What are the options for a patient on Viibryd (vilazodone) who has tried Vraylar (cariprazine) but reports not feeling as well as they did on Remeron (mirtazapine)?

Switching Back to Mirtazapine (Remeron)

If your patient felt better on mirtazapine (Remeron) than on the current combination of vilazodone (Viibryd) and past trial of cariprazine (Vraylar), switch back to mirtazapine—it is a well-established, effective antidepressant with unique benefits for depression, anxiety, and sleep that may specifically address this patient's symptom profile. 1

Rationale for Returning to Mirtazapine

Efficacy and Unique Properties

• Mirtazapine has demonstrated equivalent efficacy to SSRIs and tricyclic antidepressants in treating major depression, with a notably faster onset of action (significant improvement within 1-2 weeks versus 4 weeks for most SSRIs). 1
• The drug enhances both noradrenergic and serotonergic neurotransmission through alpha-2 receptor blockade while simultaneously blocking 5-HT2 and 5-HT3 receptors, providing antidepressant effects without typical serotonergic side effects like sexual dysfunction or gastrointestinal distress. 2, 3
• Mirtazapine offers additional therapeutic benefits for anxiety and insomnia—common comorbid symptoms in depression—which may reduce the need for additional medications. 4, 1

Comparison to Current Regimen

• All second-generation antidepressants show similar efficacy for major depression, with medication choice appropriately based on patient preference, prior response, and tolerability. 1
• Since your patient reports feeling better historically on mirtazapine, this represents a documented positive treatment response that should guide medication selection. 1
• Vilazodone (Viibryd) is an SSRI with 5-HT1A partial agonist properties designed for faster onset and reduced sexual side effects, but it offers no proven superiority over other antidepressants in head-to-head comparisons. 5

Practical Switching Strategy

Discontinuation and Initiation

• Taper vilazodone over 10-14 days to minimize withdrawal symptoms (common practice for antidepressant discontinuation). 1
• Start mirtazapine at 15 mg at bedtime, then increase to 30 mg after 4 days if tolerated. 1, 6
• If insufficient response after 2-3 weeks at 30 mg, increase to 45 mg daily (maximum recommended dose). 6, 3

Monitoring Considerations

• Assess for early response within 1-2 weeks, as mirtazapine demonstrates faster onset than most SSRIs. 1
• Monitor for common side effects: sedation (typically dose-related and paradoxically less at higher doses), increased appetite, and weight gain (reported in 7.5% of patients with ≥7% body weight gain). 6, 1
• Rare but serious: Check CBC if patient develops fever, sore throat, or signs of infection, as agranulocytosis occurred in 2 of 2796 patients in premarketing trials. 6

Important Safety Considerations

Cardiovascular and QTc Effects

• Mirtazapine shows a positive relationship between drug concentration and QTc prolongation, though not typically at clinically meaningful levels at therapeutic doses. 6
• Exercise caution if your patient has known cardiovascular disease, family history of QT prolongation, or takes other QTc-prolonging medications. 6

Drug Interactions

• Avoid combining with MAOIs (contraindicated due to serotonin syndrome risk). 6
• Monitor for serotonin syndrome if combining with other serotonergic agents, though mirtazapine's 5-HT2 and 5-HT3 blockade may reduce this risk compared to SSRIs. 6
• Mirtazapine is metabolized by CYP1A2, 2D6, and 3A4 but is not a potent inhibitor of these enzymes, minimizing drug-drug interaction concerns. 7, 4

Why Not Continue Current Medications

Vraylar (Cariprazine) Context

• Cariprazine is an atypical antipsychotic approved for bipolar depression and schizophrenia, not typically first-line for unipolar major depression unless augmentation is needed. The patient has already tried and discontinued this.

Patient-Reported Outcome Priority

• Quality of life and patient-reported well-being are critical outcomes in depression treatment. 1
• When a patient identifies a previous medication where they "felt good," and current therapy is inadequate despite trials of multiple agents, returning to the effective medication is clinically appropriate. 1

Duration of Treatment

• Continue mirtazapine for at least 4-6 months after achieving remission for a first depressive episode. 1
• Patients with recurrent depression benefit from prolonged or indefinite maintenance therapy to prevent relapse. 1