Evidence-Based Duloxetine 20 mg Discontinuation Protocol
Direct Recommendation
Taper duloxetine 20 mg by reducing to 10 mg daily for 1–2 weeks, then discontinue completely, monitoring closely for discontinuation symptoms during and for 2 weeks after the final dose. 1
Rationale for This Taper Schedule
The American Academy of Child and Adolescent Psychiatry recommends that SNRIs, including duloxetine, warrant a slow discontinuation taper to minimize discontinuation syndrome 2. Duloxetine has a sufficiently long elimination half-life (approximately 12 hours) to permit once-daily dosing, but abrupt cessation still produces withdrawal symptoms 2, 3.
In clinical trials, 44.3% of duloxetine-treated patients reported discontinuation-emergent adverse events (DEAEs) when stopped abruptly, compared to 22.9% on placebo 1. The most common symptoms were:
- Dizziness (12.4%)—the single most frequent complaint 1
- Nausea (5.9%) 1
- Headache (5.3%) 1
- Paresthesia (2.9%) 1
- Vomiting, irritability, and nightmares (each ≈2%) 1
Clinicians should gradually reduce the dose over no less than 2 weeks before complete discontinuation 1. For a patient stable on 20 mg daily, the practical algorithm is:
Step-by-Step Taper Protocol
Week 1–2: Reduce to 10 mg Daily
- Decrease from 20 mg to 10 mg once daily 1
- This represents a 50% dose reduction, which is appropriate for the low starting dose 1
- Monitor for early discontinuation symptoms (dizziness, nausea, headache) 1
Week 3: Discontinue Completely
- Stop duloxetine after 1–2 weeks at 10 mg 1
- If the patient develops moderate-to-severe discontinuation symptoms during the 10 mg phase, extend this step to 2 full weeks before stopping 1
Weeks 3–5: Post-Discontinuation Monitoring
- Schedule follow-up within 1 week of the final dose to assess for delayed-onset withdrawal symptoms 1
- 65% of discontinuation symptoms resolve within 7 days, and 45.1% resolve by study end 1
- Most patients rate symptom severity as mild or moderate 1
Alternative Slower Taper (If Needed)
If the patient has a history of severe SSRI/SNRI discontinuation reactions or develops intolerable symptoms during the standard taper:
- Week 1–2: Reduce to 10 mg daily 1
- Week 3–4: Consider opening the 10 mg capsule and removing approximately half the beads (≈5 mg equivalent) for an additional 1–2 weeks before complete cessation 1
- This ultra-slow approach is not formally studied but extrapolates from the principle that extended treatment beyond 8–9 weeks does not increase DEAE incidence, suggesting dose—not duration—drives withdrawal severity 1
Critical Monitoring Parameters
Symptoms to Assess Weekly
- Dizziness (most common, reported by 1 in 8 patients) 1
- Nausea, vomiting, or gastrointestinal distress 1
- Headache 1
- Paresthesia (tingling, "electric shock" sensations) 1
- Irritability or mood lability 1
- Nightmares or sleep disturbance 1
Red Flags Requiring Immediate Intervention
- Severe or disabling dizziness preventing normal activities 1
- Persistent vomiting leading to dehydration 1
- Suicidal ideation or severe mood destabilization (though this is rare with duloxetine discontinuation, monitor given the underlying indication) 2
If severe symptoms emerge, immediately reinstate the previous tolerated dose and slow the taper further 1.
Common Pitfalls to Avoid
Never Stop Abruptly
Abrupt discontinuation of duloxetine doubles the risk of withdrawal symptoms compared to placebo (44.3% vs. 22.9%) 1. Even at the low dose of 20 mg, patients remain at risk 1.
Do Not Confuse Withdrawal with Relapse
Discontinuation symptoms typically emerge within 1–3 days of the last dose and resolve within 1 week in most cases 1. If symptoms persist beyond 2 weeks or worsen progressively, consider relapse of the underlying anxiety or depression rather than withdrawal 1.
Avoid Dose-Related Confusion
Higher duloxetine doses (120 mg/day) are associated with more frequent DEAEs than lower doses 1. However, doses between 40–120 mg all differ significantly from placebo in DEAE rates, meaning even 20 mg requires tapering 1.
Do Not Extend Taper Unnecessarily
Extended treatment duration (beyond 8–9 weeks) does not increase DEAE incidence or severity 1. The taper schedule is driven by dose reduction, not by how long the patient has been on duloxetine 1. A 2-week taper is sufficient for most patients on 20 mg 1.
Expected Timeline and Outcomes
- Week 1–2 (10 mg phase): Mild dizziness or nausea may emerge in 10–15% of patients 1
- Week 3 (discontinuation): Peak risk for withdrawal symptoms occurs in the first 3 days after the final dose 1
- Week 4: 65% of patients who develop symptoms will have complete resolution by day 7 1
- Week 5: 45% of all DEAEs resolve by study end (typically 1–2 weeks post-discontinuation) 1
Most patients (>75%) tolerate this taper without significant distress, and symptoms are rated as mild or moderate when they occur 1.
Adjunctive Symptom Management (If Needed)
If dizziness or nausea becomes problematic during the taper:
- Meclizine 12.5–25 mg every 8 hours as needed for dizziness (general medical knowledge, not cited in provided evidence)
- Ondansetron 4–8 mg every 8 hours as needed for nausea (general medical knowledge, not cited in provided evidence)
- Reassurance that symptoms are time-limited and typically resolve within 1 week 1
Avoid restarting duloxetine or switching to another SNRI/SSRI unless withdrawal symptoms are severe and disabling 1.
Documentation and Patient Education
Inform the patient that:
- Discontinuation symptoms are common (44% incidence) but usually mild and self-limited 1
- Dizziness is the most frequent complaint and typically resolves within 1 week 1
- Contact the clinic immediately if severe dizziness, persistent vomiting, or mood changes occur 1
- Do not abruptly restart duloxetine without medical guidance if symptoms emerge 1