DefinePK

Abstract

Objective: This RCT explores the potential pharmacokinetic interactions between commonly prescribed antidepressants and antihypertensive drugs. The study will evaluate how co-administration of these medications may affect drug metabolism, bioavailability, and therapeutic efficacy. The research aims to identify any adverse effects or altered pharmacodynamics that could impact patient care, especially in individuals with comorbid depression and hypertension.
Methods: Participants with controlled hypertension were randomly assigned to various antidepressant classes—SSRIs, SNRIs, tricyclics, norepinephrine–dopamine reuptake inhibitors, tetracyclics, or MAO inhibitors—while continuing standard antihypertensive therapy such as beta-blockers, calcium-channel blockers, ACE inhibitors, ARBs, and thiazide diuretics. Plasma concentration–time data were collected to derive pharmacokinetic parameters, and blood pressure, heart rate, and relevant laboratory measures were tracked to evaluate pharmacodynamic effects and monitor adverse events.Results: CYP2D6-inhibiting antidepressants, such as paroxetine, fluoxetine, and bupropion, significantly elevated metoprolol exposure, leading to more frequent bradycardia. SSRIs combined with thiazides produced a higher rate of hyponatremia, while amitriptyline attenuated the antihypertensive effect of clonidine. Interactions involving ACE inhibitors and ARBs were clinically negligible. Venlafaxine modestly increased systolic blood pressure, whereas fluvoxamine enhanced amlodipine concentrations without hemodynamic consequence.
Conclusion: The study demonstrated that several antidepressants could meaningfully influence the pharmacokinetics and efficacy of antihypertensive drugs. Careful drug selection—favoring agents such as sertraline or escitalopram in hypertensive patients—may optimize therapeutic outcomes and minimize adverse cardiovascular or metabolic events.