View in EDS HTML Full Text PDF Full Text

Echocardiographic Evaluation of the Effect of Long-Term Methylphenidate Use on Cardiovascular Functions

Saved in:
Bibliographic Details
Title: Echocardiographic Evaluation of the Effect of Long-Term Methylphenidate Use on Cardiovascular Functions
Language: English
Authors: Çagatay Tunca (ORCID 0000-0001-7111-8450), Ibrahim Hakan Güllü (ORCID 0000-0003-2579-9755), Saadet Demirtas Inci (ORCID 0000-0003-2900-2926), Kamuran Kalkan (ORCID 0000-0001-6204-316X), Ruken Demirkol Tunca (ORCID 0000-0002-9195-1893), Aysegül Efe (ORCID 0000-0003-4507-6511), Ayse Nur Özkaya Ibis, Alperen Tas, Mehmet Taha Özkan (ORCID 0000-0002-7977-1785), Veysel Ozan Tanik (ORCID 0000-0002-7193-4324), Orçun Ortaköylü (ORCID 0000-0002-3846-0585), Nail Burak Özbeyaz (ORCID 0000-0002-7132-4286)
Source: Journal of Attention Disorders. 2025 29(5):326-335.
Availability: SAGE Publications. 2455 Teller Road, Thousand Oaks, CA 91320. Tel: 800-818-7243; Tel: 805-499-9774; Fax: 800-583-2665; e-mail: journals@sagepub.com; Web site: https://sagepub.com
Peer Reviewed: Y
Page Count: 10
Publication Date: 2025
Document Type: Journal Articles
Reports - Research
Descriptors: Late Adolescents, Young Adults, Attention Deficit Hyperactivity Disorder, Heart Disorders, Metabolism, Drug Use, Outcomes of Treatment, Pharmacology, Causal Models, Test Results
DOI: 10.1177/10870547241307680
ISSN: 1087-0547
1557-1246
Abstract: Objective: ADHD is one of the most common neurodevelopmental disorders, seen in children and adolescents, and is often treated with various pharmacological agents, especially methylphenidate. There are differing opinions in the literature regarding the cardiovascular safety of long-term methylphenidate use. Studies suggest that the drug may increase the risk of hypertension, myocardial infarction, ventricular arrhythmia, sudden cardiac death, cardiomyopathy, heart failure (HF), pulmonary hypertension, and stroke. This study aimed to compare the clinical and echocardiographic characteristics of patients diagnosed with ADHD who have been using long-acting methylphenidate for an extended period with age-gender matched healthy volunteers. Materials and Methods: A total of 70 patients diagnosed with ADHD, who had been using long-acting methylphenidate for 2 years or more, and 51 healthy volunteers, who were referred to our clinic, were included in our study. Patients were evaluated with basic and advanced techniques such as Motion Mode (M-mode), two-dimensional (2D), Doppler, and 2D-Speckle Tracking (STE) using transthoracic echocardiography. All other data were evaluated instantly after the processing with the strain images analysis program. Results: Statistically significant differences were observed between the case and control groups in terms of body mass index (BMI) and systolic blood pressure (SBP), with BMI negatively correlated and SBP positively correlated with methylphenidate use duration. There was no significant difference between the groups in apical four-chamber, three-chamber, two-chamber, and global longitudinal strain (GLS) values obtained by 2D-STE technique indicating early deterioration. The Left Ventricular (LV) lateral E' value, which indicates diastolic dysfunction, was lower in the drug group, but still within normal limits. The lateral LV E', Right Ventricular (RV) E', and RV A' values showed a significant negative correlation with the duration of drug use and remained within normal limits. Other parameters evaluating systolic/diastolic function such as E/E', left ventricular ejection fraction (LVEF), myocardial performance index (MPI), and tricuspid/mitral annular plane systolic excursion (TAPSE/MAPSE) did not differ significantly between the groups and were within normal limits. Valve structures and regurgitations were also not significantly different between the two groups. Conclusion: Considering all parameters, we conclude that long-term use of long-acting methylphenidate does not cause cardiovascular dysfunction in late adolescent and early adult individuals. The observed differences in the E' lateral value between the case and control groups, as well as the slight correlation of lateral LV E', RV E', and RV A' values with the duration of use, do not directly indicate cardiac dysfunction.
Abstractor: As Provided
Entry Date: 2025
Accession Number: EJ1467552
Database: ERIC
Full text is not displayed to guests.
FullText Links:
  – Type: pdflink
    Url: https://content.ebscohost.com/cds/retrieve?content=AQICAHj0k_4E0hTGH8RJwT4gCJyBsGNe_WN95AvKlDbXJGqwxwFFYYUdF9448NC5oGc4-9HhAAAA4jCB3wYJKoZIhvcNAQcGoIHRMIHOAgEAMIHIBgkqhkiG9w0BBwEwHgYJYIZIAWUDBAEuMBEEDDrPbjWoK_X8LyEWfwIBEICBmigMoRi8nChniRQRtum6DxNTYAZCymo5MRXr7OU50DjbBGRXqiZRbBaYVkBbWc6aeUb6DATweKifM-RrPX4VGJi_GGIBXQkAzmVtfbv_y8Bt84IS6Lxbi5XDfgE4N-vJsEZTQkQ1d5YCtTr0_lXDszke1k3RD9L2r_TLOihM5mEdM4gvyS2u4gAYwdzML1YqOTEcvoMlzUDp_og=
Text:
  Availability: 1
  Value: <anid>AN0182791760;gs001mar.25;2025Feb07.01:27;v2.2.500</anid> <title id="AN0182791760-1">Echocardiographic Evaluation of the Effect of Long-Term Methylphenidate Use on Cardiovascular Functions </title> <p>Objective: ADHD is one of the most common neurodevelopmental disorders, seen in children and adolescents, and is often treated with various pharmacological agents, especially methylphenidate. There are differing opinions in the literature regarding the cardiovascular safety of long-term methylphenidate use. Studies suggest that the drug may increase the risk of hypertension, myocardial infarction, ventricular arrhythmia, sudden cardiac death, cardiomyopathy, heart failure (HF), pulmonary hypertension, and stroke. This study aimed to compare the clinical and echocardiographic characteristics of patients diagnosed with ADHD who have been using long-acting methylphenidate for an extended period with age-gender matched healthy volunteers. Materials and Methods: A total of 70 patients diagnosed with ADHD, who had been using long-acting methylphenidate for 2 years or more, and 51 healthy volunteers, who were referred to our clinic, were included in our study. Patients were evaluated with basic and advanced techniques such as Motion Mode (M-mode), two-dimensional (2D), Doppler, and 2D-Speckle Tracking (STE) using transthoracic echocardiography. All other data were evaluated instantly after the processing with the strain images analysis program. Results: Statistically significant differences were observed between the case and control groups in terms of body mass index (BMI) and systolic blood pressure (SBP), with BMI negatively correlated and SBP positively correlated with methylphenidate use duration. There was no significant difference between the groups in apical four-chamber, three-chamber, two-chamber, and global longitudinal strain (GLS) values obtained by 2D-STE technique indicating early deterioration. The Left Ventricular (LV) lateral E′ value, which indicates diastolic dysfunction, was lower in the drug group, but still within normal limits. The lateral LV E′, Right Ventricular (RV) E′, and RV A′ values showed a significant negative correlation with the duration of drug use and remained within normal limits. Other parameters evaluating systolic/diastolic function such as E/E′, left ventricular ejection fraction (LVEF), myocardial performance index (MPI), and tricuspid/mitral annular plane systolic excursion (TAPSE/MAPSE) did not differ significantly between the groups and were within normal limits. Valve structures and regurgitations were also not significantly different between the two groups. Conclusion: Considering all parameters, we conclude that long-term use of long-acting methylphenidate does not cause cardiovascular dysfunction in late adolescent and early adult individuals. The observed differences in the E′ lateral value between the case and control groups, as well as the slight correlation of lateral LV E′, RV E′, and RV A′ values with the duration of use, do not directly indicate cardiac dysfunction.</p> <p>Keywords: methylphenidate; ADHD; strain echoardiography</p> <hd id="AN0182791760-2">Introduction</hd> <p>One of the most commonly diagnosed and pharmacologically treated neurodevelopmental disorders in children and adolescents is ADHD. According to recent data, the global prevalence of ADHD is approximately 7.2% among children and adolescents and around 3.4% among adults ([<reflink idref="bib2" id="ref1">2</reflink>]; [<reflink idref="bib22" id="ref2">22</reflink>]). Psychostimulant medications have been observed to significantly improve the ADHD symptoms of physical hyperactivity and inability to maintain focus in children and adults ([<reflink idref="bib5" id="ref3">5</reflink>]; [<reflink idref="bib19" id="ref4">19</reflink>]; [<reflink idref="bib24" id="ref5">24</reflink>]). All ADHD medications carry warnings in their package inserts about potential serious adverse cardiovascular reactions.</p> <p>Most drugs used to treat ADHD are sympathomimetic amines with similar chemical structures and physiological activities. These compounds have stimulant effects on the central nervous system by increasing noradrenaline and dopamine levels in the prefrontal cortex and may cause an increase in resting heart rate (HR) and blood pressure (BP) by stimulating adrenergic receptors in the heart and blood vessels ([<reflink idref="bib17" id="ref6">17</reflink>]). These include methylphenidate, amphetamine, lysdexamphetamine, atomoxetine, and methamphetamine ([<reflink idref="bib7" id="ref7">7</reflink>]).</p> <p>From a physiopathological point of view, chronic excessive sympathetic nervous system activity increases the workload of the heart and causes hypertension, endothelial dysfunction, left ventricular (LV) hypertrophy, and arrhythmia episodes ([<reflink idref="bib3" id="ref8">3</reflink>]).Vagal activity, on the other hand, provides a vasodilatory effect, reduces BP and improves HR variability. Patients treated for ADHD are mostly young and cardiovascularly healthy, most of the published studies are of short duration and report few adverse effects ([<reflink idref="bib9" id="ref9">9</reflink>]). Due to the mention of effects, health professionals and the rest of the population believe that sympathomimetic amines have no adverse cardiovascular effects. However, other sympathomimetic drugs used for asthma, heart failure (HF), and hypotension have been associated with an increased risk of events, particularly in those with existing cardiovascular disease ([<reflink idref="bib6" id="ref10">6</reflink>]; [<reflink idref="bib8" id="ref11">8</reflink>]).</p> <p>With standard echocardiographic techniques, only the radial contractility of the myocardium can be evaluated to a limited extent. Using the strain technique, regional and global myocardial function can be evaluated more comprehensively and reliably. The movement of LV segments at different speeds and amounts leads to the concept of deformation. This deformation is described by the term strain in echocardiography. In early myocardial diseases, the decrease in longitudinal function is compensated by radial and circumferential compensation and left ventricular ejection fraction (LVEF) is maintained within normal limits. The advantage of strain imaging is that it can detect even minimal changes in cardiac function, allowing quantitative assessment of LV global and regional myocardial function in early stages. The predictive value of global longitudinal strain (GLS) has been demonstrated in various cardiovascular pathologies including coronary artery disease, myocardial infarction, stroke, HF, valvular heart disease, atrial fibrillation, cardiomyopathy, cardiotoxicity, congenital heart disease and pulmonary hypertension ([<reflink idref="bib1" id="ref12">1</reflink>]; [<reflink idref="bib11" id="ref13">11</reflink>]).</p> <p>In this study, we aimed to investigate whether there would be any difference in myocardial functions of the group using methylphenidate with long-term increased sympathetic nervous system activation by strain imaging method when compared with the healthy control group, and to investigate the relationship of the changes, if any, with the total duration of use.</p> <hd id="AN0182791760-3">Materials and Methods</hd> <p>The study, which was approved by the Clinical Research Ethics Committee, was designed as a case-control study. Verbal and written consent was obtained from patients and healthy volunteers for participation in the study.</p> <p>Patients diagnosed with ADHD according to DSM-5 diagnostic criteria and using methylphenidate and healthy volunteers including age and gender matched doctors, nurses, and nurse interns working in our hospital were included in the study. A psychiatric interview was conducted with the patients and their families who volunteered to participate in the study and gave consent, in order to confirm the diagnosis of ADHD and evaluate any accompanying psychiatric disorders. During the psychiatric interview, accompanying psychiatric disorders were determined according to DSM-5 diagnostic criteria by applying the semi-structured diagnostic scale, Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). The socioeconomic status (SES) of the groups was determined by inquiring about the families' annual income and categorizing it based on the income levels defined for that year in the study's country. No standardized measurement tools (e.g., socioeconomic status scales) were utilized in assessing SES. A total of 129 people were included in our study, of which 76 belonged to the methylphenidate use group and 53 belonged to the control group. Four patients and 2 controls with insufficient image quality for strain, 1 patient with mild to moderate mitral regurgitation due to mitral valve prolapse, and 1 patient with athlete's heart characteristics were excluded from the study. Of the remaining 121 individuals, 70 belonged to the case group and 51 to the control group. Routine anamnesis was taken and physical examination was performed. Systolic-diastolic BPs, HRs, height, and weight were measured and recorded.</p> <hd id="AN0182791760-4">Inclusion Criteria</hd> <p></p> <ulist> <item> -Patients diagnosed with ADHD aged 16 to 30 years with regular long-acting methylphenidate use for 2 years or more.</item> <p></p> <item> -For patients aged 16 to 18 years, the patient and his/her parents agree to participate in the study.</item> </ulist> <hd id="AN0182791760-5">Use Regular Medication</hd> <p>Patients who did not discontinued their medication for more than one more month and used it regularly every day were included. Medications Usage information was confirmed by their parents and the prescription data system.</p> <hd id="AN0182791760-6">Exclusion Criteria</hd> <p></p> <ulist> <item> - Presence of any known cardiovascular disease prior to the use of methylphenidate</item> <p></p> <item> - Presence of a comorbid psychiatric disorder meeting DSM-5 diagnostic criteria</item> <p></p> <item> - Patients taking medication for a chronic disease, other than methylphenidate</item> <p></p> <item> - Having medication holiday periods while using methylphenidate</item> <p></p> <item> - Long-term use of any other medication (>6 months)</item> <p></p> <item> - Presence of any medication use of the participants in the control group</item> </ulist> <p>The K-SADS-PL was administered to children, adolescents, and their parents by a child and adolescent psychiatrist to identify comorbid psychiatric disorders in the study group and to exclude children and adolescents with psychiatric disorders in the healthy control group ([<reflink idref="bib16" id="ref14">16</reflink>]; [<reflink idref="bib21" id="ref15">21</reflink>]).</p> <hd id="AN0182791760-7">Echocardiography</hd> <p>The study participants underwent comprehensive echocardiographic assessment utilizing the Philips EPIQ 7 Ultrasound System, conducted by two proficient investigators in accordance with the guidelines of the American Society of Echocardiography and the European Association of Echocardiography ([<reflink idref="bib13" id="ref16">13</reflink>]). The evaluation encompassed the measurement of aortic diameter, aortic annulus, and left atrial diameter in the parasternal long-axis view using Motion Mode (M-Mode). Additionally, LV end-systolic and end-diastolic diameters, interventricular septum at end-diastole, and LV posterior wall thickness were quantified.</p> <p>All valves stenosis and regurgitation were assessed using color Doppler imaging. The ejection fraction, along with the integrity of the interatrial septum and pulmonary valve, was evaluated in the parasternal short-axis view. The LVEF was calculated employing the biplane Simpson method from apical four-chamber views. Transmitral flow pattern (E, A, E/A, and Deceleration Time) was calculated by placing the pulse wave Doppler at the tip of the mitral valves. Annular velocities (systolic flow velocity (S′), early diastolic flow velocity (E′), and late diastolic flow velocity (A′)) in the left and right ventricles were evaluated with tissue Doppler imaging function. The myocardial performance index (MPI) for the LV was determined using isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT), and ejection time (ET). Mitral and tricuspid annular plane systolic excursion (MAPSE/TAPSE) was measured using M-Mode images. Systolic pulmonary artery pressure sPAP was estimated using continuous wave Doppler, based on the modified Bernoulli equation. GLS was assessed using speckle-tracking echocardiography, with data acquisition at a frequency of 60 to 80 Hz during three consecutive cardiac cycles.</p> <p>Analysis was performed using the Philips QLAB-CMQ software, where LV endocardial borders were manually delineated and epicardial borders were automatically defined. The region of interest (ROI) was confirmed by the software, ensuring inclusion of the entire LV wall thickness. Each parameter was measured at least three times, and the average was used for statistical analysis.</p> <p>Echocardiographic images were segmented into 17 regions for detailed analysis: the septal and lateral walls from apical four-chamber views, the posterior and anteroseptal walls from apical three-chamber views, and the inferior and anterior walls from apical two-chamber views. Each wall was further divided into apical, middle, and basal segments. Peak systolic and peak longitudinal strain values for each segment were recorded, and GLS was calculated as the average of peak systolic strain values from all 18 segments. Figure 1 illustrates the standard echocardiographic segments, while Figure 2 depicts the measurement of GLS.</p> <p>Graph: Figure 1. Standardized myocardial segmentation and nomenclature for echocardiography. The left ventricle is divided into 17 segments for 2D echocardiography. One can identify these segments in multiple views.</p> <p>Graph: Figure 2. Longitudinal peak strain value, time curve of left ventricular (LV) segments in apical four-chamber section and Bull's eye plot of the LV. It gives information about how well the LV wall segments contract. Contractility is shown both as colors and as global longitudinal strain (GLS) values. In general, contraction weakens as the colors change from red to blue. In healthy individuals, GLS values between 18% and 22% in absolute value are considered normal. Higher values can be seen in young people.</p> <hd id="AN0182791760-8">Statistical Analysis</hd> <p>Categorical data are given as number and percentage. Continuous variables were expressed as mean ± standard deviation (mean ± SD or median (minimum–maximum) depending on normal or abnormal distribution. Chi-square test was used to analyze non-parametric data. Before analyzing the statistical significance of all parametric data, Kolmogorov-Smirnov test for normality and Levene test for homogeneity were performed. Parametric data showing normal distribution were analyzed by independent groups <emph>t</emph>-test, and parametric data not showing Results normal distribution were analyzed by Mann-Whitney <emph>U</emph> test. The relationships between independent numerical variables were evaluated using Pearson correlation if they were in accordance with normal distribution and Spearman correlation analyses if they were not. In all analyses, a two-way <emph>p</emph> <.05 was accepted as significant. SPSS (IBM Corp., Armonk, NY, USA) package program was used for all analyses.</p> <hd id="AN0182791760-9">Results</hd> <p>The mean age of the study group was 20 ± 3 years and 39.6% were female (<emph>n</emph> = 48). When the sociodemographic characteristics of the groups were evaluated, no statistically significant differences were found between the groups in terms of age, sex, and socioeconomic status. The mean body mass index (BMI) was 23.1 ± 3.9. Systolic and diastolic BPs were 118.9 ± 12 and 74.6 ± 5.2, respectively. HR was 82 ± 10.2. The case and control groups were similar in terms of age and sex. About 61.4% of the case group and 58.8% of the control group were male. There was a statistically significant difference between the two groups in terms of BMIs. It was 22 ± 4 in the case group and 24 ± 3.5 in the control group (<emph>p</emph> <.05). A statistically significant difference was found between the two groups in terms of systolic blood pressures (SBP). It was 120.8 ± 12.1 mmHg in the case group and 116.6 ± 11.3 mmHg in the control group (<emph>p</emph> <.05). No significant difference was found between the groups in terms of diastolic blood pressures (DBP). HR was higher in the case group (83.4 ± 9.4 mmHg) compared to the control group (80.7 ± 11 mmHg) but did not reach statistical significance. The mean duration of long-acting methylphenidate use in the case group was 51 months, the shortest being 29 and the longest 108 months. Table 1 shows the demographic characteristics and methylphenidate doses of the study groups.</p> <p>Table 1. Comparison of Demographic Characteristics of the Case and Control Groups Included in the Study.</p> <p>Graph</p> <p> <ephtml> <table><colgroup><col align="left" /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /></colgroup><thead><tr><th align="left">Variables</th><th align="center">All population</th><th align="center">Case</th><th align="center">Control</th><th align="center"><italic>p</italic> value</th></tr></thead><tbody><tr><td>Age</td><td>20.07 ± 3.05</td><td>19.72 ± 2.71</td><td>20.54 ± 3.42</td><td>.145</td></tr><tr><td>Sex, <italic>n</italic> (%) female</td><td>48 (39.6)</td><td>27 (38.6%)</td><td>21 (41.2%)</td><td>.851</td></tr><tr><td>BMI, kg/m2</td><td>23.14 ± 3.92</td><td>22.50 ± 4.05</td><td>24.03 ± 3.58</td><td>.034</td></tr><tr><td>SBP, mmHg</td><td>118.92 ± 12.01</td><td>120.87 ± 12.16</td><td>116.25 ± 11.38</td><td>.036</td></tr><tr><td>DBP, mmHg</td><td>74.65 ± 5.25</td><td>74.67 ± 5.47</td><td>74.62 ± 4.98</td><td>.964</td></tr><tr><td>HR, bpm</td><td>82.37 ± 10.21</td><td>83.58 ± 9.48</td><td>80.71 ± 11.01</td><td>.127</td></tr><tr><td>SES <italic>n</italic> (%)</td><td /><td /><td /><td /></tr><tr><td>Low</td><td>24 (19.83)</td><td>15 (21.43)</td><td>9 (17.65)</td><td>.140</td></tr><tr><td>Medium</td><td>74 (61.16)</td><td>38 (54.29)</td><td>36 (70.59)</td><td /></tr><tr><td>High</td><td>23 (19.01)</td><td>17 (24.28)</td><td>6 (11.76)</td><td /></tr><tr><td>Methylphenidate dose (mg/day)</td><td /><td /><td /><td /></tr><tr><td>Female (mean ± <italic>SD</italic>)</td><td /><td>33.00 ± 15.787</td><td /><td>.666</td></tr><tr><td>Male (mean ± <italic>SD</italic>)</td><td /><td>35.79 ± 14.364</td><td /><td /></tr><tr><td>Duration of use (month)</td><td /><td /><td /><td /></tr><tr><td>Mean (shortest-longest)</td><td /><td>51 (29–108)</td><td /><td /></tr></tbody></table> </ephtml> </p> <p>1 <emph>Note</emph>. BMI = Body mass index; SBP = systolic blood pressure; DBP = diastolic blood pressure; HR = heart rate; SES = socioeconomic status.</p> <p>Conventional echocardiographic characteristics of the case and control group patients were compared. All parameters were within normal limits and there was no statistically significant difference between the two groups (Table 2).</p> <p>Table 2. Comparison of Conventional Echocardiographic Characteristics of the Case and Control Groups Included in the Study.</p> <p>Graph</p> <p> <ephtml> <table><colgroup><col align="left" /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /></colgroup><thead><tr><th align="left">Variables</th><th align="center">All population</th><th align="center">Case</th><th align="center">Control</th><th align="center"><italic>p</italic> value</th></tr></thead><tbody><tr><td>LVEF, %</td><td>64.14 ± 3.77</td><td>63.72 ± 3.41</td><td>64.67 ± 4.21</td><td>.174</td></tr><tr><td>Annulus aorta, cm</td><td>1,79 ± 0,19</td><td>1.79 ± 0.21</td><td>1.79 ± 01.19</td><td>.928</td></tr><tr><td>Ascending aorta, cm</td><td>2.64 ± 0.27</td><td>2.63 ± 0.31</td><td>2.66 ± 0.23</td><td>.541</td></tr><tr><td>Left atrial dia, cm</td><td>2.85 ± 0.34</td><td>2.82 ± 0.32</td><td>2.88 ± 0.31</td><td>.389</td></tr><tr><td>LVED dia, cm</td><td>3.95 ± 0.32</td><td>3.92 ± 0.33</td><td>3.99 ± 0.31</td><td>.225</td></tr><tr><td>LVES dia, cm</td><td>2.78 ± 0.27</td><td>2.76 ± 0.26</td><td>2.81 ± 0.29</td><td>.382</td></tr><tr><td>Septal WT, cm</td><td>0.75 ± 0.1</td><td>0.74 ± 0.07</td><td>0.76 ± 0.06</td><td>.308</td></tr><tr><td>Posterior WT, cm</td><td>0.71 ± 0.1</td><td>0.71 ± 0.08</td><td>0.72 ± 0.09</td><td>.221</td></tr><tr><td>Mitral E, cm/s</td><td>94.86 ± 15.1</td><td>96.99 ± 12.83</td><td>93.32 ± 16.31</td><td>.185</td></tr><tr><td>Mitral A, cm/s</td><td>62.07 ± 10.3</td><td>60.82 ± 10.62</td><td>63.78 ± 9.66</td><td>.118</td></tr><tr><td>E/A</td><td>1.54 ± 0.22</td><td>1.55 ± 0.23</td><td>1.53 ± 0.21</td><td>.723</td></tr><tr><td>Mitral deceleration time, ms</td><td>159.76 ± 25.21</td><td>161.2 ± 25.5</td><td>157.8 ± 24.9</td><td>.467</td></tr><tr><td>Aortic valve vel, m/s</td><td>1.27 ± 0.23</td><td>1.25 ± 0.21</td><td>1.29 ± 0.18</td><td>.268</td></tr><tr><td>Pulmonary valve vel, m/s</td><td>0.94 ± 0.16</td><td>0.92 ± 0.16</td><td>0.97 ± 0.15</td><td>.106</td></tr><tr><td>Tricuspid valve vel, m/s</td><td>1.34 ± 0.56</td><td>1.35 ± 0.55</td><td>1.33 ± 0.56</td><td>.875</td></tr><tr><td>Pulmonary acceleration time, ms</td><td>149.53 ± 21.79</td><td>152.22 ± 22.37</td><td>144.56 ± 20.35</td><td>.056</td></tr><tr><td>sPAP, mmHg</td><td>11.82 ± 6.56</td><td>11.92 ± 6.53</td><td>11.68 ± 6.67</td><td>.842</td></tr><tr><td>TAPSE, cm</td><td>2.11 ± 0.28</td><td>2.15 ± 0.28</td><td>2.05 ± 0.27</td><td>.072</td></tr><tr><td>MAPSE, cm</td><td>2.36 ± 0.34</td><td>2.32 ± 0.30</td><td>2.42 ± 0.38</td><td>.138</td></tr></tbody></table> </ephtml> </p> <p>2 <emph>Note</emph>. LVEF = left ventricular ejection fraction; LV = left ventricle; RV = right ventricle; LVED = left ventricle end-diastolic; LVES = left ventricle end-systolic; E = early diastolic peak rate; A = late diastolic peak rate; Vel = velocity; sPAP = systolic pulmonary artery pressure; TAPSE = systolic excursion of the tricuspid valve in the annular plane; MAPSE = mitral valve systolic excursion in annular plane.</p> <p>Tissue Doppler echocardiographic features of the case and control group patients included in the study were compared (Table 3). All parameters were within normal limits, and a statistically significant difference was detected between the two groups in terms of LV E′ (Lateral) value. It was 18.6 ± 2.9 in the case group and 20.4 ± 3.6 in the control group (<emph>p</emph> <.05). No statistically significant difference was found between the groups in terms of other parameters. The strain (deformation) parameters of the case and control group patients were compared (Table 4). All parameters are within normal limits and there is no parameter that creates a statistically significant difference between the two groups.</p> <p>Table 3. Comparison of Tissue Doppler Echocardiographic Characteristics of the Case and Control Groups Included in the Study.</p> <p>Graph</p> <p> <ephtml> <table><colgroup><col align="left" /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /></colgroup><thead><tr><th align="left">Variables</th><th align="center">All population</th><th align="center">Case</th><th align="center">Control</th><th align="center"><italic>p</italic> value</th></tr></thead><tbody><tr><td>IVCT, ms</td><td>68.67 ± 7.18</td><td>69.51 ± 6.72</td><td>67.52 ± 7.68</td><td>.134</td></tr><tr><td>IVRT, ms</td><td>74.75 ± 9.64</td><td>74.71 ± 8.81</td><td>74.80 ± 10.99</td><td>.962</td></tr><tr><td>ET, ms</td><td>263.57 ± 20.11</td><td>263.44 ± 21.72</td><td>263.74 ± 17.86</td><td>.935</td></tr><tr><td>LV MPI</td><td>0.54 ± 0.05</td><td>0.54 ± 0.05</td><td>0.54 ± 0.06</td><td>.763</td></tr><tr><td>LV E′ (Lat), cm/s</td><td>19.42 ± 3.43</td><td>18.62 ± 2.99</td><td>20.48 ± 3.66</td><td>.003</td></tr><tr><td>LV A′ (Lat), cm/s</td><td>9.57 ± 2.88</td><td>9.32 ± 2.91</td><td>9.91 ± 2.82</td><td>.264</td></tr><tr><td>LV S′ (Lat), cm/s</td><td>9.06 ± 1.68</td><td>12.12 ± 2.43</td><td>13.02 ± 2.53</td><td>.054</td></tr><tr><td>LV E′ (Med), cm/s</td><td>13.26 ± 2.26</td><td>13.32 ± 2.23</td><td>13.19 ± 2.31</td><td>.752</td></tr><tr><td>LV A′ (Med), cm/s</td><td>8.05 ± 1.79</td><td>8.01 ± 1.95</td><td>8.12 ± 1.55</td><td>.729</td></tr><tr><td>LV S′ (Med), cm/s</td><td>9.06 ± 1.68</td><td>9.03 ± 1.58</td><td>9.10 ± 1.82</td><td>.822</td></tr><tr><td>RV E′ (Lat), cm/s</td><td>17.19 ± 4.09</td><td>16.58 ± 3.91</td><td>18.03 ± 4.21</td><td>.056</td></tr><tr><td>RV A′ (Lat), cm/s</td><td>10.59 ± 2.67</td><td>8.01 ± 1.95</td><td>8.12 ± 1.55</td><td>.097</td></tr><tr><td>RV S′ (Lat), cm/s</td><td>12.18 ± 1.43</td><td>12.06 ± 1.49</td><td>12.35 ± 1.36</td><td>.275</td></tr><tr><td>E/E′ mean</td><td>6.14 ± 1.17</td><td>6.15 ± 1.39</td><td>6.13 ± 0.78</td><td>.924</td></tr></tbody></table> </ephtml> </p> <p>3 <emph>Note</emph>. LV = left ventricle; RV = right ventricle; Lat = lateral; Med = medial; E = early diastolic peak rate; A = late diastolic peak rate; IVCT = isovolumetric contraction time; IVRT = isovolumetric relaxation time; ET = ejection time; MPI = myocardial performance index; E′ = early diastolic annular motion; A′ = late diastolic annular motion; S′ = systolic annular motion.</p> <p>Table 4. Comparison of Strain Echocardiographic Characteristics of the Case and Control Groups Included in the Study.</p> <p>Graph</p> <p> <ephtml> <table><colgroup><col align="left" /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /><col align="char" char="." /></colgroup><thead><tr><th align="left">Variables</th><th align="center">All population</th><th align="center">Case</th><th align="center">Control</th><th align="center"><italic>p</italic> value</th></tr></thead><tbody><tr><td>LVS 4C, %</td><td>23.16 ± 2.27</td><td>23.18 ± 2.03</td><td>23.15 ± 2.59</td><td>.946</td></tr><tr><td>LVS 3C, %</td><td>23.25 ± 2.13</td><td>23.42 ± 1.74</td><td>23.02 ± 2.57</td><td>.311</td></tr><tr><td>LVS 2C, %</td><td>22.44 ± 3.43</td><td>22.60 ± 3.17</td><td>22.23 ± 3.78</td><td>.568</td></tr><tr><td>GLS, %</td><td>23.11 ± 1.91</td><td>23.24 ± 1.78</td><td>22.94 ± 2.07</td><td>.397</td></tr></tbody></table> </ephtml> </p> <p>4 <emph>Note</emph>. LVS 4C = four chamber left ventricular strain; LVS 3C = three chamber left ventricular strain; LVS 2C = two chamber left ventricular strain; GLS = global longitudinal strain.</p> <p>Correlation analyses were performed between the duration of methylphenidate use and clinical and echocardiographic data of the case group included in our study. A statistically significant correlation was found between BMI, SBP, LV E′ (Lateral), RV E′ and A′ (Lateral) values, and duration of methylphenidate use (<emph>p</emph> <.05; Table 5). Figure 3 shows the scatter-plot diagram of these parameters.</p> <p>Table 5. Correlation Between Duration of Medication Use and Echocardiographic and Clinical Parameters.</p> <p>Graph</p> <p> <ephtml> <table><colgroup><col align="left" /><col align="char" char="." /><col align="char" char="." /></colgroup><thead><tr><th align="left">Variables</th><th align="center">(ρ) (rho)</th><th align="center"><italic>p</italic> value</th></tr></thead><tbody><tr><td>BMI</td><td><bold>−.258</bold></td><td>.004</td></tr><tr><td>SBP</td><td>.<bold>289</bold></td><td>.001</td></tr><tr><td>LV E′</td><td><bold>−.205</bold></td><td>.024</td></tr><tr><td>RV E′</td><td>.214</td><td>.018</td></tr><tr><td>RV A′</td><td>−.180</td><td>.024</td></tr></tbody></table> </ephtml> </p> <p>5 <emph>Note</emph>. BMI = Body mass index; SBP = systolic blood pressure; LV = left ventricle; RV = right ventricle; E′ = early diastolic annular motion; A′ = late diastolic annular motion.</p> <p>DIAGRAM: Figure 3. Scatter-dot diagram of data blinded by duration of medication use. Note. BMI = Body mass index; SBP = systolic blood pressure; LV = left ventricle; RV = right ventricle; E′ = early diastolic annular motion; A′ = late diastolic annular motion; DMU = duration of medication use.</p> <hd id="AN0182791760-10">Discussion</hd> <p>This study is the first to investigate the effects of long-term, long-acting methylphenidate use on myocardial function in late adolescence and early adulthood using both basic and advanced echocardiographic techniques, including M-Mode, 2D, Doppler, and strain. The principal finding suggests that prolonged administration of long-acting methylphenidate does not precipitate cardiovascular dysfunction, defined in terms of contraction and relaxation mechanisms, in these individuals, as demonstrated by detailed echocardiographic evaluations.</p> <p>In our study, contrary to our expectations, no significant differences were found between the case and control groups in apical four-chamber, three-chamber, two-chamber, and GLS values. Additionally, there was no significant correlation between the duration of drug use and strain values. The literature lacks studies examining the use of drugs such as amphetamine, lisdexamphetamine, atomoxetine, and methamphetamine, currently used in the treatment of ADHD, with the strain technique. In a study by [<reflink idref="bib28" id="ref17">28</reflink>] investigating potential cardiovascular abnormalities in asymptomatic amphetamine addicts using 3D-STE, no significant differences were found between the groups in LVEF, LVESV, LVEDC, E/A, E/E′, and global radial strain (GRS) values. In 2D-STE analyses conducted with ergot and non-ergot dopaminergic drugs used in Parkinson's disease treatment, no significant difference was observed between the groups, similar to the results of our study ([<reflink idref="bib20" id="ref18">20</reflink>]).</p> <p>In our study, the BMI in the methylphenidate group was found to be lower compared to the control group, which is thought to be due to the drug's appetite-suppressing effect and increased physical activity. There is no strong evidence that low BMI in young adults has a significant impact on cardiovascular outcomes ([<reflink idref="bib10" id="ref19">10</reflink>]; [<reflink idref="bib23" id="ref20">23</reflink>]).</p> <p>Similar to earlier research, our study confirmed that amphetamines and methylphenidate elevate resting HR and SBP ([<reflink idref="bib26" id="ref21">26</reflink>]). A meta-analysis of 10 clinical studies found that ADHD medications raised resting HR by 5 to 7 bpm and SBP by about 2 mmHg ([<reflink idref="bib15" id="ref22">15</reflink>]). Epidemiological studies have associated increased resting HR with higher rates of cardiovascular disease and mortality, though data on risks specific to pharmacologically induced increases remain limited ([<reflink idref="bib18" id="ref23">18</reflink>]; [<reflink idref="bib27" id="ref24">27</reflink>]). A randomized controlled trial reported a fourfold increase in prehypertension risk among previously normotensive adults on methylphenidate ([<reflink idref="bib18" id="ref25">18</reflink>]). In our study, we observed a statistically significant difference in SBP between the case and control groups, but no difference in DBP.</p> <p>E′ and A′ waves, key parameters in tissue Doppler echocardiography, assess diastolic function, with E′ indicating passive ventricular relaxation in early diastole and A′ showing atrial contraction's impact on late diastolic filling. Lower values for both suggest advanced diastolic dysfunction affecting passive and active ventricular filling ([<reflink idref="bib13" id="ref26">13</reflink>]). In our study, LV E′ (Lateral) in the case group was significantly lower than in controls but remained normal (18.62 ± 2.99 vs. 20.48 ± 3.66, <emph>p</emph> <.05). RV E′ (Lateral) and RV A′ (Lateral) values also correlated negatively with drug duration, remaining within normal limits. [<reflink idref="bib12" id="ref27">12</reflink>] similarly found only LV E′ (Septal) to differ significantly, with lower yet normal values in the methylphenidate group.</p> <p>Methylphenidate is known to increase cardiac contractility through its dopaminergic effects, while dopamine is recognized for raising left ventricular filling pressures. In an animal study by Take et al., administration of methylphenidate resulted in a dose-dependent increase in D2 receptor expression in myocytes ([<reflink idref="bib25" id="ref28">25</reflink>]). Lang et al. suggested that the observed increase in left ventricular filling pressures with dopamine may be attributable to arterial vasoconstriction mediated via alpha-adrenoceptor activation ([<reflink idref="bib14" id="ref29">14</reflink>]). In our study, no significant difference was observed in the E/E′ values, indicative of filling pressure (<emph>p</emph> =.924); however, we hypothesize that the differences in E′ values may be linked to the peripheral effects of methylphenidate.</p> <p>This study includes a variety of parameters that are particularly sensitive to early-stage cardiac abnormalities. To assess left ventricular systolic functions, LVEF, MAPSE, and LV S′ were evaluated; for assessing left ventricular filling and diastolic functions, E and A waves, the E/A ratio, and deceleration time were included. Additionally, TAPSE and RV S′ were utilized to evaluate right ventricular systolic functions, along with the myocardial performance index (MPI), which provides an integrated measure of global ventricular function <sups>16</sups>. All parameters remained within normal limits, and there were no statistically significant differences observed either between groups or in relation to drug duration (<emph>p</emph> >.05).</p> <p>The goal of treatment remains to find the optimal dose of methylphenidate that effectively manages symptoms with minimal side effects. Unlike in heart failure management, increasing pharmacological agents to the highest tolerable dose is not warranted in ADHD treatment. Current guidelines suggest a daily methylphenidate dose of 0.4 to 1.4 mg/kg, with a maximum of 72 mg/day recommended for adolescents (13–17 years) and adults (18–65 years). In our study, the average dose was 0.98 mg/kg, with no significant association observed between effective doses and clinical or echocardiographic data. Future studies utilizing higher doses may help clarify whether dose-dependent effects influence these finding</p> <p>Considering all parameters, we think that the drug does not cause cardiovascular dysfunction in individuals in late adolescence and early adulthood in whom we examined long-term long-acting methylphenidate use, and that the E′ lateral value, which shows a difference between the case and control groups, and the LV E′ (Lateral), RV E′ (Lateral), and RV A′ (Lateral) values, which are very weakly correlated with the duration of use, do not directly reflect diastolic dysfunction (ρ = −.205, −.214, and −.180, respectively). Large retrospective cohort studies also support a lack of association between methylphenidate use and serious cardiovascular events in both children and adults, with six out of seven population-based studies reporting no link between psychostimulant use and adverse cardiovascular outcomes ([<reflink idref="bib4" id="ref30">4</reflink>]).</p> <hd id="AN0182791760-11">Limitations</hd> <p>Our findings on the cardiovascular effects of methylphenidate are subject to several limitations. The case-control design restricts causal inference, and the lack of standardized timing for clinical and echocardiographic evaluations may introduce variability affecting the results. Cardiovascular assessments were largely limited to ECG and BP measurements unless significant symptoms or family histories warranted further evaluation, potentially missing subtle but clinically relevant cardiac changes induced by methylphenidate.</p> <p>Although our sample size was supported by a power analysis for initial statistical confidence, the relatively small cohort of 69 patients may not reveal more nuanced effects or allow broad generalization of the findings. Additionally, variability in drug use duration (29–108 months) adds heterogeneity to the results. Future studies should aim to include larger, more diverse cohorts with more consistent treatment durations to better assess the long-term cardiovascular impacts of methylphenidate.</p> <hd id="AN0182791760-12">Conclusion</hd> <p>In our study, we compared the clinical and echocardiographic characteristics of ADHD patients on long-term, long-acting methylphenidate with age- and sex-matched healthy volunteers. In the medication group, the LV E′ value, while within normal limits, was significantly lower, with higher SBP and lower BMI, though the increase in HR did not reach statistical significance. As the duration of use increased, lateral LV E′, RV E′, and A′ values showed a statistically significant decrease, although still within normal limits. Duration of use was correlated with both SBP and BMI. Critical measurements, including GLS, MPI, ejection fraction, E/A, E/E′, S′, TAPSE, MAPSE, and LV dimensions, remained within normal ranges, with no significant group differences. These findings indicate no evidence of cardiac dysfunction or increased risk. However, the modest increases in HR and SBP warrant attention due to potential cardiovascular implications. Based on our findings and prior research, we conclude that long-term use of long-acting methylphenidate appears cardiovascularly safe in late adolescence and early adulthood.</p> <ref id="AN0182791760-13"> <title> References </title> <blist> <bibl id="bib1" idref="ref12" type="bt">1</bibl> <bibtext> Al Saikhan L., Park C., Hardy R., Hughes A. (2019). Prognostic implications of left ventricular strain by speckle-tracking echocardiography in the general population: A meta-analysis. Vascular Health and Risk Management, 15, 229–251. https://doi.org/10.2147/VHRM.S206747</bibtext> </blist> <blist> <bibl id="bib2" idref="ref1" type="bt">2</bibl> <bibtext> Ayano G., Tsegay L., Gizachew Y., Necho M., Yohannes K., Abraha M., Demelash S., Anbesaw T., Alati R. (2023). Prevalence of attention deficit hyperactivity disorder in adults: Umbrella review of evidence generated across the globe. Psychiatry Research, 328, Article 115449. https://doi.org/10.1016/j.psychres.2023.115449</bibtext> </blist> <blist> <bibl id="bib3" idref="ref8" type="bt">3</bibl> <bibtext> Borovac J. A., D'Amario D., Bozic J., Glavas D. (2020). Sympathetic nervous system activation and heart failure: Current state of evidence and the pathophysiology in the light of novel biomarkers. World Journal of Cardiology, 12(8), 373–408. https://doi.org/10.4330/wjc.v12.i8.373</bibtext> </blist> <blist> <bibl id="bib4" idref="ref30" type="bt">4</bibl> <bibtext> Cooper W. O., Habel L. A., Sox C. M., Chan K. A., Arbogast P. G., Cheetham T. C., Murray K. T., Quinn V. P., Stein C. M., Callahan S. T., Fireman B. H., Fish F. A., Kirshner H. S., O'Duffy A., Connell F. A., Ray W. A. (2011). ADHD drugs and serious cardiovascular events in children and young adults. The New England Journal of Medicine, 365(20), 1896–1904. https://doi.org/10.1056/NEJMoa1110212</bibtext> </blist> <blist> <bibl id="bib5" idref="ref3" type="bt">5</bibl> <bibtext> Cortese S., Adamo N., Del Giovane C., Mohr-Jensen C., Hayes A. J., Carucci S., Atkinson L. Z., Tessari L., Banaschewski T., Coghill D., Hollis C., Simonoff E., Zuddas A., Barbui C., Purgato M., Steinhausen H. C., Shokraneh F., Xia J., Cipriani A. (2018). Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: A systematic review and network meta-analysis. Lancet Psychiatry, 5(9), 727–738. https://doi.org/10.1016/S2215-0366(18)30269-4</bibtext> </blist> <blist> <bibl id="bib6" idref="ref10" type="bt">6</bibl> <bibtext> Curtis B. M., O'Keefe J. H. Jr. (2002). Autonomic tone as a cardiovascular risk factor: The dangers of chronic fight or flight. Mayo Clinic Proceedings, 77(1), 45–54. https://doi.org/10.4065/77.1.45</bibtext> </blist> <blist> <bibl id="bib7" idref="ref7" type="bt">7</bibl> <bibtext> Danielson M. L., Bitsko R. H., Ghandour R. M., Holbrook J. R., Kogan M. D., Blumberg S. J. (2018). Prevalence of parent-reported ADHD diagnosis and associated treatment among U.S. children and adolescents, 2016. Journal of Clinical Child & Adolescent Psychology, 47(2), 199–212. https://doi.org/10.1080/15374416.2017.1417860</bibtext> </blist> <blist> <bibl id="bib8" idref="ref11" type="bt">8</bibl> <bibtext> Grassi G., Seravalle G., Mancia G. (2015). Sympathetic activation in cardiovascular disease: Evidence, clinical impact and therapeutic implications. European Journal of Clinical Investigation, 45(12), 1367-1375. https://doi.org/10.1111/eci.12553</bibtext> </blist> <blist> <bibl id="bib9" idref="ref9" type="bt">9</bibl> <bibtext> He X., Zhao M., Bi X., Sun L., Yu X., Zhao M., Zang W. (2015). Novel strategies and underlying protective mechanisms of modulation of vagal activity in cardiovascular diseases. British Journal of Pharmacology, 172(23), 5489–5500. https://doi.org/10.1111/bph.13010</bibtext> </blist> <blist> <bibtext> Jee S. H., Sull J. W., Park J., Lee S. Y., Ohrr H., Guallar E., Samet J. M. (2006). Body-mass index and mortality in Korean men and women. The New England Journal of Medicine, 355(8), 779–787. https://doi.org/10.1056/NEJMoa054017</bibtext> </blist> <blist> <bibtext> Kalam K., Otahal P., Marwick T. H. (2014). Prognostic implications of global LV dysfunction: A systematic review and meta-analysis of global longitudinal strain and ejection fraction. Heart, 100(21), 1673–1680. https://doi.org/10.1136/heartjnl-2014-305538</bibtext> </blist> <blist> <bibtext> Kara T., Mutlu Mihcioglu A., Yilmaz S., Akaltun I. (2018). Effects of long-term use of prescription methylphenidate on myocardial performance in children with attention-deficit/hyperactivity disorder: A tissue doppler imaging study. Journal of Child and Adolescent Psychopharmacology. Advance online publication. https://doi.org/10.1089/cap.2018.0052</bibtext> </blist> <blist> <bibtext> Lang R. M., Badano L. P., Mor-Avi V., Afilalo J., Armstrong A., Ernande L., Flachskampf F. A., Foster E., Goldstein S. A., Kuznetsova T., Lancellotti P., Muraru D., Picard M. H., Rietzschel E. R., Rudski L., Spencer K. T., Tsang W., Voigt J. U. (2015). Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. European Heart Journal - Cardiovascular Imaging, 16(3), 233–270. https://doi.org/10.1093/ehjci/jev014</bibtext> </blist> <blist> <bibtext> Lang R. M., Carroll J. D., Nakamura S., Itoh H., Rajfer S. I. (1988). Role of adrenoceptors and dopamine receptors in modulating left ventricular diastolic function. Circulation Research, 63(1), 126–134. https://doi.org/10.1161/01.res.63.1.126</bibtext> </blist> <blist> <bibtext> Mick E., McManus D. D., Goldberg R. J. (2013). Meta-analysis of increased heart rate and blood pressure associated with CNS stimulant treatment of ADHD in adults. European Neuropsychopharmacology, 23(6), 534–541. https://doi.org/10.1016/j.euroneuro.2012.06.011</bibtext> </blist> <blist> <bibtext> Nazarova V. A., Sokolov A. V., Chubarev V. N., Tarasov V. V., Schioth H. B. (2022). Treatment of ADHD: Drugs, psychological therapies, devices, complementary and alternative methods as well as the trends in clinical trials. Frontiers in Pharmacology, 13, Article 1066988. https://doi.org/10.3389/fphar.2022.1066988</bibtext> </blist> <blist> <bibtext> Olfson M., Huang C., Gerhard T., Winterstein A. G., Crystal S., Allison P. D., Marcus S. C. (2012). Stimulants and cardiovascular events in youth with attention-deficit/hyperactivity disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 51(2), 147–156. https://doi.org/10.1016/j.jaac.2011.11.008</bibtext> </blist> <blist> <bibtext> Perret-Guillaume C., Joly L., Benetos A. (2009). Heart rate as a risk factor for cardiovascular disease. Progress in Cardiovascular Diseases, 52(1), 6–10. https://doi.org/10.1016/j.pcad.2009.05.003</bibtext> </blist> <blist> <bibtext> Punja S., Shamseer L., Hartling L., Urichuk L., Vandermeer B., Nikles J., Vohra S. (2016). Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database of Systematic Reviews, 2(2), CD009996. https://doi.org/10.1002/14651858.CD009996.pub2</bibtext> </blist> <blist> <bibtext> Rasmussen V. G., Poulsen S. H., Dupont E., Ostergaard K., Safikhany G., Egeblad H. (2008). Ergotamine-derived dopamine agonists and left ventricular function in Parkinson patients: Systolic and diastolic function studied by conventional echocardiography, tissue Doppler imaging, and two-dimensional speckle tracking. European Journal of Echocardiography, 9(6), 803–808. https://doi.org/10.1093/ejechocard/jen160</bibtext> </blist> <blist> <bibtext> Reynolds K., Pietrzak R. H., El-Gabalawy R., Mackenzie C. S., Sareen J. (2015). Prevalence of psychiatric disorders in U.S. older adults: Findings from a nationally representative survey. World Psychiatry, 14(1), 74–81. https://doi.org/10.1002/wps.20193</bibtext> </blist> <blist> <bibtext> Salari N., Ghasemi H., Abdoli N., Rahmani A., Shiri M. H., Hashemian A. H., Akbari H., Mohammadi M. (2023). The global prevalence of ADHD in children and adolescents: A systematic review and meta-analysis. Italian Journal of Pediatrics, 49(1), 48. https://doi.org/10.1186/s13052-023-01456-1</bibtext> </blist> <blist> <bibtext> Schneider H. J., Friedrich N., Klotsche J., Pieper L., Nauck M., John U., Dörr M., Felix S., Lehnert H., Pittrow D., Silber S., Völzke H., Stalla G. K., Wallaschofski H., Wittchen H. U. (2010). The predictive value of different measures of obesity for incident cardiovascular events and mortality. The Journal of Clinical Endocrinology and Metabolism, 95(4), 1777–1785. https://doi.org/10.1210/jc.2009-1584</bibtext> </blist> <blist> <bibtext> Storebo O. J., Storm M. R. O., Pereira Ribeiro J., Skoog M., Groth C., Callesen H. E., Schaug J. P., Darling Rasmussen P., Huus C. L., Zwi M., Kirubakaran R., Simonsen E., Gluud C. (2023). Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). Cochrane Database of Systematic Reviews, 3(3), CD009885. https://doi.org/10.1002/14651858.CD009885.pub3</bibtext> </blist> <blist> <bibtext> Take G., Bahcelioglu M., Oktem H., Tunc E., Gozil R., Erdogan D., Calguner E., Helvacioglu F., Giray S. G., Elmas C. (2008). Dose-dependent immunohistochemical and ultrastructural changes after oral methylphenidate administration in rat heart tissue. Anatomia, Histologia, Embryologia, 37(4), 303–308. https://doi.org/10.1111/j.1439-0264.2008.00845.x</bibtext> </blist> <blist> <bibtext> Westover A. N., Nakonezny P. A., Winhusen T., Adinoff B., Vongpatanasin W. (2013). Risk of methylphenidate-induced prehypertension in normotensive adult smokers with attention deficit hyperactivity disorder. The Journal of Clinical Hypertension, 15(2), 124–132. https://doi.org/10.1111/jch.12039</bibtext> </blist> <blist> <bibtext> Woodward M., Webster R., Murakami Y., Barzi F., Lam T. H., Fang X., Suh I., Batty G. D., Huxley R., & from the Asia Pacific Cohort Studies, Collaboration. (2014). The association between resting heart rate, cardiovascular disease and mortality: Evidence from 112,680 men and women in 12 cohorts. European Journal of Preventive Cardiology, 21(6), 719–726. https://doi.org/10.1177/2047487312452501</bibtext> </blist> <blist> <bibtext> Zhang L. J., Chen K. Q., Shi Y. Y., Qiao X. L., Wang L. Y., Zheng X. Z. (2018). Findings on 3D speckle tracking echocardiography in asymptomatic methamphetamine abusers. The International Journal of Cardiovascular Imaging, 34(10), 1589–1593. https://doi.org/10.1007/s10554-018-1381-6</bibtext> </blist> </ref> <ref id="AN0182791760-14"> <title> Footnotes </title> <blist> <bibtext> The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.</bibtext> </blist> <blist> <bibtext> The author(s) received no financial support for the research, authorship, and/or publication of this article.</bibtext> </blist> <blist> <bibtext> Çağatay Tunca</bibtext> </blist> <blist> <bibtext>Graph</bibtext> </blist> <blist> <bibtext>https://orcid.org/0000-0001-7111-8450 İbrahim Hakan Güllü</bibtext> </blist> <blist> <bibtext>Graph</bibtext> </blist> <blist> <bibtext>https://orcid.org/0000-0003-2579-9755 Saadet Demirtaş İnci</bibtext> </blist> <blist> <bibtext>Graph</bibtext> </blist> <blist> <bibtext>https://orcid.org/0000-0003-2900-2926 Kamuran Kalkan</bibtext> </blist> <blist> <bibtext>Graph</bibtext> </blist> <blist> <bibtext>https://orcid.org/0000-0001-6204-316X Ruken Demirkol Tunca</bibtext> </blist> <blist> <bibtext>Graph</bibtext> </blist> <blist> <bibl id="bib10" idref="ref19" type="bt"></bibl> <bibtext>https://orcid.org/0000-0002-9195-1893 Ayşegül Efe</bibtext> </blist> <blist> <bibl id="bib11" idref="ref13" type="bt"></bibl> <bibtext>Graph</bibtext> </blist> <blist> <bibl id="bib12" idref="ref27" type="bt"></bibl> <bibtext>https://orcid.org/0000-0003-4507-6511 Mehmet Taha Özkan</bibtext> </blist> <blist> <bibl id="bib13" idref="ref16" type="bt"></bibl> <bibtext>Graph</bibtext> </blist> <blist> <bibl id="bib14" idref="ref29" type="bt"></bibl> <bibtext>https://orcid.org/0000-0002-7977-1785 Veysel Ozan Tanik</bibtext> </blist> <blist> <bibl id="bib15" idref="ref22" type="bt"></bibl> <bibtext>Graph</bibtext> </blist> <blist> <bibl id="bib16" idref="ref14" type="bt"></bibl> <bibtext>https://orcid.org/0000-0002-7193-4324 Orçun Ortaköylü</bibtext> </blist> <blist> <bibl id="bib17" idref="ref6" type="bt"></bibl> <bibtext>Graph</bibtext> </blist> <blist> <bibl id="bib18" idref="ref23" type="bt"></bibl> <bibtext>https://orcid.org/0000-0002-3846-0585 Nail Burak Özbeyaz</bibtext> </blist> <blist> <bibl id="bib19" idref="ref4" type="bt"></bibl> <bibtext>Graph https://orcid.org/0000-0002-7132-4286</bibtext> </blist> </ref> <aug> <p>By Çağatay Tunca; İbrahim Hakan Güllü; Saadet Demirtaş İnci; Kamuran Kalkan; Ruken Demirkol Tunca; Ayşegül Efe; Ayşe Nur Özkaya Ibiş; Alperen Taş; Mehmet Taha Özkan; Veysel Ozan Tanik; Orçun Ortaköylü and Nail Burak Özbeyaz</p> <p>Reported by Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author; Author</p> <p></p> <p>Çağatay Tunca is a Cardiologist at Ankara Etlik City Hospital. His clinical and research interests focus on interventional cardiology and heart failure management.</p> <p>İbrahim Hakan Güllü is a Professor of Cardiology at Ankara Etlik City Hospital. He specializes in advanced cardiac imaging techniques and structural heart diseases.</p> <p>Saadet Demirtaş İnci is an Associate Professor of Cardiology at Ankara Etlik City Hospital. She specializes in advanced cardiac imaging techniques and structural heart diseases.</p> <p>Kamuran Kalkan is an Associate Professor of Cardiology at Ankara Etlik City Hospital. He is particularly interested in coronary artery disease and preventive cardiology.</p> <p>Ruken Demirkol Tunca is a Specialist in Child and Adolescent Psychiatry at Ankara Etlik City Hospital. Her expertise includes neurodevelopmental disorders and adolescent mental health.</p> <p>Ayşegül Efe is an Associate Professor in Child and Adolescent Psychiatry at Ankara Etlik City Hospital. Her primary focus is on anxiety disorders and the psychiatric impact of chronic illnesses in children.</p> <p>Ayşe Nur Özkaya Ibiş is a Cardiologist at Ankara Etlik City Hospital. Her areas of interest include valvular heart disease and echocardiography.</p> <p>Alperen Taş is a Cardiologist at Ankara Etlik City Hospital. He focuses on heart rhythm disorders and their interventional treatments.</p> <p>Mehmet Taha Özkan is a Cardiologist at Ankara Etlik City Hospital. His clinical expertise includes heart failure and device therapy.</p> <p>Veysel Ozan Tanik is an Associate Professor of Cardiology at Ankara Etlik City Hospital. His research includes vascular medicine and advanced interventional techniques.</p> <p>Orçun Ortaköylü is a Specialist in Psychiatry at Dışkapı Yıldırım Beyazıt Training and Research Hospital. His interests lie in mood disorders and the integration of mental health services in primary care.</p> <p>Nail Burak Özbeyaz is a Cardiologist at Ankara University Cebeci Hospital. He specializes in interventional cardiology.</p> </aug> <nolink nlid="nl1" bibid="bib22" firstref="ref2"></nolink> <nolink nlid="nl2" bibid="bib24" firstref="ref5"></nolink> <nolink nlid="nl3" bibid="bib21" firstref="ref15"></nolink> <nolink nlid="nl4" bibid="bib28" firstref="ref17"></nolink> <nolink nlid="nl5" bibid="bib20" firstref="ref18"></nolink> <nolink nlid="nl6" bibid="bib23" firstref="ref20"></nolink> <nolink nlid="nl7" bibid="bib26" firstref="ref21"></nolink> <nolink nlid="nl8" bibid="bib27" firstref="ref24"></nolink> <nolink nlid="nl9" bibid="bib25" firstref="ref28"></nolink>
Header DbId: eric
DbLabel: ERIC
An: EJ1467552
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Echocardiographic Evaluation of the Effect of Long-Term Methylphenidate Use on Cardiovascular Functions
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Çagatay+Tunca%22">Çagatay Tunca</searchLink> (ORCID <externalLink term="https://orcid.org/0000-0001-7111-8450">0000-0001-7111-8450</externalLink>)<br /><searchLink fieldCode="AR" term="%22Ibrahim+Hakan+Güllü%22">Ibrahim Hakan Güllü</searchLink> (ORCID <externalLink term="https://orcid.org/0000-0003-2579-9755">0000-0003-2579-9755</externalLink>)<br /><searchLink fieldCode="AR" term="%22Saadet+Demirtas+Inci%22">Saadet Demirtas Inci</searchLink> (ORCID <externalLink term="https://orcid.org/0000-0003-2900-2926">0000-0003-2900-2926</externalLink>)<br /><searchLink fieldCode="AR" term="%22Kamuran+Kalkan%22">Kamuran Kalkan</searchLink> (ORCID <externalLink term="https://orcid.org/0000-0001-6204-316X">0000-0001-6204-316X</externalLink>)<br /><searchLink fieldCode="AR" term="%22Ruken+Demirkol+Tunca%22">Ruken Demirkol Tunca</searchLink> (ORCID <externalLink term="https://orcid.org/0000-0002-9195-1893">0000-0002-9195-1893</externalLink>)<br /><searchLink fieldCode="AR" term="%22Aysegül+Efe%22">Aysegül Efe</searchLink> (ORCID <externalLink term="https://orcid.org/0000-0003-4507-6511">0000-0003-4507-6511</externalLink>)<br /><searchLink fieldCode="AR" term="%22Ayse+Nur+Özkaya+Ibis%22">Ayse Nur Özkaya Ibis</searchLink><br /><searchLink fieldCode="AR" term="%22Alperen+Tas%22">Alperen Tas</searchLink><br /><searchLink fieldCode="AR" term="%22Mehmet+Taha+Özkan%22">Mehmet Taha Özkan</searchLink> (ORCID <externalLink term="https://orcid.org/0000-0002-7977-1785">0000-0002-7977-1785</externalLink>)<br /><searchLink fieldCode="AR" term="%22Veysel+Ozan+Tanik%22">Veysel Ozan Tanik</searchLink> (ORCID <externalLink term="https://orcid.org/0000-0002-7193-4324">0000-0002-7193-4324</externalLink>)<br /><searchLink fieldCode="AR" term="%22Orçun+Ortaköylü%22">Orçun Ortaköylü</searchLink> (ORCID <externalLink term="https://orcid.org/0000-0002-3846-0585">0000-0002-3846-0585</externalLink>)<br /><searchLink fieldCode="AR" term="%22Nail+Burak+Özbeyaz%22">Nail Burak Özbeyaz</searchLink> (ORCID <externalLink term="https://orcid.org/0000-0002-7132-4286">0000-0002-7132-4286</externalLink>)
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="SO" term="%22Journal+of+Attention+Disorders%22"><i>Journal of Attention Disorders</i></searchLink>. 2025 29(5):326-335.
– Name: Avail
  Label: Availability
  Group: Avail
  Data: SAGE Publications. 2455 Teller Road, Thousand Oaks, CA 91320. Tel: 800-818-7243; Tel: 805-499-9774; Fax: 800-583-2665; e-mail: journals@sagepub.com; Web site: https://sagepub.com
– Name: PeerReviewed
  Label: Peer Reviewed
  Group: SrcInfo
  Data: Y
– Name: Pages
  Label: Page Count
  Group: Src
  Data: 10
– Name: DatePubCY
  Label: Publication Date
  Group: Date
  Data: 2025
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: Journal Articles<br />Reports - Research
– Name: Subject
  Label: Descriptors
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Late+Adolescents%22">Late Adolescents</searchLink><br /><searchLink fieldCode="DE" term="%22Young+Adults%22">Young Adults</searchLink><br /><searchLink fieldCode="DE" term="%22Attention+Deficit+Hyperactivity+Disorder%22">Attention Deficit Hyperactivity Disorder</searchLink><br /><searchLink fieldCode="DE" term="%22Heart+Disorders%22">Heart Disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Metabolism%22">Metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+Use%22">Drug Use</searchLink><br /><searchLink fieldCode="DE" term="%22Outcomes+of+Treatment%22">Outcomes of Treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Pharmacology%22">Pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22Causal+Models%22">Causal Models</searchLink><br /><searchLink fieldCode="DE" term="%22Test+Results%22">Test Results</searchLink>
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1177/10870547241307680
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 1087-0547<br />1557-1246
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Objective: ADHD is one of the most common neurodevelopmental disorders, seen in children and adolescents, and is often treated with various pharmacological agents, especially methylphenidate. There are differing opinions in the literature regarding the cardiovascular safety of long-term methylphenidate use. Studies suggest that the drug may increase the risk of hypertension, myocardial infarction, ventricular arrhythmia, sudden cardiac death, cardiomyopathy, heart failure (HF), pulmonary hypertension, and stroke. This study aimed to compare the clinical and echocardiographic characteristics of patients diagnosed with ADHD who have been using long-acting methylphenidate for an extended period with age-gender matched healthy volunteers. Materials and Methods: A total of 70 patients diagnosed with ADHD, who had been using long-acting methylphenidate for 2 years or more, and 51 healthy volunteers, who were referred to our clinic, were included in our study. Patients were evaluated with basic and advanced techniques such as Motion Mode (M-mode), two-dimensional (2D), Doppler, and 2D-Speckle Tracking (STE) using transthoracic echocardiography. All other data were evaluated instantly after the processing with the strain images analysis program. Results: Statistically significant differences were observed between the case and control groups in terms of body mass index (BMI) and systolic blood pressure (SBP), with BMI negatively correlated and SBP positively correlated with methylphenidate use duration. There was no significant difference between the groups in apical four-chamber, three-chamber, two-chamber, and global longitudinal strain (GLS) values obtained by 2D-STE technique indicating early deterioration. The Left Ventricular (LV) lateral E' value, which indicates diastolic dysfunction, was lower in the drug group, but still within normal limits. The lateral LV E', Right Ventricular (RV) E', and RV A' values showed a significant negative correlation with the duration of drug use and remained within normal limits. Other parameters evaluating systolic/diastolic function such as E/E', left ventricular ejection fraction (LVEF), myocardial performance index (MPI), and tricuspid/mitral annular plane systolic excursion (TAPSE/MAPSE) did not differ significantly between the groups and were within normal limits. Valve structures and regurgitations were also not significantly different between the two groups. Conclusion: Considering all parameters, we conclude that long-term use of long-acting methylphenidate does not cause cardiovascular dysfunction in late adolescent and early adult individuals. The observed differences in the E' lateral value between the case and control groups, as well as the slight correlation of lateral LV E', RV E', and RV A' values with the duration of use, do not directly indicate cardiac dysfunction.
– Name: AbstractInfo
  Label: Abstractor
  Group: Ab
  Data: As Provided
– Name: DateEntry
  Label: Entry Date
  Group: Date
  Data: 2025
– Name: AN
  Label: Accession Number
  Group: ID
  Data: EJ1467552
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=eric&AN=EJ1467552
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1177/10870547241307680
    Languages:
      – Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 10
        StartPage: 326
    Subjects:
      – SubjectFull: Late Adolescents
        Type: general
      – SubjectFull: Young Adults
        Type: general
      – SubjectFull: Attention Deficit Hyperactivity Disorder
        Type: general
      – SubjectFull: Heart Disorders
        Type: general
      – SubjectFull: Metabolism
        Type: general
      – SubjectFull: Drug Use
        Type: general
      – SubjectFull: Outcomes of Treatment
        Type: general
      – SubjectFull: Pharmacology
        Type: general
      – SubjectFull: Causal Models
        Type: general
      – SubjectFull: Test Results
        Type: general
    Titles:
      – TitleFull: Echocardiographic Evaluation of the Effect of Long-Term Methylphenidate Use on Cardiovascular Functions
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Çagatay Tunca
      – PersonEntity:
          Name:
            NameFull: Ibrahim Hakan Güllü
      – PersonEntity:
          Name:
            NameFull: Saadet Demirtas Inci
      – PersonEntity:
          Name:
            NameFull: Kamuran Kalkan
      – PersonEntity:
          Name:
            NameFull: Ruken Demirkol Tunca
      – PersonEntity:
          Name:
            NameFull: Aysegül Efe
      – PersonEntity:
          Name:
            NameFull: Ayse Nur Özkaya Ibis
      – PersonEntity:
          Name:
            NameFull: Alperen Tas
      – PersonEntity:
          Name:
            NameFull: Mehmet Taha Özkan
      – PersonEntity:
          Name:
            NameFull: Veysel Ozan Tanik
      – PersonEntity:
          Name:
            NameFull: Orçun Ortaköylü
      – PersonEntity:
          Name:
            NameFull: Nail Burak Özbeyaz
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 03
              Type: published
              Y: 2025
          Identifiers:
            – Type: issn-print
              Value: 1087-0547
            – Type: issn-electronic
              Value: 1557-1246
          Numbering:
            – Type: volume
              Value: 29
            – Type: issue
              Value: 5
          Titles:
            – TitleFull: Journal of Attention Disorders
              Type: main
ResultId 1