What is the best non-stimulant to add to citalopram (Celexa) and nortriptyline?

Best Non-Stimulant to Add to Citalopram and Nortriptyline

Bupropion is the best non-stimulant to add to your current regimen of citalopram and nortriptyline, as it provides complementary noradrenergic and dopaminergic activity without increasing serotonergic burden or anticholinergic side effects. 1

Primary Recommendation: Bupropion

• Bupropion (Wellbutrin) should be started at 37.5 mg every morning, increased by 37.5 mg every 3 days, up to a maximum of 150 mg twice daily 1
• This agent is activating and may provide rapid improvement in energy levels, which is particularly useful if apathy or fatigue are prominent symptoms 1
• Give the second dose before 3 PM to minimize insomnia risk 1
• Bupropion is contraindicated in patients with seizure disorders or significant agitation 1

Why Bupropion Works Best in This Context

• You are already on two serotonergic agents (citalopram and nortriptyline), which increases your risk of serotonin syndrome if another serotonergic drug is added 1
• Combining multiple serotonergic medications requires extreme caution, with monitoring especially critical in the first 24-48 hours after dosage changes 1
• Bupropion works through norepinephrine and dopamine reuptake inhibition, providing a different mechanism without compounding serotonergic effects 1
• Nortriptyline already provides noradrenergic activity, but bupropion's dopaminergic effects offer unique benefits for motivation and concentration 1

Alternative Option: Buspirone

If anxiety is a prominent feature alongside depression:

• Buspirone can be added at 20-30 mg/day for augmentation of existing antidepressant therapy 2
• In patients failing to respond to SSRIs (including citalopram), 59% showed complete or partial remission when buspirone was added 2
• 79% of initial responders who remained on buspirone augmentation for at least 4 months were symptom-free at follow-up 2
• Buspirone has minimal drug interactions with your current regimen and no serious side effects were observed in combination therapy 2

Critical Safety Considerations

Serotonin Syndrome Risk

• You are currently on two medications that increase serotonin (citalopram as an SSRI and nortriptyline as a TCA) 1
• Symptoms of serotonin syndrome include mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 1
• These symptoms can arise within 24-48 hours after combining medications or increasing doses 1
• Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness, which can be fatal 1

Cardiac Monitoring

• Citalopram can cause QT prolongation at doses exceeding 40 mg/day and should be avoided in patients with long QT syndrome 1
• Nortriptyline also affects cardiac conduction, so ECG monitoring is prudent, especially if you're over 40 years old 3

Anticholinergic Burden

• Nortriptyline has anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision) 3
• Avoid adding medications with additional anticholinergic properties, as this increases risk of confusion, falls, and cognitive impairment 1, 3

What NOT to Add

Avoid Additional Tricyclic Antidepressants

• Never combine nortriptyline with amitriptyline or other TCAs, as nortriptyline is already the active metabolite of amitriptyline 4
• This combination is pharmacologically redundant and increases cardiac toxicity and anticholinergic side effects without additional benefit 4

Avoid Additional SSRIs

• Adding another SSRI to citalopram would be redundant and significantly increase serotonin syndrome risk 1

Avoid MAOIs

• Monoamine oxidase inhibitors are absolutely contraindicated with your current regimen due to severe serotonin syndrome risk 1

Monitoring After Addition

• Assess treatment response after 2-4 weeks at therapeutic doses 3
• Monitor for new or worsening side effects, particularly in the first 24-48 hours after starting or increasing doses 1
• Watch for signs of serotonin syndrome if any serotonergic agent is added 1
• Consider ECG monitoring given the combination of citalopram and nortriptyline 1, 3

If Inadequate Response Persists

• If partial response occurs, consider switching strategies rather than continuing to add medications 5
• After two failed antidepressant trials, switching to a third monotherapy resulted in remission rates below 20% in clinical trials 5
• Consider consultation with psychiatry for more complex augmentation strategies or alternative approaches 5