What can be used to augment citalopram (Celexa)?

Augmentation Strategies for Citalopram

Bupropion is the preferred agent to augment citalopram, demonstrating superior efficacy in reducing depression severity compared to buspirone, with lower discontinuation rates due to adverse events. 1

Primary Augmentation Agent: Bupropion

• Bupropion decreases depression severity more effectively than buspirone when used to augment citalopram treatment 1
• Discontinuation due to adverse events is lower with bupropion compared to buspirone as augmentation therapy 1
• Bupropion functions as a norepinephrine and dopamine reuptake inhibitor, providing a complementary mechanism to citalopram's serotonergic action 1
• The medication does not cause significant cardiovascular effects, making it safer for patients with cardiac concerns 1

Bupropion Dosing and Safety Considerations

• Start at 37.5 mg every morning, then increase by 37.5 mg every 3 days as tolerated 2
• Maximum dose is 150 mg twice daily 2
• Give the second dose before 3 p.m. to minimize insomnia risk 2
• Contraindicated in patients with seizure disorders, brain metastases, or elevated seizure risk (0.1% seizure risk) 2, 1
• Common side effects include disturbed sleep, dry mouth, headaches, and nausea 1
• Particularly activating; avoid in highly agitated patients 2

Alternative Augmentation: Lithium

• Lithium can be used to augment antidepressant drugs when bupropion is contraindicated or ineffective 2
• Initial dosage: 150 mg per day 2
• Target blood levels of 0.2 to 0.6 mEq/L (0.2 to 0.6 mmol/L) are generally adequate, usually achieved with 150 to 300 mg per day 2
• Elderly patients are prone to develop neurotoxicity at higher lithium dosages 2

Buspirone as Secondary Option

• While buspirone can augment citalopram, it is less effective than bupropion for reducing depression severity 1
• Higher discontinuation rates due to adverse events compared to bupropion 1
• May be considered when bupropion is contraindicated due to seizure risk

Critical Drug Interaction Warnings

Absolute Contraindications

• Never combine citalopram with MAOIs (phenelzine, isocarboxazid, moclobemide, isoniazid, linezolid) due to serotonin syndrome risk 2, 3
• Allow appropriate washout periods between medications 2

Cautions with Augmentation

• Monitor for serotonin syndrome when combining any serotonergic agents, especially within the first 24-48 hours after dosage changes 2
• Symptoms include mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 2
• Citalopram maximum dose is 40 mg/day due to QT prolongation risk; reduce to 20 mg/day in patients taking cimetidine or CYP2C19 inhibitors 3

Monitoring During Augmentation

• Assess response after 12 weeks of augmentation therapy at therapeutic doses 2
• If no improvement occurs, revert to monotherapy or explore alternative combinations 2
• Document current symptomatology clearly before initiating augmentation to evaluate benefit 2
• Monitor for increased bleeding risk if patient is taking NSAIDs, aspirin, or warfarin concurrently 3

Special Populations

Depression with Psychosis

• Patients with depression and psychosis require concomitant antipsychotic medication rather than simple antidepressant augmentation 2

Smoking Cessation Comorbidity

• Bupropion provides dual benefit as both depression augmentation and smoking cessation aid 1
• Particularly beneficial for patients with depression who smoke 1