Hypertension independently reduces renal lithium excretion and elevates both the concentration-to-dose ratio and the risk of lithium toxicity in patients with manic episodes, with elderly hypertensive patients showing the most pronounced effects.
Key Findings
Results
The hypertension group had significantly higher steady-state serum lithium concentrations and concentration-to-dose (C/D) ratios than the non-hypertension group.
Study enrolled 210 patients with mania: hypertension group (n=90) and non-hypertension group (n=120)
Difference in steady-state serum lithium concentrations and C/D ratios was statistically significant (p < 0.001)
There was no significant difference in mean daily dose of lithium carbonate between the two groups
Single-center retrospective cohort study design
Results
The rate of achieving therapeutic lithium levels was markedly lower in the hypertension group compared to the non-hypertension group.
Therapeutic lithium level achievement rate was only 42.22% in the hypertension group
Therapeutic lithium level achievement rate was 65.83% in the non-hypertension group
This difference represents a gap of more than 23 percentage points between groups
Results
The incidence of lithium toxicity was significantly higher in patients with hypertension than in those without hypertension.
Lithium toxicity incidence was 11.11% in the hypertension group
Lithium toxicity incidence was 2.50% in the non-hypertension group
This represents more than a fourfold difference in toxicity incidence between the groups
Results
Multiple regression analysis confirmed that hypertension, age, and daily dose were independent influencing factors for the lithium C/D ratio.
Hypertension had a regression coefficient of β = 0.215 for the C/D ratio
Age and daily dose were also identified as independent influencing factors
Elderly hypertensive patients showed a more pronounced increase in the C/D ratio
The type of antihypertensive medication did not affect lithium metabolism
Background
Hypertension was found to reduce renal lithium excretion, consistent with the known mechanism of primarily renal lithium clearance.
Lithium carbonate has a narrow therapeutic window and is mainly excreted via the kidneys
Hypertension may impair lithium clearance, and prior evidence from relevant studies was characterized as insufficient
The study was designed to evaluate independent effects of hypertension on steady-state lithium pharmacokinetics
Conclusions
The authors recommend reduced initial lithium dosing, intensified therapeutic drug monitoring, and lower serum concentration targets for hypertensive patients, especially the elderly.
Elderly hypertensive patients were identified as warranting stratified management with lower serum concentration ranges
Recommendations include reducing the initial lithium dose for patients with comorbid hypertension
Intensified therapeutic drug monitoring was recommended for hypertensive patients in clinical practice
What This Means
This research suggests that having high blood pressure (hypertension) significantly changes how the body processes lithium, a medication commonly used to treat manic episodes in bipolar disorder. In a study of 210 patients, those with hypertension had much higher lithium levels in their blood relative to the dose they received, even though they were prescribed similar amounts of lithium as patients without hypertension. This appears to happen because the kidneys — which are responsible for removing lithium from the body — function differently in people with high blood pressure, leading to lithium building up to higher levels than intended.
The practical consequences were substantial: patients with hypertension were far less likely to have their lithium levels fall within the recommended therapeutic range (42% vs. 66%), and they were more than four times as likely to experience lithium toxicity (11% vs. 2.5%). The problem was particularly pronounced in elderly patients with hypertension, who showed the greatest elevation in lithium accumulation. Importantly, the type of blood pressure medication being taken did not appear to influence how lithium was metabolized.
This research suggests that patients who have both hypertension and a condition requiring lithium treatment — such as bipolar disorder with manic episodes — may need more careful management than patients without high blood pressure. Specifically, starting with a lower lithium dose and monitoring blood lithium levels more frequently may help prevent toxic levels from building up, particularly in older patients. Clinicians treating this population may need to adjust their standard dosing and monitoring approaches to account for the altered lithium clearance associated with hypertension.
Liao D, Li M, Xiong Z, Ji Q, Xia Y, Liu B, et al.. (2026). Correlation Analysis of Blood Lithium Metabolism Kinetics and Concentration-to-Dose Ratio in Patients With Hypertension and Manic Episodes.. Human psychopharmacology. https://doi.org/10.1002/hup.70064