Can bupropion (Wellbutrin), sertraline (Zoloft), donepezil, or quetiapine (Seroquel) contribute to hypotension?

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From the Guidelines

Bupropion, sertraline, donepezil, and quetiapine can all potentially contribute to hypotension, with quetiapine posing the highest risk due to its alpha-adrenergic blocking properties, as noted in a 2021 study on polypharmacy management in older patients 1. When considering the potential for these medications to contribute to hypotension, it's essential to evaluate their mechanisms and the populations most at risk.

  • Quetiapine, an atypical antipsychotic, is known for its sedating effects and can cause orthostatic hypotension, particularly during initial titration or at higher doses, due to its alpha-adrenergic blocking properties.
  • Donepezil, a cholinesterase inhibitor used in the treatment of mild to moderate dementia, can increase vagal tone and cause cholinergic effects, leading to hypotension, especially in elderly patients, as its adverse effects include bradyarrhythmia 1.
  • Sertraline, an SSRI, occasionally causes hypotension as a side effect, though it is less common compared to quetiapine.
  • Bupropion, an antidepressant, generally has a lower risk of hypotension and may even slightly increase blood pressure in some patients. It is crucial for patients taking these medications to monitor for symptoms of hypotension, such as dizziness, lightheadedness, or fainting, especially when standing up quickly, and for healthcare providers to consider these risks when prescribing, particularly in elderly patients or those with pre-existing cardiovascular conditions 1. Key factors that increase the risk of hypotension with these medications include higher doses, combination with other blood pressure-lowering drugs, and individual patient characteristics such as age and cardiovascular health. Starting with lower doses and gradually increasing them can help minimize the risk of hypotensive effects, as part of a careful management strategy to balance the benefits of these medications against their potential risks, especially in vulnerable populations like the elderly 1.

From the FDA Drug Label

Overdoses of up to 30 grams or more of bupropion have been reported. Seizure was reported in approximately one third of all cases Other serious reactions reported with overdoses of bupropion alone included hallucinations, loss of consciousness, mental status changes, sinus tachycardia, ECG changes such as conduction disturbances or arrhythmias, clonus, myoclonus, and hyperreflexia Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported mainly when bupropion was part of multiple drug overdoses.

Bupropion can contribute to hypotension, especially in cases of overdose, as reported in the drug label 2.

  • Key points:
    • Bupropion overdose has been associated with hypotension.
    • This effect is more commonly observed when bupropion is taken in combination with other drugs. There is no information in the provided drug label about sertraline, donepezil, or quetiapine, so no conclusion can be drawn about these medications.

From the Research

Medication Effects on Blood Pressure

  • Bupropion:
    • Studies have shown that bupropion is relatively free of cardiac side effects, including orthostatic hypotension, in depressed patients without cardiac disease 3, 4.
    • However, bupropion may cause orthostatic hypotension, especially in patients with cardiovascular diseases, and can lead to blood pressure increases, usually at high doses 5, 6.
  • Sertraline:
    • Selective serotonin reuptake inhibitors, such as sertraline, are characterized by limited effects on autonomic system activity and a lower impact on blood pressure 5.
    • However, sertraline withdrawal can induce orthostatic hypotension, as reported in a case study 7.
  • Donepezil and Quetiapine:
    • There is no direct evidence in the provided studies to suggest that donepezil or quetiapine contribute to hypotension.

Orthostatic Hypotension

  • Orthostatic hypotension is a potential side effect of certain medications, including some antidepressants and antipsychotics.
  • Studies have shown that bupropion and sertraline can cause orthostatic hypotension in some cases, although the risk is generally considered low 3, 4, 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Antidepressant Drugs Effects on Blood Pressure.

Frontiers in cardiovascular medicine, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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