Higher levodopa doses tied to blood pressure drop in older adults

Low blood pressure during peak therapy periods in early and midstage patients

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Higher levodopa doses were associated with a drop in blood pressure among older Parkinson’s patients, those with 65 or more years, in the early and middle stages of the disease, a study reported.

Cognitive impairment was identified as a risk factor for a sudden blood pressure drop when standing up from sitting or lying down — a condition called orthostatic hypotension (OH) — in patients when they were not taking medication. Urinary incontinence was linked to OH when patients were on treatment.

These findings suggest that older Parkinson’s patients on levodopa should be routinely monitored for blood pressure changes, particularly those using higher doses, the researchers noted.

The study, “Effects of different levodopa doses on blood pressure in older patients with early and middle stages of Parkinson’s disease,” was published in Heliyon.

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Low blood pressure or sudden drops more common in later Parkinson’s stages

Orthostatic hypotension is a fairly common nonmotor Parkinson’s symptom, and it tends to become more prevalent in later disease stages. Its occurrence can be influenced by a number of factors, including the use of levodopa, a first-line Parkinson’s therapy.

Levodopa works to restore levels of dopamine, the brain signaling chemical that’s lost in the disease. Low blood pressure, particularly in older patients, is a known side effect, and people in later Parkinson’s stages may be particularly prone to levodopa-induced OH.

Its effects on blood pressure for older patients in the early to middle stages of the disease has not been well explored, the scientists stated.

Researchers in China examined the effects of various levodopa doses on blood pressure in 83 patients, with an average age of 67.41, in a clinical trial (ChiCTR2200055707) at a Beijing hospital. Most of the adults, 63, were in the early stages of Parkinson’s, and 23 were in its middle stages; their median disease duration was three years.

All participants underwent a levodopa challenge test (LCT) at least 12 hours after stopping the use of any disease treatments, on an empty stomach, and in the absence of any blood pressure medications.

Essentially, this test involves the patient receiving levodopa at a dose about 1.5 times higher than their usual dose of levodopa or its equivalent first thing in the morning. Patients were given oral tablets containing either 125, 250, or 375 mg of levodopa combined with benserazide, which prevents levodopa’s breakdown in the bloodstream.

Blood pressure was evaluated in the period after they had stopped their Parkinson’s medications when motor symptoms were at their worst — called an off state or phase — and again during the peak time of levodopa benefit after LCT was initiated, called the “best on state.”

These measurements were evaluated in the lying down position and again one and three minutes after standing up.

Systolic blood pressure significantly affected at 250 mg or higher doses

Among patients given the two higher levodopa doses (250 or 375 mg), blood pressure decreased significantly on medication compared with the off phase in both the standing up or lying down positions. No changes with the lowest, 125 mg dose were observed.

Systolic blood pressure — the pressure when the heart is contracting during a heartbeat — dropped continuously from the lying to the standing position in patients on the 250 or 375 mg doses, but not the 125 mg dose.

After three minutes of standing, systolic blood pressure was found to be significantly influenced by levodopa dose.

“These results provide evidence for the safety of 125 mg levodopa/benserazide administrations in this subpopulation,” the researchers wrote. Moreover, “[blood pressure] monitoring is critical for older patients … who are tested or treated with 250 mg or more.”

Overall, 19 of the 83 patients (22.9%) experienced OH in the off state, meaning their blood pressure dropped when standing up. But none had overt symptoms of low blood pressure, such as sleepiness, dizziness, fatigue, or blurred vision.

During the “best on state,” 25 patients (30.1%) experienced OH, with two people receiving the highest levodopa dose having significant symptoms of low blood pressure.

Ultimately, no statistically significant differences between OH rates in on or off medication states were seen.

Final analyses indicated that cognitive impairment was a risk factor for a blood pressure drop during off states, whereas off state OH and urinary incontinence were risk factors for orthostatic hypotension during on periods.

Such risk factors “might serve as an early warning sign to identify individuals with potential hypotension [low blood pressure] aggravation,” the scientists noted.