What is the recommended dosage and treatment protocol for Mirtazepine (Remeron) in patients with 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, increase up to a maximum of 45 mg daily, with dose changes made no more frequently than every 1-2 weeks. 1

Initial Dosing Strategy

• Begin with 15 mg once daily, preferably in the evening prior to sleep 1
• The bedtime dosing schedule takes advantage of mirtazapine's sedating properties, which can improve sleep disturbances commonly associated with depression 2, 3
• Do not adjust the dose more frequently than every 1-2 weeks to allow sufficient time for evaluation of therapeutic response 1

Dose Titration Protocol

• If patients do not respond adequately to the initial 15 mg dose, increase up to a maximum of 45 mg per day 1
• The effective dosage range is 15-45 mg daily 4, 2
• Higher doses (above 15 mg) may actually reduce sedation, as the sedating effects are more prominent at subtherapeutic doses 3

Monitoring Timeline

• Begin assessing patient status, therapeutic response, and adverse effects within 1-2 weeks of starting treatment 5, 6
• If no adequate response occurs within 6-8 weeks, modify treatment 5, 6
• Mirtazapine demonstrates a faster onset of action compared to SSRIs like citalopram, fluoxetine, paroxetine, and sertraline, with clinical effects potentially visible within 1-2 weeks 5, 6, 7
• Sleep disturbances and anxiety symptoms may improve within the first week of treatment 2

Treatment Duration

• Continue treatment for 4-9 months after achieving satisfactory response in patients with a first episode of major depressive disorder 5, 6
• For patients with 2 or more previous depressive episodes, consider even longer duration of therapy 5, 6
• This extended maintenance reduces the risk of relapse 5

Special Considerations Before Starting

• Screen all patients for personal or family history of bipolar disorder, mania, or hypomania prior to initiating treatment 1
• Allow at least 14 days between discontinuing an MAOI and starting mirtazapine, and vice versa 1

Dose Adjustments for Drug Interactions

• With strong CYP3A inducers (carbamazepine, phenytoin, rifampin): increase mirtazapine dose 1
• With strong CYP3A inhibitors (ketoconazole, clarithromycin) or cimetidine: decrease mirtazapine dose 1
• Reverse these adjustments if the interacting medication is discontinued 1

Discontinuation Strategy

• Gradually taper the dose rather than stopping abruptly to minimize withdrawal symptoms 1
• Abrupt discontinuation may lead to adverse reactions 1

Clinical Advantages

• Mirtazapine is particularly suitable for patients with depression accompanied by insomnia or weight loss 6
• It promotes sleep, appetite, and weight gain through its antagonism of 5-HT2A, H1, and alpha-1 adrenergic receptors 6, 7
• The medication has minimal anticholinergic, cardiovascular, and serotonergic side effects (no gastrointestinal symptoms or sexual dysfunction) 2, 3

Common Adverse Effects to Monitor

• Sedation/somnolence (most common, particularly at lower doses) 6, 2, 3
• Increased appetite and weight gain 6, 2, 8
• Dry mouth 6
• Constipation or diarrhea 6
• These effects are generally transient and well-tolerated 8

Treatment-Resistant Depression

• If inadequate response to mirtazapine occurs after 6-8 weeks at adequate doses, approximately 38% of patients do not achieve treatment response and 54% do not achieve remission with any second-generation antidepressant 5
• Consider switching to an alternative second-generation antidepressant (bupropion, sertraline, or venlafaxine), as approximately 1 in 4 patients become symptom-free after switching 5