Can Vraylar (cariprazine) be used to augment bupropion in a patient with treatment-resistant depression and anxiety?

Vraylar (Cariprazine) as Augmentation for Bupropion in Treatment-Resistant Depression with Anxiety

Vraylar (cariprazine) is an effective augmentation strategy for bupropion in patients with treatment-resistant depression and anxiety, with FDA approval specifically for adjunctive treatment of major depressive disorder. 1

Evidence for Cariprazine as an Augmentation Agent

• Vraylar has demonstrated efficacy as an adjunctive therapy to antidepressants for treatment-resistant major depressive disorder in two large clinical trials with patients who had inadequate response to 1-3 courses of prior antidepressant therapy 1
• In a 6-week placebo-controlled trial (N=751), Vraylar 1.5 mg/day + antidepressant therapy was superior to placebo + antidepressant therapy in reducing Montgomery-Asberg Depression Rating Scale (MADRS) scores 1
• In an 8-week placebo-controlled trial (N=808), Vraylar 2-4.5 mg/day (mean dose 2.6 mg) + antidepressant therapy was superior to placebo + antidepressant therapy in reducing MADRS scores 1

Dosing Recommendations for Adjunctive Treatment

• For adjunctive treatment of major depressive disorder, the recommended dosage of Vraylar is 1.5 mg/day, with evidence showing this dose was statistically significantly superior to placebo 1
• Higher doses (2-4.5 mg/day) have also shown efficacy but should be carefully considered as doses above 6 mg daily do not confer increased effectiveness sufficient to outweigh dose-related adverse reactions 1
• Start with lower doses and titrate based on clinical response and tolerability 1

Bupropion in Treatment-Resistant Depression

• Bupropion functions as a norepinephrine and dopamine reuptake inhibitor and is FDA-approved for treatment of major depressive disorder 2
• Bupropion can be used as an augmentation strategy when initial treatment with SSRIs fails, as recommended by the American College of Physicians 2
• When augmenting citalopram treatment for depression, bupropion decreases depression severity more than buspirone, with lower discontinuation rates due to adverse events 2

Comparative Effectiveness of Augmentation Strategies

• Recent meta-analysis suggests that augmentation with aripiprazole (another atypical antipsychotic like cariprazine) may be a better comprehensive antidepressant treatment strategy than augmentation with bupropion for patients with treatment-resistant depression 3
• Low-quality evidence from trials showed no difference in response or remission for augmentation of citalopram treatment with bupropion compared with augmentation with buspirone, though bupropion decreased depression severity more than buspirone 4
• For patients with anxiety symptoms accompanying depression, second-generation antidepressants did not differ significantly in efficacy, though venlafaxine may be superior to fluoxetine 4

Benefits of Cariprazine-Bupropion Combination

• The combination provides complementary mechanisms of action: bupropion affects norepinephrine and dopamine, while cariprazine acts as a partial agonist at dopamine D2/D3 receptors 2, 1
• This combination may be particularly beneficial for patients with both depression and anxiety symptoms, as both medications have shown efficacy in these conditions 4, 1
• Case reports have shown that combining medications with different mechanisms of action can be effective in treatment-resistant depression 5, 6

Potential Risks and Monitoring

• Monitor for akathisia, extrapyramidal symptoms, and metabolic changes with cariprazine 1
• Be aware of bupropion's seizure risk (0.1%), especially at higher doses, and avoid in patients with seizure risk factors 2
• Start with lower doses of cariprazine (1.5 mg daily) when augmenting bupropion to minimize side effects 1
• Regularly assess for treatment response using standardized measures like the MADRS 1

Clinical Pearls

• The combination may be particularly useful for patients with prominent anhedonia or lack of motivation, given the dopaminergic effects of both medications 2, 6
• Consider this combination when patients have had an inadequate response to at least 1-3 courses of prior antidepressant therapy 1
• Bupropion has the advantage of minimal sexual side effects compared to many other antidepressants, making this combination potentially better tolerated 2
• The evidence supports cariprazine as an effective augmentation strategy with demonstrated efficacy in FDA trials, whereas some other augmentation strategies have more limited evidence 1