Does duloxetine affect blood pressure?

Comment by InpharmD Researcher

While duloxetine has shown significant differences in blood pressure and heart rate in placebo-controlled studies, the effects are minor and not considered clinically significant. A recent meta-analysis also found duloxetine can statistically significantly increase diastolic blood pressure, but the increase is not suspected to be clinically significant. A 2016 case report described a patient who experienced duloxetine-induced hypertension, which is suspected to be a rare adverse event of SNRIs.

  

PubMed: duloxetine hypertension = 59 results

Background

A 2020 systematic review and meta-analysis of 17 studies evaluated the effects of duloxetine on heart rate and blood pressure. The studies evaluated duloxetine for mood disorders (53%) and pain (47%). The studied daily doses of duloxetine were 30 mg, 60 mg, 80 mg, and 120 mg. Hypertension was the most common adverse event with other reported events including myocardial infarction, transient ischemic attack, tachycardia, atrial fibrillation, and cerebrovascular accident. Results of the meta-analysis found significant effects of duloxetine on heart rate (mean difference [MD], 2.22 beats/min; 95% CI, 1.53 to 2.91) and diastolic blood pressure (MD, 0.82 mmHg; 95% CI, 0.17 to 1.47). No significant effect of duloxetine was established on systolic blood pressure (MD, 0.64 mmHg; 95% CI, -0.24 to 1.52). Despite this analysis finding short-term effects of duloxetine on the cardiovascular system, pharmacoepidemiological studies are needed to evaluate the effects of long-term duloxetine use in cardiovascular disease. [1]

Duloxetine is considered to be a relatively balanced serotonin-norepinephrine reuptake inhibitor (SNR), with a 10:1 serotonin:norepinephrine relative affinity. By contrast, venlafaxine has a 31:1 serotonin:norepinephrine relative affinity. In vitro data have found duloxetine can block the cardiac sodium (Na) channel Nav1.5 and the hERG K channel, both have been implicated in drug-induced QT prolongation. However, clinical trials in healthy adults have not found a significant effect of duloxetine on QTc. Due to duloxetine’s noradrenergic properties, it has been shown to increase heart rate slightly and minimally increase systolic blood pressure in healthy adults, but these changes are not deemed to be clinically meaningful. One open-label study of duloxetine 80-120 mg/day in older adults found no changes in blood pressure. A randomized, controlled trial of duloxetine 60 mg/day in older adults found a statistically significant decrease in orthostatic blood pressure of about 3 mmHg in patients receiving duloxetine compared to placebo. Another placebo-controlled trial found a significant increase in diastolic blood pressure from baseline with duloxetine compared with placebo (+1.89 mmHg vs - 1.59 mmHg), but this change was not statistically significant after 24 weeks. Another randomized controlled trial evaluating duloxetine for anxiety found a statistically significant increase in sitting diastolic blood pressure from baseline compared to placebo (+0.3 mmHg vs -1.7 mmHg) and in sitting pulse rate (+1.8 bpm vs -1.3 bpm). Overall, duloxetine may have some risk of orthostatic hypotension in older adults, but it has not demonstrated other cardiovascular adverse events in older populations or in those with cardiovascular disease. [2, 3]

References:

[1] Park K, Kim S, Ko YJ, Park BJ. Duloxetine and cardiovascular adverse events: A systematic review and meta-analysis. J Psychiatr Res. 2020;124:109-114. doi:10.1016/j.jpsychires.2020.02.022
[2] Behlke LM, Lenze EJ, Carney RM. The Cardiovascular Effects of Newer Antidepressants in Older Adults and Those With or At High Risk for Cardiovascular Diseases. CNS Drugs. 2020;34(11):1133-1147. doi:10.1007/s40263-020-00763-z
[3] Shelton RC. Serotonin and Norepinephrine Reuptake Inhibitors. Handb Exp Pharmacol. 2019;250:145-180. doi:10.1007/164_2018_164
Relevant Prescribing Information

Increases in Blood Pressure
In adult placebo-controlled clinical trials across the approved adult populations from baseline to endpoint, duloxetine treatment was associated with mean increases of 0.5 mm Hg in systolic blood pressure and 0.8 mm Hg in diastolic blood pressure compared to mean decreases of 0.6 mm Hg systolic and 0.3 mm Hg diastolic in placebo-treated patients. There was no significant difference in the frequency of sustained (3 consecutive visits) elevated blood pressure. In a clinical pharmacology study designed to evaluate the effects of duloxetine on various parameters, including blood pressure at supratherapeutic doses with an accelerated dose titration, there was evidence of increases in supine blood pressure at doses up to 200 mg twice daily (approximately 3.3 times the maximum recommended dosage).At the highest 200 mg twice daily dose, the increase in mean pulse rate was 5.0 to 6.8 beats and increases in mean blood pressure were 4.7 to 6.8 mm Hg (systolic) and 4.5 to 7 mm Hg (diastolic) up to 12 hours after dosing.
Blood pressure should be measured prior to initiating treatment and periodically measured throughout treatment. [4]

References:

Duloxetine extended-release capsule. Prescribing information. Ascend Laboratories, LLC; 2022.
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Does duloxetine affect blood pressure?

Level of evidence

D - Case reports or unreliable data  Read more→


Please see Table 1 for your response.

 

Duloxetine-Induced Hypertension: A Case Report

Design

 Case report

Case presentation

A 45-year-old female presented with complaints of distress, loss of interest, and insomnia. The patient reported having these complaints for three months and had not consulted a psychiatry clinic before. She was given duloxetine 30 mg/day and alprazolam 0.5 mg/day after being diagnosed with depressive disorder.

Three days after duloxetine initiation, the patient consulted emergency services with complaints of severe headaches. Laboratory parameters were normal, but her blood pressure was 170/110 mm Hg. She was given nifedipine 30 mg/day and recommended for follow-up blood pressure evaluation. 

Her blood pressure decreased to 140/90 mm Hg after nifedipine, but increased again to 160/100 mm Hg. Her nifedipine dose was increased to 60 mg/day, which decreased her blood pressure to 120/80 mm Hg. 

The patient did not have any history of hypertension or cardiovascular disease. After ruling out other potential causes of hypertension, her duloxetine was stopped and she was switched to escitalopram 10 mg/day. At a follow-up appointment after switching antidepressants, she no longer had hypertension. Her nifedipine was tapered and stopped with no increase in blood pressure observed.

Study Author Conclusions

This case report describes severe headaches and increases in blood pressure to 170/110 mmHg without any history of cardiovascular disease, pointing to duloxetine as the causative agent. Cardiovascular adverse events are not common with SNRI use, but case reports of hypertension due to venlafaxine and milnacipran have been reported in the literature.

The probable mechanism of hypertension secondary to SNRIs is an increase in norepinephrine and later on strengthening noradrenergic neurotransmission. The use of venlafaxine is not recommended for patients with hypertension, cardiac dysfunction, coronary artery disease, and EKG anomalies. Although duloxetine is a stronger norepinephrine reuptake inhibitor than venlafaxine, its effects on blood pressure appear to be less pronounced than venlafaxine. Strangely, the risk of increased blood pressure while on duloxetine does not appear to be dose-dependent.

 

References:

Mermi O, Atmaca M. Duloxetine-Induced Hypertension: A Case Report. Turk Psikiyatri Derg. 2016;27(1):67-69.