and at follow-up (T2) were 54.2 ± 30.8. This represents a significant reduction of 3.4 ± 13.9 percentile points (t(120) = −2.7, p = .007). There was no significant difference in height centile reduction between males and females (p = .09). No correlation was found between height centile change and number of years on MPH (p = .41), gender (p = .08) or stimulant dose (mg/kg) (p = .63), see table 3. There was a negative correlation between baseline height and height centile change (β = −0.24, t(120) = −2.7, p = .008), suggesting those who were taller for their age at baseline experienced more height suppression.
Blood pressure
Baseline SBP centiles were slightly less than expected for age and gender (46.9 ± 30.2) while baseline DBP centiles were slightly higher than expected for age and gender (61.9 ± 22.2). Over the treatment period, from T1 to T2, there were no significant changes in mean SBP centiles (+1.18 ± 35.2, p = .72) or mean DBP centiles ( −1.87 ± 27.0, p = .46) in this cohort (n = 118). Consistent with increasing age, absolute SBP increased significantly from 103.7 ± 12.2 mmHg at T1 to 108.9 ± 9.9 mmHg at T2 (P < .0001). Absolute DBP did not increase (p = .72).
Heart rate
Absolute HR (bpm) did not significantly increase from T1 (81.9 bpm ±12.5) to T2 (83.9 bpm ± 13.7, p = .19). HR centiles significantly increased by 15 ± 33.7 centile points, p < 0.0001, see table 2. Independent variables including BMI centile, stimulant dose (mg/Kg), and time on stimulant (years) were not associated with change in HR centiles, F (3,112) = 0.83, p = .53. The prevalence of tachycardia (HR > 95th percentile) was 3.4% (n = 4) at both T1 and T2. Only one participant exhibited tachycardia at both T1 and T2.
Discussion
This is a clinically-based retrospective observational study of weight, height, BMI, blood pressure and HR in children and adolescents diagnosed with ADHD and treated with MPH in a specialist ADHD service. Over an average treatment period of 2.5 years there was a significant reduction in mean weight, BMI, and height centiles, and an increase in HR centiles. Weight reduction was associated with higher MPH dose and this effect appeared to attenuate over time. Contrary to our hypothesis, no changes were observed in BP centiles.
Our findings are congruent with a number of studies that reported that weight suppression is associated with higher stimulant doses (MTA Cooperative Group 2004; Faraone et al. Reference Faraone, Biederman, Morley and Spencer2008), and that these effects attenuate over time, with possible resumption of the normal trajectory of weight gain after several years (Poulton, Reference Poulton2005; Swanson et al. Reference Swanson, Elliott, Greenhill, Wigal, Arnold, Vitiello, Hechtman, Epstein, Pelham and Abikoff2007; Faraone et al. Reference Faraone, Biederman, Morley and Spencer2008; McCarthy et al. Reference McCarthy, Neubert, Man, Banaschewski, Buitelaar, Carucci, Coghill, Danckaerts, Falissard, Garas, Häge, Hollis, Inglis, Kovshoff, Liddle, Mechler, Nagy, Rosenthal, Schlack, Sonuga-Barke, Zuddas and Wong2018). The correlation between higher MPH doses and weight loss is particularly relevant to clinicians since some CPGs, such as those from the American Academy of Paediatrics (Wolraich et al. Reference Wolraich, Hagan, Allan, Chan, Davison, Earls, Evans, Flinn, Froehlich and Frost2019), recommend titrating ADHD medication to the maximum tolerated dose. Our results suggest that caution should be exercised in such dose titrations, with careful consideration of the risk of weight centile reduction. The finding that baseline height predicted the magnitude of change in growth has been reported by others (Faraone et al. Reference Faraone, Biederman, Morley and Spencer2008; Landgren et al. Reference Landgren, Nasic, Johnson, Lövoll, Holmgren and Fernell2017) and a recent metanalysis by Carucci et al. (Reference Carucci, Balia, Gagliano, Lampis, Buitelaar, Danckaerts, Dittmann, Garas, Hollis, Inglis, Konrad, Kovshoff, Liddle, McCarthy, Nagy, Panei, Romaniello, Usala, Wong, Banaschewski, Sonuga-Barke, Coghill and Zuddas2021) also found that MPH-associated height suppression was not related to MPH dose.
No significant changes in BP centiles were found over the treatment period. The conversion of absolute BP (mmHg) to percentiles is necessary to account for the natural increase of BP with age and is recommended by CPGs (Flynn et al. Reference Flynn, Kaelber, Baker-Smith, Blowey, Carroll, Daniels, de Ferranti, Dionne, Falkner and Flinn2017). Our finding that absolute SBP increased from T1 to T2 while SBP percentiles remained unchanged, underscores the importance of reporting centiles. Without this adjustment, the analysis would have erroneously suggested an association between MPH and SBP increase. These findings are contrary to those of Landgren et al. (Reference Landgren, Nasic, Johnson, Lövoll, Holmgren and Fernell2017) who reported MPH (0.95mg/Kg) was associated with significant increases in SBP and DBP percentiles from baseline to follow-up at 3 years. Several factors could explain the absence of an increase in BP percentiles observed in our study. Firstly, average dose was 0.66 mg/Kg which is considered low (Cortese et al. Reference Cortese, Holtmann, Banaschewski, Buitelaar, Coghill, Danckaerts, Dittmann, Graham, Taylor and Sergeant2013). Secondly, medication non-compliance is common in young people with ADHD (Ferrin et al. Reference Ferrin, Häge, Swanson, Wong, Dittmann, Banaschewski, Coghill, Santosh, Romanos, Simonoff, Buitelaar, Banaschewski, Bölte, Brandeis, Buitelaar, Carucci, Coghill, Cortese, Daley, Döpfner, Ferrin, Galera, Hollis, Martin, Nagy, Purper-Ouakil, Ramos-Quiroga, Romanos, Santosh, Simonoff, Sonuga-Barke, Soutullo, Steinhausen, Thapar, Van den Hoofdakker, Van der Oord and Wong2024) with high rates of discontinuation and re-initiation (Brikell et al. Reference Brikell, Yao, Li, Astrup, Gao, Gillies, Xie, Zhang-James, Dalsgaard, Engeland, Faraone, Haavik, Hartman, Ip, Jakobsdóttir Smári, Larsson, Man, de Oliveira Costa, Pearson, Hostrup Nielsen, Snieder, Wimberley, Wong, Zhang, Zoega, Klungsøyr and Chang2024). While planned breaks – “drug holidays” – are not standard practice at ADMiRE, it is possible that periods of non-adherence occurred without the clinicians’ knowledge. Thirdly, this specialist ADHD service educates and supports clinicians in adherence to best practice guidelines in the management of adverse effects of ADHD medications, as outlined by the EAGG (Graham et al. Reference Graham, Banaschewski, Buitelaar, Coghill, Danckaerts, Dittmann, Döpfner, Hamilton, Hollis and Holtmann2011; McGrath, Reference McGrath2024). The EAGG recommends that hypertension, defined as BP > 95th percentile, should trigger either dose reduction or a drug holiday. It is plausible that cases of hypertension were actively being managed by clinicians according to these guidelines and the relatively low dose observed in this cohort supports this theory. Additional data on ADHD rating scale and side effects rating scale would have been valuable to confirm this hypothesis.
A limited number of studies have reported percentile changes in BP or HR (Landgren et al. Reference Landgren, Nasic, Johnson, Lövoll, Holmgren and Fernell2017; Conzelmann et al. Reference Conzelmann, Müller, Jans, Trott, Keil, Gerlach and Renner2019; Suess et al. Reference Suess, Chrenka, Kharbanda, Asche, O’Connor, Ekstrom and Benziger2024) with some restricting their analysis to certain threshold-based outcomes such as the presence or absence of hypertension or tachycardia (Suess et al. Reference Suess, Chrenka, Kharbanda, Asche, O’Connor, Ekstrom and Benziger2024; Vitiello et al. Reference Vitiello, Elliott, Swanson, Arnold, Hechtman, Abikoff, Molina, Wells, Wigal, Jensen, Greenhill, Kaltman, Severe, Odbert, Hur and Gibbons2012). Given that absolute HR decreases with age, the reporting of HR percentiles provides valuable clinical information. In our study we report both absolute measures and percentiles. Consistent with the expected age-related trend, the absolute HR values (bpm) did not change over the treatment period. However, there was a significant increase in HR percentiles. Tachycardia (HR > 95th percentile) warrants clinical action, including medication reduction or cessation and cardiology review if tachycardia persists. It is reassuring that only 4 participants in this cohort presented with HR > 95th percentile, indicating that the majority did not require clinical intervention.
Comparison to normal population data is an important component in the physical health monitoring of children and adolescents prescribed MPH, especially given the parental concerns regarding the longer-term effects of MPH use in children in Ireland (Flood et al. Reference Flood, Hayden, Gavin and McNicholas2019) and internationally (Brinkman et al. Reference Brinkman, Sherman, Zmitrovich, Visscher, Crosby, Phelan and Donovan2009; Charach et al. Reference Charach, Yeung, Volpe, Goodale and dosReis2014). Recent high profile media coverage of Irish CAMHS has resulted in increased parental mistrust in medication prescribing by CAMHS psychiatrists (Bond and McNicholas, Reference Bond and McNicholas2023). It is important that clinicians adhere to these guidelines and implement best practice in physical monitoring and the management of adverse effects of ADHD medications (Cortese et al. Reference Cortese, Holtmann, Banaschewski, Buitelaar, Coghill, Danckaerts, Dittmann, Graham, Taylor and Sergeant2013; Cortese, Reference Cortese2020).
This study has a number of limitations. We were unable to include a control group of non-medicated young people with ADHD as no physical health data had been collected for this cohort. The retrospective, within-subjects design allows for correlations rather than any causative conclusions. There are relatively small patient numbers in some of the between-group analyses, increasing the risk of type II error. Physical health data was analysed at two timepoints, but intermediate measurements would have provided a more accurate growth trajectory for each participant. Patients were treated with various MPH formulations (beads, osmotic release, immediate release) and it is possible that different formulations are associated with different physical health outcomes (Biederman et al. Reference Biederman, Mick, Surman, Doyle, Hammerness, Michel, Martin and Spencer2007), as most formulations are not bioequivalent due to differences in pharmacokinetics (Moharram & Kiang, Reference Moharram and Kiang2024). While we excluded participants who disclosed non-adherence at T2, we do not have data on longitudinal adherence patterns throughout the treatment period. Additional clinical factors reported to influence weight and height were not considered such as ADHD severity (Inglis et al. Reference Inglis, Carucci, Garas, Häge, Banaschewski, Buitelaar, Dittmann, Falissard, Hollis, Kovshoff, Liddle, McCarthy, Nagy, Neubert, Rosenthal, Sonuga-Barke, Wong, Zuddas and Coghill2016), depressive illness (Biederman et al. Reference Biederman, Spencer, Monuteaux and Faraone2010), socioeconomic status and parental height (Vaivada et al. Reference Vaivada, Akseer, Akseer, Somaskandan, Stefopulos and Bhutta2020). The analysis of group means did not capture the individuals who displayed larger and more clinically significant changes. Further analysis on those individuals would be needed to further elucidate clinical risk factors for growth suppression or hypertension.
Conclusion
This study is the first to examine physical health changes in Irish children with ADHD who were prescribed MPH. In line with previous studies, we found overall reductions in weight and height centiles and an increase in HR centiles in children who were prescribed MPH. Interestingly, the study results suggest that weight loss on stimulant medication is more pronounced with higher doses, but also that weight loss may attenuate with longer duration of MPH treatment. The study supports international guidelines for ongoing health monitoring and timely management of the adverse effects of MPH in children and adolescents. Future integration of digital approaches for rapid and accurate physical health monitoring, along with the early identification of concerning trends, will provide substantial support to clinicians and enhance clinical decision-making.
Funding statement
This research received no specific grant from any funding agency, commercial or not-for-profit sectors.
Competing interests
The authors declare none.
Ethical standards
The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. The authors assert that ethical approval for publication of this research study has been approved by the HSE Linn Dara CAMHS research ethics committee. Explicit informed consent was not deemed necessary by the ethics committee since this was retrospective chart review carried out for the purpose of service improvement, in the data controller’s organisation by a health practitioner employed by the data controller and the retrospective chart review was considered low risk, with highly visible transparency arrangements in place. All other safeguards required by GDPR, the Data Protection Act, 2018 and the Health Research Regulations were in place, including research ethics approval and data protection risk assessments.
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