What happens when an adult patient with a history of depression, anxiety, or chronic pain stops taking duloxetine (serotonin-norepinephrine reuptake inhibitor, SNRI)?

Discontinuation Syndrome When Stopping Duloxetine

When you stop duloxetine, you will likely experience withdrawal symptoms including dizziness, nausea, headache, irritability, and paresthesias—these occur in approximately 44% of patients who discontinue abruptly, compared to 23% with placebo. 1, 2

What Happens During Discontinuation

Common Withdrawal Symptoms

The FDA-approved drug label and clinical trials identify specific discontinuation-emergent adverse events that occur significantly more often than placebo 1, 2:

• Dizziness (12.4% of patients) - the most frequently reported symptom 2
• Nausea (5.9%) 2
• Headache (5.3%) 2
• Paresthesias (2.9%) - electric shock-like sensations 1, 2
• Irritability (2.4%) 2
• Vomiting (2.4%) 2
• Insomnia 1
• Anxiety 1
• Hyperhidrosis (excessive sweating) 1
• Fatigue 1

Additional Severe Symptoms

Beyond the common symptoms, the FDA label warns of more concerning manifestations 1:

• Dysphoric mood and emotional lability 1
• Agitation and confusion 1
• Sensory disturbances beyond simple paresthesias 1
• Lethargy 1
• Hypomania 1
• Tinnitus 1
• Seizures (rare but reported) 1

Timeline and Severity

Duration of Symptoms

• 65% of withdrawal symptoms resolve within 7 days of onset 2
• 45.1% of all discontinuation symptoms had resolved by study endpoint 2
• Most patients rate symptom severity as mild to moderate 2
• Symptoms are generally self-limiting but some cases can be severe 1

Dose-Related Risk

• Higher doses (120 mg/day) are associated with more frequent discontinuation symptoms compared to lower doses 2
• All doses between 40-120 mg/day show significantly higher discontinuation symptoms than placebo 2
• Extended treatment duration beyond 8-9 weeks does not increase the incidence or severity of withdrawal symptoms 2

How to Safely Discontinue Duloxetine

Mandatory Tapering Protocol

The FDA label and clinical guidelines mandate gradual dose reduction over at least 2 weeks whenever possible 3, 4, 1:

• Standard taper: reduce dose gradually over 2-4 weeks minimum 3, 4, 1
• Older adults: use slower tapering with at least one week at each dose level 3
• If intolerable symptoms occur during taper, resume the previous dose and decrease more gradually 1

When Rapid Discontinuation Is Necessary

If duloxetine must be stopped quickly due to adverse effects 4:

• A more rapid taper may be necessary but requires closer monitoring 4
• Consider whether another medication needs to be substituted, given duloxetine's multiple indications (depression, anxiety, pain) 4

Critical Pitfall to Avoid

Never stop duloxetine abruptly 3, 1. The ASCO guideline specifically states: "When patients stop duloxetine, it should be tapered slowly, as stopping abruptly can lead to withdrawal symptoms" 3. This is emphasized across multiple high-quality guidelines and the FDA label 3, 1.

Special Considerations

Treatment Duration Matters

• Tapering is especially important after treatment longer than 3 weeks 4
• The discontinuation syndrome risk underscores the importance of careful patient selection (limited to clinically significant chronic pain or depression) 3

Comparison to Other Antidepressants

While duloxetine's discontinuation profile is similar to other SNRIs and SSRIs 2, it differs from fluoxetine, which has a longer half-life and causes relatively rare and mild withdrawal symptoms 5. Duloxetine's approximately 12-hour elimination half-life 6 makes it more prone to withdrawal symptoms than longer-acting agents.

Monitoring During Discontinuation

Patients should be monitored for 1:

• All symptoms listed above
• Emergence of depressive symptoms
• Return of pain symptoms (if used for chronic pain)
• Blood pressure changes (duloxetine can affect BP) 1