Is it advisable to add Rexulti (brexpiprazole) or N-acetylcysteine (NAC) to the treatment regimen of a patient with bipolar disorder, anxiety, and obsessive-compulsive disorder (OCD) who is currently taking Vraylar (cariprazine) 1.5 mg and Wellbutrin XL (bupropion) 150 mg for their OCD symptoms?

Adding Rexulti or NAC for OCD in a Patient on Vraylar and Wellbutrin

For OCD augmentation in this patient already on Vraylar (cariprazine) for bipolar disorder, neither Rexulti (brexpiprazole) nor NAC should be added—instead, optimize the current regimen by adding an SSRI at maximum tolerated doses for at least 8 weeks, as SSRIs are the established first-line pharmacological treatment for OCD. 1

Why Not Rexulti or NAC?

Rexulti (Brexpiprazole) Concerns

• Rexulti lacks FDA approval or robust evidence for OCD treatment 2
• Adding a second atypical antipsychotic (Rexulti) to Vraylar creates unnecessary polypharmacy risk without established benefit for OCD 1
• While atypical antipsychotics (AAPs) have a role in OCD, they are reserved for augmentation of SSRIs in treatment-resistant cases, not as primary OCD treatment 1
• Brexpiprazole has not been studied in OCD, unlike aripiprazole which has some evidence in SSRI-refractory OCD 2
• Combining two antipsychotics from the same class has limited empirical support and increases metabolic and neurological side effect risks 1

NAC (N-Acetylcysteine) Concerns

• NAC is classified as a "glutamate modulating agent" in OCD treatment algorithms but is positioned for treatment-resistant cases only 1
• NAC appears in guidelines only after failure of multiple SSRIs, clomipramine, and adequate CBT trials 1
• The evidence base for NAC in OCD is substantially weaker than for SSRIs

The Correct Approach: SSRI Addition

First-Line Treatment for OCD

SSRIs are the established first-line pharmacological treatment for OCD with the strongest evidence base 1:

• Higher doses than used for depression are required: Maximum recommended or tolerated doses for at least 8 weeks 1
• Effect sizes favor SSRIs: Number needed to treat is 5 for SSRIs in OCD 1
• All SSRIs show similar efficacy for OCD, so selection should be based on side effect profile, drug interactions, and past response 1

Managing Bipolar Disorder Concerns

The presence of bipolar disorder requires caution but does not preclude SSRI use 1:

• Vraylar (cariprazine) provides mood stabilization: This patient is already on an effective mood stabilizer with antimanic properties 3, 4
• SSRIs can be used in bipolar disorder when adequate mood stabilization is present 1
• Monitor for mood destabilization: Watch for hypomanic/manic switches, but the risk is mitigated by concurrent Vraylar 5
• Wellbutrin (bupropion) is already present: This activating antidepressant is being tolerated, suggesting the mood stabilization from Vraylar is adequate 1

Specific SSRI Recommendations

Choose an SSRI considering 1:

• Sertraline or fluoxetine: Well-tolerated with fewer drug interactions 1
• Start low, titrate to maximum tolerated doses: For example, sertraline 50 mg daily, increasing to 200 mg daily over 4-6 weeks 1
• Duration: Maintain maximum dose for at least 8-12 weeks before assessing response 1

Treatment Algorithm for This Patient

Step 1: Add SSRI to Current Regimen

• Continue Vraylar 1.5 mg (mood stabilization) 3, 4
• Continue Wellbutrin XL 150 mg (depression/anxiety) 1
• Add SSRI at therapeutic OCD doses (e.g., sertraline up to 200 mg or fluoxetine up to 80 mg) 1

Step 2: If Inadequate Response After 8-12 Weeks

• Switch to different SSRI or try clomipramine 1
• Add CBT with exposure and response prevention (ERP): 10-20 sessions, which has superior efficacy to medication alone 1

Step 3: If Still Treatment-Resistant

• Consider AAP augmentation (but not Rexulti—use agents with OCD evidence like low-dose aripiprazole or risperidone) 1, 2
• Consider glutamate modulators like NAC only at this stage 1

Critical Pitfalls to Avoid

Do not combine two atypical antipsychotics without clear rationale 1:

• The patient is already on Vraylar for bipolar disorder
• Adding Rexulti creates unnecessary polypharmacy
• No evidence supports this combination for OCD

Do not use NAC as first-line treatment 1:

• NAC is reserved for treatment-resistant OCD
• SSRIs must be tried first at adequate doses and duration

Do not neglect psychotherapy 1:

• CBT with ERP has a number needed to treat of 3, superior to medication 1
• Combined SSRI + CBT provides optimal outcomes 1

Monitor for medication interactions 1:

• Wellbutrin can lower seizure threshold at higher doses
• Some SSRIs inhibit cytochrome P450 enzymes affecting other medications
• Vraylar is metabolized by CYP3A4—choose SSRIs with minimal CYP3A4 interaction