According to the FDA-approved prescribing information for hydrochlorothiazide (HCTZ), hypotension and orthostatic hypotension (OH) are listed as potential cardiovascular adverse reactions that may be aggravated by alcohol, barbiturates, opiates, or other antihypertensive drugs.1 Orthostatic hypotension is defined by the American Autonomic Society and the American Academy of Neurology as at least a 20 mm Hg decrease in systolic blood pressure or a 10 mm Hg decrease in diastolic blood pressure within three minutes of standing.2
Multiple randomized double blind studies evaluating the efficacy and tolerability of HCTZ found few or no reports of hypotension.3-6 One study of 151 patients with mild to moderate hypertension being treated with 25 mg of HCTZ found that side effects potentially caused by hypotension decreased over the 16-week study period (12.6% incidence of dizziness at baseline vs 11.2% at 16 weeks). Eight patients (5.3%) discontinued use due to unspecified adverse effects.3 Another study examining 215 hypertensive patients being treated with 12.5 mg of HCTZ found that only three patients (1.4%) chose to stop treatment due to unspecified adverse events.4 A study of 1,292 hypertensive men (mean age 59±10 years; 48% black) found no side effects occurred more frequently in patients taking HCTZ than placebo.5 A 2011 16-week trial evaluating the safety and efficacy of HCTZ (12.5mg/day; n=128) in hypertensive, elderly (≥70 years) patients found that only one patient (0.8%) had measured hypotension.7
Although hypotension is often not reported as an adverse effect of HCTZ, antihypertensive medications that induce diuresis or impair autonomic reflex mechanisms, including thiazide diuretics like HCTZ, are associated with OH.8 OH symptoms may include transient light-headedness, dizziness, weakness, fatigue, cognitive impairment, nausea, palpitations, and tremulousness. Various factors such as gender, age, food intake, time of day, and state of hydration can affect whether a patient experiences OH. Changes in drug pharmacodynamics and pharmacokinetics occur with age and affect how drugs are metabolized in the body, leading to increased incidence of OH with age.2 Patients experiencing OH are recommended to change their positions slowly and maintain adequate fluid intake of 2.0 to 2.5 L per day.
A cross-sectional analysis of adults ≥75 years old (n=781) found that the total prevalence of OH in patients on at least one antihypertensive was 34%.9 Although the total number of regularly used medicines was associated with the prevalence of OH, no association between OH and particular antihypertensive or causative medicine was found, including diuretics. A different study assessed the prevalence of OH in 994 adults >80 years old (mean age 88±5 years) who were on a variety of antihypertensives and found OH in 18% of the participants.10 The study found that taking thiazide diuretics was not associated with a higher prevalence of experiencing OH. Only beta blockers were significantly associated with a higher occurrence of OH.
References
- Hydrochlorothiazide [package insert]. Morgantown, WV: Mylan Pharmaceuticals, Inc.; 2011.
- Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. Apr 2011;21(2):69-72. doi:10.1007/s10286-011-0119-5
- Helgeland A, Strommen R, Hagelund CH, Tretli S. Enalapril, atenolol, and hydrochlorothiazide in mild to moderate hypertension. A comparative multicentre study in general practice in Norway. Lancet (London, England). Apr 19 1986;1(8486):872-5.
- Philipp T, Anlauf M, Distler A, Holzgreve H, Michaelis J, Wellek S. Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study. HANE Trial Research Group. BMJ (Clinical research ed). Jul 19 1997;315(7101):154-9.
- Materson BJ, Reda DJ, Cushman WC, et al. Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. N Engl J Med. 1993;328(13):914-921. doi:10.1056/nejm199304013281303
- Pareek AK, Messerli FH, Chandurkar NB, et al. Efficacy of Low-Dose Chlorthalidone and Hydrochlorothiazide as Assessed by 24-h Ambulatory Blood Pressure Monitoring. J Am Coll Cardiol. Feb 2 2016;67(4):379-389. doi:10.1016/j.jacc.2015.10.083
- Izzo JL, Jr., Weintraub HS, Duprez DA, et al. Treating systolic hypertension in the very elderly with valsartan-hydrochlorothiazide vs. either monotherapy: ValVET primary results. Journal of clinical hypertension (Greenwich, Conn). Oct 2011;13(10):722-30. doi:10.1111/j.1751-7176.2011.00498.x
- Verwoert GC, Mattace-Raso FU, Hofman A, et al. Orthostatic hypotension and risk of cardiovascular disease in elderly people: the Rotterdam study. J Am Geriatr Soc. Oct 2008;56(10):1816-20. doi:10.1111/j.1532-5415.2008.01946.x
- Hiitola P, Enlund H, Kettunen R, Sulkava R, Hartikainen S. Postural changes in blood pressure and the prevalence of orthostatic hypotension among home-dwelling elderly aged 75 years or older. Journal of human hypertension. Jan 2009;23(1):33-9. doi:10.1038/jhh.2008.81
- Valbusa F, Labat C, Salvi P, Vivian ME, Hanon O, Benetos A. Orthostatic hypotension in very old individuals living in nursing homes: the PARTAGE study. Journal of hypertension. Jan 2012;30(1):53-60. doi:10.1097/HJH.0b013e32834d3d73
.png)
