Heart rate variability and methylphenidate in children with ADHD

Abstract

Although an extensive number of studies support the efficacy and tolerability of stimulants in the treatment of attention deficit/hyperactivity disorder (ADHD), in recent years, increasing concerns have been raised about their cardiovascular safety. We investigated whether a time domain analysis of heart rate variability (HRV) recordings in 24-h ECG under medication with stimulants yielded new information about therapy control in ADHD. We analysed the HRV parameter standard deviation of all normal sinus RR intervals over 24 h (SDNN), percentage of successive normal sinus RR intervals > 50 ms (pNN50) and root-mean-square of the successive normal sinus RR interval difference (rMSSD) from 23 children diagnosed by ADHD (19 boys and 4 girls), aged 10.5 ± 2.2 years, who were consecutively referred to our outpatient clinic for paediatric cardiology. Eleven children received medication with methylphenidate (MPH), while twelve children were initially examined without medication. Of these, eight probands were re-examined after therapy with MPH was established. Controls comprised 19 children (10 boys, 9 girls) from our Holter ECG data base without any cardiac or circulatory disease. Compared to healthy controls, the ADHD children with and without MPH treatment showed significantly higher mean heart rates (ADHD without MPH: 94.3 ± 2.2; ADHD with MPH: 90.5 ± 1.8, controls: 84.7 ± 1.8). pNN50 (ADHD without MPH: 6.5 ± 2.7; ADHD with MPH: 14.2 ± 6.9, controls: 21.5 ± 9.0) and rMSSD (ADHD without MPH: 26.1 ± 4.1; ADHD with MPH: 36.7 ± 8.3, controls: 44.5 ± 10.1) were lowest in ADHD children without MPH, middle in ADHD children with MPH and highest in controls. SDNN values were not significantly different. The hourly analysis shows highly significant reduced pNN50 and rMSSD values in untreated ADHD children between 5:00 pm and 6:00 am while the pattern approaches to levels of controls during MPH treatment. Data of this pilot study indicate a decreased vagal tone with significantly diminished HRV and higher heart rates in unmedicated ADHD children. These parameters of autonomic activation are ameliorated by MPH treatment. No evidence for negative impact of MPH on HRV was detected. Further studies will clarify a potential cardio-protective effect of MPH in ADHD.

Cardiovascular Safety of Stimulants in Children with Attention-Deficit/Hyperactivity Disorder: A Nationwide Prospective Cohort Study

“…Animal studies have found that stimulants prolong action potential duration and resting membrane potential in sinoatrial cells (Aileru and Carpentier 1996), affect action-potential repolarization in ventricular myocytes (Casis et al 2000), affect cell membranes in the myocardium (Henderson and Fischer 1995), and have dose-related structural effects on capillary endothelial cells (Bahcelioglu et al 2009). Drug-näive children with ADHD have higher heart rates than controls (Huang and Tsai 2011;Imeraj et al 2011;Buchhorn et al 2012a) and reduced heart rate variability (HRV), which is normalized by methylphenidate (Buchhorn et al 2012b).…”

Heart Rate Variability in Children with Attention-Deficit/Hyperactivity Disorder: A Pilot Study

“…Some studies have assessed HRV in ADHD and have shown that there is autonomic dysregulation. Studies carried out by Shibagaki and Furuya [19] , Beauchaine et al [20] , Buchhorn et al [21,22] and Musser et al [23] showed decreased vagal tone in ADHD. However, studies carried out by Börger et al [24] , Crowell et al [25] , Negrao et al [26] and Wang et al [27] show that there is parasympathetic overarousal in ADHD.…”

Assessment of Cardiovascular Risks due to Methylphenidate in Six Months of Treatment in Children with Attention Deficit and Hyperactivity Disorder

“…Because of its serious side effects and possible sudden death, the F DA i s s u e d a bl a c k b o x w a r n i n g f o r methylphenidate in 2006. To minimize these side effects, a thorough cardiovascular examination should be performed and a detailed family history for cardiovascular events, including any history of sudden death, should be obtained 10 . In this study, none of the patients' relatives had any history of serious cardiovascular diseases.…”