What is the recommended dosage and treatment regimen for Mirtazapine (an antidepressant medication) in patients with major depressive disorder?

Mirtazapine Dosage and Treatment Regimen for Major Depressive Disorder

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

Initial Dosing and Titration

• Start with 15 mg once daily, preferably in the evening prior to sleep 1
• Dose changes should not be made in intervals of less than 1-2 weeks to allow sufficient time for evaluation of response 1
• If patients do not have an adequate response to the initial 15 mg dose, increase the dose gradually up to a maximum of 45 mg per day 1, 2
• The effective daily dosage range is 15-45 mg 3

Treatment Timeline and Response

• Begin assessing therapeutic response and adverse effects within 1-2 weeks of treatment initiation 2
• Clinical effects on sleep disturbances and anxiety symptoms may improve within the first week of treatment 3
• Full antidepressant efficacy is typically observed after 4-6 weeks of treatment 4
• If the patient does not have an adequate response within 6-8 weeks, treatment modification is strongly recommended 2

Duration of Treatment

• Treatment should continue for 4-9 months after a satisfactory response in patients with a first episode of major depressive disorder 2
• For patients who have had 2 or more episodes of depression, a longer duration of therapy may be beneficial 2

Pharmacological Properties and Benefits

• Mirtazapine has a unique mechanism of action as a noradrenergic and specific serotonergic antidepressant (NaSSA) 3
• It antagonizes presynaptic alpha-2 adrenergic receptors and postsynaptic 5-HT2 and 5-HT3 receptors 4
• The elimination half-life of 20-40 hours enables once-daily bedtime dosing 3
• Mirtazapine has a faster onset of action than some SSRIs such as fluoxetine, paroxetine, and sertraline 2
• It is particularly effective for depression accompanied by insomnia or weight loss 2, 5

Common Side Effects and Monitoring

• Most common side effects include somnolence/sedation (particularly at lower doses), increased appetite, weight gain, and dry mouth 4, 6
• Sedation is more pronounced at lower doses (15 mg) and may decrease at higher doses 7
• Minimal cardiovascular and anticholinergic effects 3
• Lacks typical serotonergic side effects such as gastrointestinal symptoms, insomnia, and sexual dysfunction 3

Special Considerations

• Prior to initiating treatment, screen patients for a personal or family history of bipolar disorder, mania, or hypomania 1
• At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of mirtazapine 1
• Dosage adjustments may be needed with concomitant use of strong CYP3A inducers or inhibitors 1
• Gradually reduce the dosage when discontinuing treatment rather than stopping abruptly 1

Treatment Alternatives

• If inadequate response to mirtazapine occurs, consider switching to an SSRI or SNRI, or adding another antidepressant with a different mechanism of action 2
• For patients with comorbid insomnia, mirtazapine may be particularly beneficial at doses of 15-30 mg at bedtime 5, 2

By following this dosing regimen and monitoring protocol, mirtazapine can be an effective treatment option for patients with major depressive disorder, particularly those with sleep disturbances or weight loss.