What is the recommended dosage and treatment approach for mirtazapine (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 at bedtime, with gradual titration up to a maximum of 45 mg daily based on clinical response and tolerability. 1

Initial Dosing and Titration

• Start with 15 mg once daily, administered orally in the evening prior to sleep 1
• If patients do not have an adequate response to the initial 15 mg dose, increase the dose up to a maximum of 45 mg per day 1
• Dose changes should not be made in intervals of less than 1-2 weeks to allow sufficient time for evaluation of response 1, 2
• The medication's long half-life (20-40 hours) enables once-daily bedtime dosing 3

Efficacy and Onset of Action

• Mirtazapine is effective for treating major depressive disorder with efficacy comparable to tricyclic antidepressants and other second-generation antidepressants 4, 5
• Mirtazapine has a potentially faster onset of action compared to SSRIs, with initial improvement in symptoms often observed within 1-2 weeks of treatment 2, 3
• Sleep disturbances and anxiety symptoms may improve within the first week of treatment 3
• Full therapeutic effect is typically observed after 4-6 weeks of treatment 2

Mechanism of Action and Unique Properties

• Mirtazapine is a tetracyclic antidepressant with a novel mechanism of action as a noradrenergic and specific serotonergic antidepressant (NaSSA) 6, 5
• It enhances noradrenergic and serotonergic neurotransmission by blocking central α2-adrenergic auto- and heteroreceptors 6, 2
• Mirtazapine directly blocks 5-HT2 and 5-HT3 receptors, which helps reduce common SSRI-related side effects 6, 3
• Unlike many other antidepressants, mirtazapine has a hormonal effect that reduces cortisol levels 2

Common Side Effects and Management

• The most common side effects include somnolence/sedation (23%), dry mouth (25%), increased appetite (11%), and weight gain (10%) 6, 7
• Sedation is most prominent at lower doses (15 mg) due to higher affinity for H1 histamine receptors, and may decrease at higher doses 2
• Mirtazapine has minimal anticholinergic, cardiovascular, and sexual side effects compared to other antidepressants 6, 3
• Monitor for transient elevations in cholesterol levels and liver function tests 2

Duration of Treatment

• Continue treatment for 4-9 months after a satisfactory response in patients with a first episode of major depressive disorder 4
• For patients who have had 2 or more episodes of depression, an even longer duration of therapy may be beneficial 4
• When discontinuing treatment, gradually reduce the dosage rather than stopping abruptly to minimize withdrawal symptoms 1

Special Considerations

• In elderly patients, mirtazapine is considered a preferred agent along with citalopram, escitalopram, sertraline, venlafaxine, and bupropion 4
• For patients with comorbid insomnia, mirtazapine's sedative properties may be particularly beneficial 4
• Mirtazapine is potent and well-tolerated in promoting sleep, appetite, and weight gain, which may be beneficial for patients with depression-related insomnia or weight loss 4
• Mirtazapine may be effective for treating comorbid anxiety disorders, although large, well-designed trials are needed to confirm these findings 5

Drug Interactions and Precautions

• Screen for bipolar disorder prior to initiating treatment 1
• Allow at least 14 days between discontinuation of an MAOI and initiation of mirtazapine, and vice versa 1
• Dosage adjustments may be needed with concomitant use of strong CYP3A inducers or inhibitors 1
• Reduce dose when used with cimetidine 1
• Exercise caution in patients with hepatic or renal insufficiency; careful dosage titration and regular monitoring for adverse events is recommended 6

Treatment Resistance and Alternatives

• If patients do not have an adequate response to pharmacotherapy within 6-8 weeks, treatment modification is recommended 4
• For patients who do not respond to an initial antidepressant, switching to another agent (including mirtazapine) or adding another medication may be considered 4
• Approximately 38% of patients do not achieve a treatment response during 6-12 weeks of treatment with second-generation antidepressants, and 54% do not achieve remission 4

Mirtazapine offers a valuable alternative in the antidepressant armamentarium with its unique mechanism of action, favorable side effect profile for certain patients, and potential for rapid onset of action.