What is the recommended dosage and treatment protocol for mirtazapine in treating major depressive disorder?

Mirtazapine Dosing and Treatment Protocol for Major Depressive Disorder

Start mirtazapine at 15 mg once daily at bedtime, and if inadequate response occurs, titrate up to a maximum of 45 mg daily, with dose changes made no more frequently than every 1-2 weeks. 1

Initial Dosing and Titration

• Begin with 15 mg orally once daily, preferably in the evening prior to sleep 1
• If patients do not achieve adequate response at 15 mg, increase the dose up to a maximum of 45 mg per day 1
• Wait at least 1-2 weeks between dose adjustments to allow sufficient time to evaluate response to each dose level 1
• The effective dose range is 15-45 mg once daily, with the long half-life (20-40 hours) supporting once-daily bedtime dosing 2

Timeline for Response Assessment

• Begin assessing therapeutic response and adverse effects within 1-2 weeks of treatment initiation 3
• Mirtazapine demonstrates a faster onset of action compared to SSRIs like fluoxetine, paroxetine, and sertraline, with some patients showing improvement in sleep disturbances and anxiety within the first week 4, 3, 2
• Clinical antidepressant effect typically occurs within 2-4 weeks 2
• If inadequate response occurs within 6-8 weeks, treatment modification is strongly recommended 3

Duration of Treatment

• Continue treatment for 4-9 months after achieving satisfactory response in patients with a first episode of major depressive disorder 3
• For patients with 2 or more prior depressive episodes, consider even longer duration of therapy to prevent relapse 3

Pre-Treatment Screening

• Screen all patients for personal or family history of bipolar disorder, mania, or hypomania before initiating mirtazapine 1

Drug Interactions Requiring Dose Adjustment

• With strong CYP3A inducers (carbamazepine, phenytoin, rifampin): Increase mirtazapine dose; decrease dose if inducer is discontinued 1
• With strong CYP3A4 inhibitors (ketoconazole, clarithromycin): Decrease mirtazapine dose; increase dose if inhibitor is discontinued 1
• With cimetidine: Decrease mirtazapine dose; increase dose if cimetidine is discontinued 1

MAOI Interactions

• Allow at least 14 days between discontinuing an MAOI and starting mirtazapine 1
• Allow at least 14 days after stopping mirtazapine before starting an MAOI 1

Common Side Effects to Monitor

• Sedation/somnolence is the most common side effect due to H1 receptor antagonism 3, 5, 2
• Increased appetite and weight gain occur frequently 3, 5, 2
• Dry mouth 3
• Dizziness 5
• Transient elevations in cholesterol levels and liver function tests 5
• Sleep disorders, constipation, or diarrhea 3

Clinical Advantages

• Particularly suitable for patients with depression accompanied by insomnia or weight loss, as mirtazapine promotes sleep, appetite, and weight gain 3
• Effective for patients with depression and anorexia 3
• Minimal cardiovascular and anticholinergic effects 2
• Essentially lacks serotonergic side effects such as gastrointestinal symptoms and sexual dysfunction 2

Treatment-Resistant Depression

• Approximately 38% of patients do not achieve treatment response during 6-12 weeks of second-generation antidepressant treatment 4
• If inadequate response to mirtazapine occurs, consider switching to an SSRI or SNRI, or adding another antidepressant with a different mechanism of action 3
• Mirtazapine showed symptomatic improvement in 38% of treatment-resistant depression patients in open-label studies at a mean dose of 36.7 mg/day 6

Discontinuation

• Gradually reduce the dosage rather than stopping abruptly whenever possible to minimize withdrawal symptoms 1

Safety in Overdose

• Overdoses up to 975 mg caused significant sedation but no cardiovascular or respiratory effects or seizures 2