What is the recommended dosage and treatment approach for Mirtazepine (Remeron) in patients with major depressive disorder?

Mirtazapine Dosage and Treatment Approach for Major Depressive Disorder

The recommended starting dose of mirtazapine for major depressive disorder is 15 mg once daily, administered orally in the evening prior to sleep, with dose increases up to a maximum of 45 mg per day based on clinical response. 1

Initial Dosing and Titration

• Begin with 15 mg once daily in the evening before bedtime 1
• If patients do not have an adequate response to the initial 15 mg dose, increase the dose gradually 1
• Dose changes should not be made in intervals of less than 1-2 weeks to allow sufficient time for evaluation of response 1
• Maximum recommended dose is 45 mg per day 1, 2

Monitoring and Treatment Duration

• Begin assessing patient status, therapeutic response, and adverse effects within 1-2 weeks of treatment initiation 3, 2
• If the patient does not have an adequate response within 6-8 weeks, treatment modification is strongly recommended 3, 2
• Continue treatment for 4-9 months after a satisfactory response in patients with a first episode of major depressive disorder 3, 2
• For patients who have had 2 or more episodes of depression, an even longer duration of therapy may be beneficial 3, 2

Clinical Efficacy and Onset of Action

• Mirtazapine is a potent and well-tolerated antidepressant that promotes sleep, appetite, and weight gain 3, 2
• Patients typically show significant improvement in symptoms of major depressive disorder within the first 1-2 weeks of treatment 4
• Long-term studies at 40 weeks show continued improvements in response rates and lower relapse rates 4
• Mirtazapine has a faster onset of action than some SSRIs, such as fluoxetine, paroxetine, and sertraline 2, 5

Mechanism of Action

• Mirtazapine enhances norepinephrine and serotonin neurotransmission by blocking alpha-2 presynaptic adrenoceptors 4, 5
• It also blocks 5-HT2 and 5-HT3 receptors, which contributes to its sedative properties and reduced side effect profile compared to SSRIs 4, 5
• The enhancement of both noradrenergic and 5-HT1 receptor-mediated neurotransmission is thought to be responsible for its antidepressant activity 5

Side Effects and Management

• Common side effects include:

  • Sedation/drowsiness (most common) 3, 4
  • Increased appetite and weight gain 3, 2, 4
  • Dry mouth 2, 4
  • Dizziness 4
  • Transient elevations in cholesterol levels and liver function tests 4

• Contrary to common belief, higher doses of mirtazapine do not appear to increase the risk of noradrenergic side effects like anxiety, agitation, or tachycardia 6

Special Considerations

• For patients with hepatic or renal insufficiency, careful dosage titration and close monitoring for adverse events is recommended 5
• Screen patients for a personal or family history of bipolar disorder, mania, or hypomania prior to initiating treatment 1
• At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of mirtazapine 1
• Gradually reduce the dosage when discontinuing treatment rather than stopping abruptly to minimize withdrawal symptoms 1

Augmentation Strategy

• For patients with inadequate response to other antidepressants, mirtazapine can be used as an augmentation strategy 7
• When used as augmentation therapy, begin at 15 mg at bedtime with possible titration to 30 mg after week 1 7
• Augmentation with mirtazapine has shown response rates of 64% compared to 20% with placebo 7

Specific Patient Populations

• Mirtazapine is particularly suitable for patients with depression accompanied by:
  • Insomnia or sleep disturbances 3, 2
  • Weight loss or poor appetite 3, 2
  • Anxiety symptoms 2, 8

By following this dosing and treatment approach, clinicians can optimize the therapeutic benefits of mirtazapine while minimizing potential side effects in patients with major depressive disorder.