Alternative Medications to Cariprazine as Antidepressant Adjuncts with Citalopram
If Vraylar (cariprazine) doesn't work as an antidepressant adjunct, aripiprazole should be considered as the first alternative augmentation strategy with citalopram due to its established efficacy and favorable side effect profile.
First-Line Alternative Options
Aripiprazole
- Starting dose: 2-5 mg daily
- Target dose: 5-15 mg daily
- Mechanism: Partial D2 receptor agonist with 5-HT1A partial agonist and 5-HT2A antagonist properties
- Benefits: Well-established efficacy in treatment-resistant depression, relatively lower metabolic side effect burden compared to other atypical antipsychotics 1
- Monitoring: Watch for akathisia (most common side effect), extrapyramidal symptoms
Quetiapine Extended-Release
- Starting dose: 50 mg daily
- Target dose: 150-300 mg daily
- Benefits: FDA-approved for depression, helps with sleep disturbances
- Cautions: More sedation and potential for metabolic issues than aripiprazole
Second-Line Alternative Options
Brexpiprazole
- Starting dose: 0.5-1 mg daily
- Target dose: 2-3 mg daily
- Benefits: Similar to aripiprazole but with potentially lower rates of akathisia
- Considerations: Newer agent with less long-term data
Bupropion
- Starting dose: 150 mg XL daily
- Target dose: 300 mg XL daily
- Benefits: Activating properties that can counteract SSRI-induced fatigue or sexual dysfunction
- Caution: Drug interaction with citalopram - bupropion inhibits CYP2D6 which can increase citalopram levels 2
- Contraindications: Seizure disorders, eating disorders
Algorithm for Selection
Assess symptom profile:
- For predominant anxiety/agitation: Consider quetiapine
- For predominant fatigue/low motivation: Consider aripiprazole or bupropion
- For mixed presentation: Aripiprazole offers balanced profile
Consider comorbidities:
- Bipolar features: Aripiprazole has established efficacy in bipolar disorder 3
- Sleep disturbance: Quetiapine may be more beneficial
- Metabolic concerns: Aripiprazole has more favorable metabolic profile
Evaluate prior response:
- If patient previously responded well to an atypical antipsychotic, consider a different one
- Evidence suggests that failure to respond to one atypical antipsychotic doesn't preclude response to another 4
Important Monitoring Considerations
- Metabolic parameters: Weight, lipids, glucose (especially with quetiapine)
- Movement disorders: Akathisia, extrapyramidal symptoms (especially with aripiprazole)
- QTc interval: Both citalopram and some antipsychotics can prolong QTc interval
- Sexual function: Monitor for worsening of SSRI-related sexual dysfunction
Practical Considerations
- Start with low doses and titrate slowly to minimize side effects
- Allow 4-6 weeks at therapeutic doses to evaluate efficacy
- If no response after adequate trial (6-8 weeks), consider switching to another augmentation strategy
- Antidepressants may destabilize mood in patients with undiagnosed bipolar disorder, so monitor for emergence of manic symptoms 5
Special Cautions
- Avoid paroxetine and fluoxetine as alternatives to citalopram when using with tamoxifen due to CYP2D6 inhibition 5
- Consider drug interactions: SSRIs with MAOIs are contraindicated (14-day washout period required) 6
- Bupropion can increase the risk of seizures and should be used with caution in patients with factors that lower seizure threshold 2
Remember that while cariprazine has shown promise in some studies of treatment-resistant depression 4, other studies have shown inconsistent results 7, explaining why it might not have worked for this particular patient.