Can a Patient Be on Celexa, Wellbutrin, and Abilify Together?
Yes, a patient can safely be on Celexa (citalopram), Wellbutrin (bupropion), and Abilify (aripiprazole) concurrently, as this combination is used in clinical practice for treatment-resistant depression, though careful monitoring for serotonin syndrome and seizure risk is essential.
Rationale for This Combination
Evidence Supporting Combined Use
Aripiprazole as adjunctive therapy has demonstrated efficacy when added to antidepressants for treatment-resistant major depressive disorder, including combinations with both SSRIs and bupropion 1, 2.
In a 52-week open-label study, patients receiving aripiprazole adjunctive to bupropion showed mean CGI-S improvement of -1.4, with 40.4% completing the full treatment course 2.
A separate study specifically examined aripiprazole added to bupropion-resistant depression and found rapid improvement in depressive symptoms with low-dose aripiprazole (2.5-10 mg/day), with effects sustained for at least 4 months 1.
The combination of aripiprazole with SSRIs (like citalopram/escitalopram) has also been studied, with a 62.5% response rate and 50% remission rate in psychotic major depression when aripiprazole was combined with escitalopram 3.
Critical Safety Considerations
Serotonin Syndrome Risk
The primary concern is serotonin syndrome when combining two serotonergic agents (Celexa and potentially Wellbutrin).
Serotonin syndrome can arise within 24-48 hours after combining serotonergic medications, characterized by mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 4.
When combining non-MAOI serotonergic drugs, start the second agent at a low dose, increase slowly, and monitor closely for symptoms, especially in the first 24-48 hours after dosage changes 4.
Citalopram is noted to have the least effect on CYP450 isoenzymes compared with other SSRIs, potentially reducing drug interaction risk 4.
Seizure Risk Management
Bupropion lowers the seizure threshold, with an estimated risk of 0.4% at recommended doses, and this risk may be additive when combined with other medications.
Bupropion should not be used in agitated patients or those with seizure disorders, and the second dose should be given before 3 p.m. to minimize insomnia risk 4.
While aripiprazole is less likely to cause seizures compared to other antipsychotics, caution is still warranted 5.
Maximum bupropion dosing should not exceed 150 mg twice daily when used in combination therapy to minimize seizure risk 4.
QT Prolongation Monitoring
Citalopram may cause QT prolongation associated with Torsade de Pointes at daily doses exceeding 40 mg/day and should be avoided in patients with long QT syndrome 4.
Obtain a baseline ECG before initiating this combination, particularly if citalopram doses approach 40 mg/day.
Practical Dosing Strategy
Initiation Approach
Start with one antidepressant first (either citalopram 10 mg daily or bupropion 37.5 mg daily), establish tolerability for 1-2 weeks 4.
Add the second antidepressant at low dose, monitoring closely for 24-48 hours for serotonin syndrome symptoms 4.
Add aripiprazole last at 2.5-5 mg daily once antidepressant combination is stable 1, 2.
Monitoring Parameters
Weekly assessment for first month focusing on: akathisia, extrapyramidal symptoms, activation/agitation, sleep disturbances, and any signs of serotonin syndrome 4, 2.
Akathisia occurred in 23.6% of patients on SSRI/SNRI plus aripiprazole combinations but often resolved with dose adjustment or propranolol treatment 2, 3.
Monitor fasting glucose and lipids at baseline and periodically, as metabolic effects can occur with aripiprazole (mean weight gain +2.4 to +3.1 kg at 52 weeks) 2.
Common Pitfalls to Avoid
Do not combine with MAOIs: Both bupropion and citalopram are contraindicated with monoamine oxidase inhibitors 4.
Avoid rapid titration: Increase doses gradually at 1-2 week intervals for shorter half-life SSRIs like citalopram 4.
Do not exceed citalopram 40 mg/day due to QT prolongation risk 4.
Watch for discontinuation syndrome: If stopping citalopram, taper over 10-14 days to limit withdrawal symptoms including dizziness, paresthesias, and anxiety 4.
Consider sexual dysfunction: Baseline sexual functioning should be assessed, as SSRIs commonly cause sexual side effects, though some improvement may occur with aripiprazole addition 2.