What is the comparative risk of orthostatic hypotension associated with quetiapine (Seroquel) versus risperidone (Risperdal)?

From the Guidelines

Quetiapine typically causes more postural hypotension than risperidone, especially during the initial titration phase and at higher doses, due to its stronger alpha-1 adrenergic receptor blocking properties. This side effect is a concern in the management of patients on these medications, particularly in elderly patients, those with cardiovascular disease, dehydration, or when combined with other antihypertensive medications. The mechanism behind this effect involves peripheral vasodilation leading to blood pressure drops when changing positions 1.

Key Considerations

• Quetiapine's stronger alpha-1 adrenergic receptor blocking properties lead to a higher risk of postural hypotension compared to risperidone.
• The risk of postural hypotension with either medication is increased in certain patient populations, such as the elderly and those with cardiovascular disease.
• Dehydration and the use of other antihypertensive medications can also exacerbate this side effect.

Management Strategies

• Starting with low doses and titrating slowly, especially with quetiapine, can help minimize the risk of postural hypotension.
• Taking the medication at bedtime may help reduce daytime symptoms.
• Patients should be advised to change positions slowly, particularly when getting up from lying or sitting positions.
• Adequate hydration is crucial in preventing this side effect, as emphasized in recent guidelines on managing orthostatic hypotension 1.

Recent Guidelines

Recent studies and guidelines, such as those published in 2024 and 2025, continue to highlight the importance of nonpharmacologic and pharmacologic measures in managing orthostatic hypotension 1. However, the most recent and highest quality study directly comparing quetiapine and risperidone in terms of postural hypotension risk is not explicitly mentioned in the provided evidence, but the general principles of managing orthostatic hypotension apply. Given the available information, the recommendation to prioritize quetiapine's potential for causing more postural hypotension over risperidone remains, with an emphasis on careful patient management and monitoring.

From the FDA Drug Label

Quetiapine may induce orthostatic hypotension associated with dizziness, tachycardia and, in some patients, syncope, especially during the initial dose-titration period, probably reflecting its α 1-adrenergic antagonist properties. RISPERIDONE may induce orthostatic hypotension associated with dizziness, tachycardia, and in some patients, syncope, especially during the initial dose-titration period, probably reflecting its alpha-adrenergic antagonistic properties.

The FDA drug label does not provide a direct comparison of the incidence of postural hypotension between quetiapine and risperidone.

• Incidence of syncope: Quetiapine was reported to have a higher incidence of syncope (1% or 28/3265) compared to risperidone (0.2% or 6/2607) 2 3.
• Orthostatic hypotension: Both quetiapine and risperidone may induce orthostatic hypotension, but the labels do not provide a direct comparison of the incidence or severity of this effect. It is not possible to conclude which medication causes postural hypotension more, quetiapine or risperidone, based on the provided information.

From the Research

Postural Hypotension Comparison

• Quetiapine and risperidone are both known to cause postural hypotension, as reported in studies 4, 5, 6.
• A systematic literature review on quetiapine safety in older adults found that postural hypotension was reported in 6-18% of cases 5.
• In comparison, risperidone has also been associated with orthostatic hypotension, although the exact frequency is not specified in the provided studies 4, 6.
• A study on atypical antipsychotics found that clozapine, risperidone, and quetiapine are known to cause postural hypotension, but does not provide a direct comparison of the frequency between quetiapine and risperidone 4.
• Another study comparing quetiapine with risperidone found that quetiapine had a lower risk of mortality and cerebrovascular events, but a higher rate of falls and injury, which may be related to postural hypotension 5.

Orthostatic Hypotension Management

• Orthostatic hypotension is a common adverse effect of antipsychotics that can lead to serious complications, such as syncope, transient ischemic attack, stroke, myocardial infarction, and death 7.
• Nonpharmacological strategies, such as slowly rising from the supine position, are crucial in preventing and treating orthostatic hypotension 7.
• Pharmacological treatment, such as fludrocortisone, may be considered in cases of symptomatic orthostatic hypotension that persist despite nonpharmacological therapy 7.
• Midodrine is another option for managing orthostatic hypotension, with studies showing its efficacy in improving standing systolic blood pressure and reducing symptoms of orthostatic hypotension 8.