What is the effect of dextromethorphan on Hypertension (HTN)?

From the Guidelines

Dextromethorphan should be used with caution in patients with hypertension (HTN), as it may potentially raise blood pressure, especially at higher doses or when combined with certain medications. While it can be taken by most hypertensive patients at recommended doses, patients with controlled hypertension can generally use standard over-the-counter doses (typically 10-30 mg every 4-6 hours, not exceeding 120 mg daily) for short periods. However, those with severe or unstable hypertension should consult their healthcare provider before using dextromethorphan. The caution stems from dextromethorphan's weak serotonergic and adrenergic effects, which can theoretically contribute to blood pressure elevation, as noted in the 2022 World Health Organization guideline executive summary 1.

Particular care should be taken when combining dextromethorphan with monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), or decongestants like pseudoephedrine, as these combinations may further increase blood pressure. Patients should monitor their blood pressure when starting dextromethorphan and report any significant increases to their healthcare provider. According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline, certain medications, including decongestants, can cause elevated blood pressure 1.

The 2018 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline also highlights the importance of considering the benefits and harms of specific blood pressure targets with the patient, which is relevant when prescribing dextromethorphan to patients with hypertension 1. The American College of Physicians and American Academy of Family Physicians joint guideline on pharmacologic treatment of hypertension in adults aged 60 years or older also emphasizes the need for individualized assessment and consideration of treatment burden and drug interactions when deciding on treatment options 1.

In terms of managing hypertension, the 2007 American Heart Association scientific statement provides recommendations for the treatment of hypertension in patients with heart failure, including the use of diuretics, ACE inhibitors, β-blockers, and aldosterone receptor antagonists 1. However, the primary concern with dextromethorphan in patients with hypertension is its potential to raise blood pressure, and patients should be advised to monitor their blood pressure and report any significant increases to their healthcare provider.

Key considerations for patients with hypertension taking dextromethorphan include:

• Monitoring blood pressure regularly
• Reporting any significant increases in blood pressure to their healthcare provider
• Avoiding combinations with MAOIs, SSRIs, or decongestants like pseudoephedrine
• Consulting their healthcare provider before using dextromethorphan if they have severe or unstable hypertension. The 2006 ACCP evidence-based clinical practice guidelines provide information on the use of dextromethorphan as a cough suppressant, but do not specifically address its use in patients with hypertension 1.

From the Research

Dextromethorphan and Hypertension

• Dextromethorphan (DXM) has been studied in combination with amlodipine (AM) for the treatment of hypertension, with results showing that low-dose DXM can improve blood pressure reduction in hypertensive patients 2.
• The combination of DXM with AM has been shown to be effective in reducing blood pressure, with a responder rate of 47% in nonresponders to AM monotherapy, and a mean systolic blood pressure reduction of 7.9% with DXM 2.5mg/day 2.
• DXM has also been shown to have antioxidant and endothelial-protective effects, which may contribute to its antihypertensive effects 3.
• The use of DXM in hypertensive patients has been explored in various studies, with results suggesting that it may be a useful adjunctive treatment for hypertension, particularly in patients with impaired endothelial function 2, 3.
• However, it is worth noting that DXM is not typically used as a primary treatment for hypertension, and its use in this context is still being researched and explored 4, 5.

Mechanism of Action

• DXM has been shown to inhibit NADPH oxidase, which may contribute to its antihypertensive effects by reducing vascular oxidative stress and improving endothelial function 3.
• The combination of DXM with AM may have additive effects on blood pressure reduction, and may also improve vascular protection by reducing aortic wall thickness and improving endothelial function 2, 3.

Clinical Implications

• The use of DXM in combination with AM may be a useful treatment strategy for hypertensive patients who do not respond to AM monotherapy 2.
• Further research is needed to fully explore the potential benefits and risks of using DXM in the treatment of hypertension, particularly in patients with impaired endothelial function 2, 3.