What is the recommended dosing for mirtazapine (an antidepressant) for anxiety?

Mirtazapine Dosing for Anxiety

For anxiety treatment, mirtazapine should be started at 15 mg once daily at bedtime, with the option to increase to a maximum of 30-45 mg daily if needed after 1-2 weeks of evaluation. 1

Dosing Recommendations

Initial Dosing

• Start with 15 mg once daily, administered orally in the evening prior to sleep 1
• Lower doses (7.5-15 mg) may be effective for anxiety-related insomnia 2
• Allow 1-2 weeks at each dose level to properly evaluate response before making adjustments 1

Dose Titration

• If inadequate response to 15 mg, increase dose in 15 mg increments
• Maximum recommended dose is 45 mg daily 1
• For anxiety with prominent sleep disturbance, the sedative effects are often more pronounced at lower doses (15 mg), while antidepressant and anxiolytic effects may require higher doses (30-45 mg) 2

Therapeutic Plasma Concentration

• Target plasma concentration range for mirtazapine is 40-80 ng/mL 2
• This is considered a "Level 3" recommendation (useful) based on steady-state pharmacokinetic studies 2

Clinical Considerations

Mechanism for Anxiety Relief

Mirtazapine's anxiolytic effects result from:

• Antagonism at 5-HT2 and 5-HT3 receptors 3
• Alpha-2 adrenergic receptor blockade increasing norepinephrine and serotonin transmission 3
• H1 receptor antagonism contributing to sedation 3

Benefits for Anxiety Treatment

• Rapid onset of anxiolytic action, often within 1-2 weeks 3
• Particularly effective for anxiety with comorbid insomnia 2
• Does not cause sexual dysfunction commonly seen with SSRIs 3
• Promotes sleep and appetite, which can be beneficial in anxiety disorders 4

Common Side Effects

• Somnolence (most common, especially at lower doses) 4
• Increased appetite and weight gain 4
• Dizziness 4
• Dry mouth 3

Special Considerations

Monitoring

• Evaluate response after 1-2 weeks at each dose level 1
• Monitor for excessive sedation, especially at initiation
• Watch for weight gain, which may be problematic in some patients 3

Discontinuation

• Gradually reduce the dosage rather than stopping abruptly to prevent withdrawal symptoms 1
• Taper over 10-14 days when discontinuing treatment 1

Drug Interactions

• Allow at least 14 days between discontinuing MAOIs and starting mirtazapine 1
• Dose adjustments may be needed with strong CYP3A inducers or inhibitors 1

Clinical Pitfalls to Avoid

• Don't expect immediate full anxiolytic effect; while sedation occurs quickly, full anxiolytic benefits may take 2-4 weeks
• Don't overlook the paradoxical effect that lower doses (15 mg) are often more sedating than higher doses (30-45 mg) due to differential receptor occupancy
• Avoid abrupt discontinuation which can lead to withdrawal symptoms
• Be cautious in patients with sleep apnea as weight gain may worsen this condition

While specific data for anxiety disorders are more limited than for depression, mirtazapine's pharmacological profile makes it a valuable option for treating anxiety, particularly when insomnia is a prominent symptom.