Risk of methylphenidate-induced prehypertension in normotensive adult smokers with attention deficit hyperactivity disorder

Abstract

The authors studied predictors of methylphenidate-induced increases in blood pressure (BP). In this secondary analysis of a randomized, double-blind, placebo-controlled smoking cessation trial, nonhypertensive adult smokers with attention deficit hyperactivity disorder randomized to osmotic-release oral system methylphenidate (OROS-MPH) (n=115) were matched one-to-one on baseline systolic BP (SBP) (±5 mm Hg) with participants randomized to placebo (n=115) and followed for 10 weeks. In adjusted mixed linear models of SBP and diastolic BP (DBP), baseline normal SBP (P<.0001) and DBP (P<.0001) were associated with significant OROS-MPH-induced increases compared with placebo, whereas significant increases were not observed in participants with baseline prehypertensive SBP (P=.27) and DBP (P=.79). Participants randomized to OROS-MPH with baseline normal BP had increased odds of developing either systolic (odds ratio [OR], 3.32; 95% confidence interval [CI], 1.41-8.37; P=.006) or diastolic prehypertension (OR, 4.32; 95% CI, 1.56-14.0; P=.004) compared with placebo using simple logistic regression. The authors demonstrated an augmented OROS-MPH-induced BP elevation and risk of prehypertension in adults with baseline normal BP. Significantly increased BP was not observed in adults with baseline prehypertension.

Trial registration: ClinicalTrials.gov NCT00253747.

© 2012 Wiley Periodicals, Inc.

Figures

Figure 1

Adjusted least‐squares (LS) means of systolic and diastolic blood pressure among all participants and by baseline blood pressure category (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure [JNC 7]). These graphs, plotted with weekly adjusted LS mean estimates, are a representation of the covariate‐adjusted mixed model results for systolic blood pressure (SBP) and diastolic blood pressure (DBP) presented in Table II. The overall treatment main effect of OROS‐MPH on SBP (A) was F=12.8 (P=.0004), and on DBP (B) was F=6.69 (P=.010). The treatment×blood pressure category interaction effect for SBP (C, E) was F=3.47 (P=.063), and for DBP (D, F) was F=4.35 (P=.038). The treatment×time interaction effect for SBP (A) was F=0.94 (P=.49), and for DBP (B) was F=0.72 (P=.68). The treatment×blood pressure category×time interaction effect for SBP (C, E) was F=0.84 (P=.57), and for DBP (D, F) was F=0.68 (P=.71). *LS mean estimates start in week 2, the first measurement of blood pressure after baseline measurement and randomization. LS mean estimates adjusted for baseline demographics and covariates (see Table II).

Figure 2

Lower baseline blood pressure is associated with greater average weekly osmotic‐release oral system methylphenidate (OROS‐MPH)–induced increase in estimates of blood pressure compared with placebo within tertile categorizations. *Tertile categorizations for baseline blood pressure: systolic blood pressure (SBP) were (1) low (≤110 mm Hg), (2) middle (111–122 mm Hg), and (3) high (123–139 mm Hg); diastolic blood pressure (DBP) were (1) low (≤69 mm Hg), (2) middle (70–77 mm Hg), and (3) high (78–89 mm Hg). †Average of the weekly difference between OROS‐MPH– and placebo‐treated groups during weeks 2 to 10 within tertile categorizations. P values indicate the significance between OROS‐MPH and placebo treatment within tertile categorizations.