Attention deficit/hyperactivity disorder (ADHD) is a common neuropsychiatric disorder for which medication plays a pivotal role for clinical management. |
Amphetamine and atomoxetine were associated with small but statistically significant pre–post increases in systolic and diastolic blood pressure and heart rate in children and adolescents with ADHD, while methylphenidate treatment had this effect only on systolic blood pressure in these individuals. |
Of the participants on medication, 12.6% reported other cardiovascular effects and 2% discontinued their medication treatment due to any cardiovascular effect; other cardiovascular effects resolved spontaneously, medication doses were changed or the effects were not considered clinically relevant. There were no significant differences in terms of the severity of cardiovascular effects between the medication treatments. |
More research into the long-term effects on the left ventricular mass of these relatively small changes of blood pressure and heart rate associated with ADHD medication treatment is required. |
1 Introduction
2 Methods
2.1 Objectives and Inclusion Criteria
2.2 Search Strategy
2.3 Outcome Measures
2.4 Study Selection
2.5 Data Extraction
2.6 Statistical Analyses
3 Results
Study | Type of medication | Study design | Sample size, N (drop-out %) | Mean age, y (range) | Male, % | Type of comparison | Doses, mean [SD] or range per day | Length of study/observation, weeks |
---|---|---|---|---|---|---|---|---|
MPH | ||||||||
Buitelaar et al. [31] | MPH | Prospective, double-blind placebo-controlled study | 46 (NR) | 9.3 (7–13) | 88 | Pindolol and placebo | 20 mg | 4 |
Hammerness et al. [48] | OROS-MPH | Open-label study | 114 (50) | 14.1 (12–18) | 73 | NR | 0.5–1.75 mg/kg | 24 |
Kim et al. [30] | OROS-MPH | Prospective, open-label, flexible-dose | 24 (11.1) | 8.2 (6–12) | 92 | NR | 18–45 mg | 24 |
Lee et al. [33] | OROS-MPH | Open-label study | 47 (14.5) | 14.3 (12–18) | 78 | NR | 18–72 mg | 12 |
Wilens et al. [34] | OROS-MPH | Open-label study | 432 (29) | NR (6–13) | NR | NR | 18–54 mg | 48 |
Zeiner [35] | MPH | Open-label study | 23 (13) | 9.3 (7–12) | 100 | No medication | 0.55 mg/kg | 84 |
AMP | ||||||||
Coghill et al. [36] | LDX | Open-label trial | 276 (39.9) | 10.9 (6–17) | 76.8 | Placebo | 30–70 mg | 52 |
Donner et al. [37] | MAS XR | Prospective, open-label, no comparative, community-based study | 2968 (1.2) | 9.5 (6–13) | 76.1 | Doses | 10–40 mg | 14 |
Findling et al. [38] | LDX | Open-label, multicentre, randomised, double-blind, placebo-controlled study | 314 (42) | 14.5 (13–17) | 70.6 | Placebo (no data) | 30–70 mg | 52 |
Wilens et al. [39]b
| MAS XR | Open-label study | 138 (NR) | 14.4 | 71.0 | NR | 10–40 mg | 16 |
ATX | ||||||||
Fuentes et al. [40] | ATX | Randomised, controlled, open-label study | 199 (21.1) | 9.2 (6–16) | 79.4 | Any other pharmacological ADHD treatment | 0.5–1.8 mg/kg | 48 |
Ghuman et al. [41] | ATX | Open-label pilot study | 12 (0) | 5.0 (3.5–5.8) | 75 | NR | Up titration 18–40 mg | 6 |
Hammerness et al. [42] | ATX | Two-phase open study | 72 (16.7) | 9.3 (6–17) | 76 | ATX (vs ATX and OROS-MPH) | ATX 0.5–1.4 mg/kg OROS-MPH 18/54 mg | 4 |
>1 medication | ||||||||
Arcieri et al. [43] | MPH ATX | Open-label, prospective, observational study | 351 (82.6) | 10.4 (6–18) | 87 | MPH and BTa
| MPH 18.4 (10.4) | 96 |
350 (89.1) | 10.8 (6–18) | 90 | ATX and BT | ATX 38.6 (20.5) | ||||
Dittmann et al. [47] | LDX ATX | Head-to-head, randomised, double-blind, active-controlled study | 128 (24.8) | 10.9 (3.01) | 75.2 | LDX | LDX 30–70 mg ATX <70 kg: 0.5–1.4 mg/kg; >70 kg: 40–100 mg | 9 |
134 (24.6) | 10.4 (2.84) | 76.9 | ATX | |||||
Kratochvil et al. [44] | MPH ATX | A prospective, randomised, open-label | 40 (37.5) | 10.4 (7–15) | 100 | MPH | 5–60 mg | 10 |
180 (35.9) | 10.4 (7–15) | 90.8 | ATX | 0.2–1.0 mg/kg | 10 | |||
Sangal et al. [45] | MPH ATX | Randomised, double-blind crossover | 83 (5.3) | 10.1 (6–14) | 75 | MPH | 0.45–1.8 mg/kg | 7 |
81 (NR) | NR | NR | ATX | NR | 7 | |||
Yildiz et al. [46]b
| OROS-MPH ATX | Open-label study | 11 (13.3) | 9.0 (8–13) | 82 | OROS-MPH | 18–54 mg | 12 |
14 (17.6) | 9.78 (8–12) | 93 | ATX | 18–60 mg | 12 |
3.1 Diastolic Blood Pressure
3.2 Systolic Blood Pressure
3.3 Heart Rate
3.4 Multiple Measurements Over Time
3.5 Moderators of the Treatment Effect
3.6 Cardiovascular Adverse Effects on Individual Level
Study | Hypertension and heart rate >90th percentile | Tachycardia | Brachycardia | Other cardiovascular effects | ECG abnormalities | Discontinued treatment due to cardiovascular effect/moment of discontinuation |
---|---|---|---|---|---|---|
MPH | ||||||
Arcieri et al. [43] | NR | 6/351 (1.7%) | 10/351 (2.8%) | 1/351 (0.3%) arrhythmia | 4.7% (6 mo), 10% (12 mo), 10.4% (24 mo) 5/351 (1.7%) lengthened QTc | 1(Altered ECG, arrhythmia)/after 6 mo |
Buitelaar et al. [31] | NR | NR | NR | NR | No ECG | 0 |
Hammerness et al. [32] | 6% (n = 7; probably because of high BMI) | 0 | 0 | 0 | 0% | 1 (recurrent palpitations)/after first 6 wk |
Kim et al. [30] | 0 | 0 | 0 | 0 | 0% | 0 |
Kratochvil et al. [44] | NR | 2/40 (5%) | NR | 0 | 0% | NR if was due to cardiovascular event |
Lee et al. [33] | NR | NR | NR | 0 | No ECG | 0 |
Sangal et al. [55] | NR | NR | NR | 0 | 0% | 0 |
Wilens et al. [34] | 1 SBP >130 mmHg | 0% | 0% | 0% | 0% | 1 (SBP >130 mmHg at 2 min occasions)/NR |
Yildiz et al. [46] | NR | NR | NR | 0 | 0% | 2/NR |
Zeiner [35] | NR | NR | NR | NR | No ECG | NR |
AMP | ||||||
Coghill et al. [56] | NR | NR | NR | NR | No ECG | 0 |
Dittmann et al. [47] | 11/94 (11.7%) DBP >80 mmHg 12/94 (12.8%) >SBP 120 mmHg 4/127 (3.1%) HR <50 bpm 19/127 (15.0%) HR >100 bpm | NR | NR | NR | 8/83 (9.6%) HR >100 bpm QTcF interval change from screening >30 ms or <6 ms = 2/83 (2.4%) | 0 |
Donner et al. [37] | 2.5% SBP or DBP values that were >95th percentile 3.6% had an HR increase >25–110 bpm 6 DBP >90 mmHg 22 SBP >130 mmHg 30 HR >120 bpm 0 HR <50 bpm | 2 (0.1%) | NR | 7/2968 (0.2%) including hypertension, palpitations, and tachycardia (no numbers of events separately) | 63 (2.1%) | 9 cardiovascular events, including hypertension, palpitations, and tachycardia (no numbers of effect separately), 1 right bundle branch block, 1 prolonged QT interval/NR |
Findling et al. [38] | 33/265 (12.5%) SBP >120 mmHg + increase of 10 mmHg 4/265 (1.5%) SBP >140 mmHg 20/265 (7.5%) DBP >80–90 mmHg with increase of 10 mmHg 11/265 (4.2%) HR >100–120 bpm, or increase of 15 bpm | NR | NR | NR | 12/257 (4.7%) ECG HR >100 bpm | 0 |
Wilens et al. [57] | 21 increase of DBP >10 mmHg 5 increase SBP >20 mmHg 1 HR 110–115 bpm 6 pulse change of >25 bpm | 1 | NR | NR | 34/138 at baseline 24/138 at end point | 0 |
ATX | ||||||
Arcieri et al. [43] | NR | 6/350 (1.7%) | 1/350 (0.3%) | 1/350 (0.3%) arrhythmia | After 6 mo: 8 (3.6%) After 12 mo: 7 (4.1%) After 24 mo: 0 1/350 (0.3%) a lengthened QTc | 1 (arrhythmia)/after 6 mo |
Dittmann et al. [47] | Children: 13/98 (13.3%) DBP >80 mmHg 11/98 (11.2%) SBP >120 mmHg 32/132 (24.2%) HR >100 bpm Adolescents: 6/34 (17.6%) DBP >80 mmHg 3/34 (8.8%) SBP >130 mmHg 16/34 (47.1%) >SBP 120 mmHg | NR | NR | NR | 8/91 (1.1%) HR >100 bpm QTcF interval change >30 ms or <60 ms = 1/90 (1.1%) | 0 |
Fuentes et al. [40] | NR | NR | NR | NR | NR | 0 |
Ghuman et al. [41] | NR | NR | NR | 0 | 0% | 0 |
Hammerness et al. [42] | 1 HR >120 bpm | NR | NR | NR | 0% | 0 |
Kratochvil et al. [44] | NR | 11/184 (6%) | NR | 0 | 0% | 0 |
Sangal et al. [55] | NR | NR | NR | NR | 0% | 0 |
Yildiz et al. [46] | NR | NR | NR | NR | 0% | 0 |