What is the likelihood of mirtazapine (Remeron) inducing hypotension?

From the Guidelines

Mirtazapine is likely to drop blood pressure, particularly orthostatic hypotension, due to its blockade of alpha-1 adrenergic receptors, which can cause blood vessels to dilate and reduce peripheral resistance. This effect is most common during the initial treatment period and at higher doses, especially in elderly patients, those with pre-existing cardiovascular conditions, or patients taking other medications that lower blood pressure 1. The risk of orthostatic hypotension is a significant concern, and patients starting mirtazapine should be advised to rise slowly from sitting or lying positions, stay well-hydrated, and report symptoms like dizziness, lightheadedness, or fainting. Some key points to consider when prescribing mirtazapine include:

• Lower starting doses (such as 7.5 or 15 mg) may help minimize this side effect, with gradual increases as tolerated.
• Blood pressure monitoring is recommended, particularly during the initiation phase of treatment.
• Patients with a history of cardiovascular disease, such as those discussed in the context of cardiovascular autonomic neuropathy in diabetes 2, 3, may be at increased risk of orthostatic hypotension and should be closely monitored. It is essential to weigh the potential benefits of mirtazapine against its risks, particularly in patients with pre-existing cardiovascular conditions or those taking other medications that may interact with mirtazapine 1.

From the FDA Drug Label

Mirtazapine also acts as an antagonist of histamine (H1) receptors, peripheral α1-adrenergic receptors, and muscarinic receptors. Actions at these receptors may explain some of the other clinical effects of mirtazapine (e.g., its prominent somnolent effects and orthostatic hypotension may be explained by its inhibition of histamine (H1) receptors and peripheral α1-adrenergic receptors, respectively). Mirtazapine tablets were associated with significant orthostatic hypotension in early clinical pharmacology trials with normal volunteers Orthostatic hypotension was infrequently observed in clinical trials with depressed patients [see Adverse Reactions (6. 1)].

Mirtazapine is likely to drop blood pressure due to its action as an antagonist of peripheral α1-adrenergic receptors, which may cause orthostatic hypotension. This effect was observed in early clinical pharmacology trials with normal volunteers and infrequently in clinical trials with depressed patients [4] [5]. Caution should be used when prescribing mirtazapine to patients with known cardiovascular or cerebrovascular disease that could be exacerbated by hypotension. Key points to consider:

• Orthostatic hypotension may occur due to mirtazapine's inhibition of peripheral α1-adrenergic receptors
• Caution is advised when prescribing mirtazapine to patients with cardiovascular or cerebrovascular disease
• Mirtazapine's effect on blood pressure should be monitored in patients at risk of hypotension.

From the Research

Mirtazapine and Blood Pressure

• Mirtazapine is a tetracyclic antidepressant that increases noradrenergic and serotonergic neurotransmission via blockade of central α2-adrenergic auto- and heteroreceptors 6.
• The effect of mirtazapine on blood pressure is not explicitly stated in the provided studies, but its mechanism of action suggests that it may have an impact on blood pressure regulation.
• Analysis of blood pressure, heart rate, and symptoms of sexual dysfunction indicated no significant differences between mirtazapine and placebo recipients in clinical trials 6.

Orthostatic Hypotension

• Orthostatic hypotension is an excessive fall in blood pressure while standing, and it can be caused by various factors, including neurogenic and non-neurogenic causes 7, 8, 9.
• The management of orthostatic hypotension involves non-pharmacological measures, such as increasing fluid and salt intake, and pharmacological options, such as fludrocortisone, midodrine, and droxidopa 7, 8, 9.
• Mirtazapine is not mentioned as a treatment option for orthostatic hypotension in the provided studies.

Conclusion on Mirtazapine and Blood Pressure Drop

• There is no direct evidence in the provided studies to suggest that mirtazapine is likely to drop blood pressure.
• However, mirtazapine's mechanism of action and its effects on noradrenergic and serotonergic neurotransmission may have an indirect impact on blood pressure regulation 6.
• Further studies are needed to determine the effects of mirtazapine on blood pressure and its potential use in the management of orthostatic hypotension.