Medication Regimen Optimization for Motivation Deficits
Consider optimizing the Auvelity (dextromethorphan/bupropion) dose first, as this combination has demonstrated rapid antidepressant effects within 2 weeks and specifically targets motivation through dopaminergic and noradrenergic mechanisms. 1, 2
Current Regimen Assessment
The patient is on a complex polypharmacy regimen that may be contributing to motivational deficits:
- Vraylar (cariprazine) - While effective for negative symptoms in schizophrenia, can cause akathisia/restlessness and fatigue 1
- Duloxetine - SNRI with proven efficacy for depression 3
- Buspirone - Anxiolytic with minimal activating properties 3
- Auvelity - Novel combination with dopaminergic effects that may specifically address motivation 1, 2
Primary Recommendation: Optimize Auvelity Dosing
Ensure Auvelity is dosed at the therapeutic target of 45 mg dextromethorphan/105 mg bupropion twice daily. 1, 2 This combination:
- Produces significant reductions in depressive symptoms within 2 weeks 2
- Achieves remission rates approaching 70% in long-term studies 2
- Bupropion's dopaminergic and noradrenergic effects specifically target apathy and motivation 4
- Dextromethorphan's NMDA antagonism and sigma-1 agonism provide additional antidepressant mechanisms 1, 2
Secondary Considerations
Evaluate Vraylar's Role
If positive symptoms are well-controlled, consider gradual dose reduction of Vraylar while remaining within therapeutic range. 3 Cariprazine's most common side effects include akathisia/restlessness and fatigue, which could contribute to the patient's need to "make herself do things." 1
- The approved adjunctive dose for depression is 1.5 mg daily 1
- Higher doses (3 mg) were less consistently effective 1
- Consider whether the antipsychotic is still necessary if treating depression alone
Monitor for Drug-Drug Interactions
Be vigilant for potential interactions between duloxetine and bupropion (both CYP2D6 inhibitors), which can elevate hydroxybupropion levels and increase dopaminergic effects. 5 While this interaction is generally well-tolerated, it requires monitoring for:
- Excessive activation or agitation
- Sleep disturbances
- In elderly patients, increased delirium risk 5
Augmentation Strategy If Inadequate Response
If optimizing Auvelity dosing proves insufficient after 4-6 weeks:
Consider augmenting with bupropion monotherapy (separate from Auvelity) up to 300-450 mg daily total, as higher bupropion doses specifically target apathy and reduced energy. 4 Bupropion is described as "activating" and can produce "rapid improvement of energy level." 3
Alternatively, augmentation with low-dose stimulants could be considered if the patient meets criteria for attention deficits contributing to motivation problems. 3 However, this would require careful assessment for ADHD symptoms beyond simple amotivation.
Monitoring Parameters
- Assess target symptoms weekly during titration via telephone contact 3
- Monthly follow-up appointments until symptoms stabilize 3
- Systematic assessment of side effects including insomnia, agitation, and akathisia 3, 1
- Self-ratings from the patient regarding energy, motivation, and functional capacity 3
Critical Pitfalls to Avoid
Do not add additional antidepressants without first optimizing existing medications. 3 Low-quality evidence shows no significant difference between switching versus augmenting strategies, but augmenting with bupropion showed better depression severity reduction than buspirone. 3
Avoid assuming all motivational deficits are treatment-resistant depression. Consider whether cariprazine-induced side effects (fatigue, akathisia) are masquerading as or exacerbating the underlying motivational problem. 1
Do not discontinue Auvelity abruptly - bupropion requires tapering, and the combination should be managed carefully given the CYP2D6 inhibition effects. 4, 5