What is the recommended protocol for switching from citalopram (Celexa) to desvenlafaxine (Pristiq)?

Switching from Citalopram to Desvenlafaxine

Begin tapering citalopram while simultaneously starting desvenlafaxine 50 mg daily, reducing citalopram by 50% for 3-7 days before complete discontinuation. This cross-taper approach minimizes discontinuation symptoms while establishing therapeutic levels of the new medication 1.

Switching Protocol

Week 1: Initiation Phase

• Start desvenlafaxine 50 mg once daily (the FDA-approved therapeutic dose) while maintaining current citalopram dose 1
• Take desvenlafaxine at approximately the same time each day, with or without food 1
• Swallow tablets whole—do not divide, crush, chew, or dissolve 1
• After 2-3 days of overlap, reduce citalopram by 50% (e.g., from 20 mg to 10 mg, or from 40 mg to 20 mg) 2
• Continue this reduced citalopram dose for 3-7 days while maintaining desvenlafaxine 50 mg 2

Week 2: Completion of Taper

• Discontinue citalopram completely after the 3-7 day taper period 2, 1
• Continue desvenlafaxine 50 mg daily 1
• The FDA label explicitly states that "discontinuation symptoms have been reported when switching patients from other antidepressants" and recommends that "tapering of the initial antidepressant may be necessary to minimize discontinuation symptoms" 1

Dosage Considerations for Desvenlafaxine

• Do not exceed 50 mg daily initially—doses above 50 mg show no additional therapeutic benefit but increase adverse effects 1, 3, 4
• The FDA label clearly states that "doses of 50 mg to 400 mg per day were shown to be effective, although no additional benefit was demonstrated at doses greater than 50 mg per day and adverse reactions and discontinuations were more frequent at higher doses" 1
• If dose adjustment is needed for renal or hepatic impairment, maximum dose is 50 mg daily for moderate renal impairment or moderate-to-severe hepatic impairment 1

Monitoring Schedule

First Week Contact

• Contact patient within 3-7 days to assess for discontinuation symptoms from citalopram and tolerability of desvenlafaxine 2
• Monitor specifically for SSRI discontinuation symptoms: dizziness, paresthesias, anxiety, irritability, confusion, headache 1
• Assess for desvenlafaxine adverse effects: nausea (most common), insomnia, nervousness, tremors 2, 5, 3

Ongoing Monitoring

• Assess blood pressure at baseline and periodically during treatment, as desvenlafaxine can cause dose-dependent increases 6, 5
• Monitor for cardiac conduction abnormalities if patient has cardiac disease history 6
• Evaluate therapeutic response at 4-6 weeks after completing the switch 2
• Desvenlafaxine reaches steady-state plasma concentrations within 4-5 days, faster than venlafaxine 3

Critical Safety Warnings

Absolute Contraindications

• Never combine with MAOIs—allow at least 14 days after stopping an MAOI before starting desvenlafaxine, and at least 7 days after stopping desvenlafaxine before starting an MAOI 1
• This applies to both citalopram (which should already be discontinued) and desvenlafaxine 2, 1

Serious Adverse Effects to Monitor

• Hypertension and QTc interval prolongation 5
• Exacerbation of ischemic cardiac disease 5
• Elevated lipids and liver enzymes 5
• Increased risk of behavioral activation and suicide-related events, particularly in younger patients 2

Advantages of This Switch

Pharmacokinetic Benefits

• Desvenlafaxine has minimal CYP450 metabolism (primarily glucuronidation), resulting in significantly fewer drug-drug interactions compared to citalopram 2, 5, 3, 4
• Linear pharmacokinetics with low protein binding simplify dosing 5
• Once-daily dosing improves adherence 3

Clinical Context

• Evidence from the STAR*D trial demonstrates that switching between antidepressants after initial treatment failure shows similar efficacy regardless of which specific agent is chosen 6, 7
• In severely depressed patients (HAM-D >31) who failed SSRI treatment, SNRIs like desvenlafaxine's parent compound venlafaxine showed superior efficacy compared to switching to another SSRI 7
• No additional benefit exists for doses above 50 mg daily, making this the optimal maintenance dose 1, 3, 4

Common Pitfalls to Avoid

• Do not abruptly discontinue citalopram—always taper to minimize discontinuation symptoms 1
• Do not start desvenlafaxine at doses higher than 50 mg—this only increases adverse effects without improving efficacy 1, 3
• Do not use desvenlafaxine 25 mg as a starting dose; this is intended only for gradual dose reduction when discontinuing treatment 1
• Research shows that abrupt discontinuation of desvenlafaxine 50 mg produces equivalent discontinuation symptoms to a 1-week taper, but this applies to stopping desvenlafaxine, not starting it 8