Does mirtazapine (Remeron) 7.5mg cause more sedation than 15mg due to altered bioavailability when the tablet is split?

From the Guidelines

No, Remeron (mirtazapine) 7.5mg does not cause more sedation than 15mg because the tablet is broken in half. The increased sedation at lower doses is due to mirtazapine's unique pharmacological profile. At lower doses (7.5mg), mirtazapine primarily blocks histamine H1 receptors, which causes significant sedation. As the dose increases to 15mg and higher, mirtazapine begins to block serotonin 5-HT2 and 5-HT3 receptors more effectively, which actually counteracts some of the sedative effects. Additionally, at higher doses, mirtazapine increases norepinephrine activity, which has an activating effect. This is why many patients experience more sedation at 7.5mg than at 15mg or 30mg, regardless of whether they take a specifically manufactured 7.5mg tablet or half of a 15mg tablet.

Key Points to Consider

• Mirtazapine's sedative effects are dose-dependent, with lower doses causing more sedation due to histamine H1 receptor blockade 1.
• Higher doses of mirtazapine (15mg and above) may actually reduce sedation due to increased blockade of serotonin 5-HT2 and 5-HT3 receptors and increased norepinephrine activity.
• The choice of mirtazapine dose should be based on the patient's response to the medication, with consideration of factors such as sedation, insomnia, and depression.
• According to the clinical guideline for the evaluation and management of chronic insomnia in adults, sedating low-dose antidepressants like mirtazapine may be considered for patients with comorbid depression or treatment failures 1.

Clinical Implications

• Clinicians should be aware of the dose-dependent sedative effects of mirtazapine and adjust the dose accordingly to minimize sedation and maximize therapeutic benefits.
• Patients experiencing excessive sedation at lower doses of mirtazapine may benefit from a dose increase, while those experiencing residual sedation at higher doses may require a dose reduction.
• Mirtazapine's unique pharmacological profile makes it a useful treatment option for patients with insomnia and depression, and its dose-dependent effects should be carefully considered in clinical practice.

From the Research

Mirtazapine Sedation and Bioavailability

• The provided studies do not directly address the issue of altered bioavailability when mirtazapine tablets are split, and its effect on sedation 2, 3, 4, 5, 6.
• Mirtazapine is known to cause sedation, which is one of its most common side effects, particularly at lower doses 4, 5, 6.
• The sedative effects of mirtazapine are thought to be related to its antagonism of the 5-HT2 and 5-HT3 receptors, as well as its affinity for histamine H1 receptors 5.
• There is no clear evidence to suggest that splitting mirtazapine tablets would alter its bioavailability in a way that would increase sedation at lower doses, such as 7.5mg compared to 15mg 2, 3, 4, 5, 6.
• The bioavailability of mirtazapine is approximately 50%, and peak plasma concentrations are reached within 2.2 to 3.1 hours after single oral doses of 15 to 75mg, which are dose-dependent 5.

Mirtazapine Dosage and Sedation

• Mirtazapine is typically administered in doses ranging from 15 to 45mg once daily, with a long half-life that allows for once-daily dosing 2, 3, 4, 5, 6.
• The recommended starting dosage of mirtazapine is 15 mg/day, which can be increased to 30 mg/day and then to 45 mg/day if necessary 5.
• Sedation is more commonly reported at lower doses, and it is recommended to start with a dose of 15 mg/day to minimize sedative effects 4, 5, 6.