Duloxetine Dosing for Nerve Pain
Start duloxetine at 30 mg once daily for 1 week, then increase to the target dose of 60 mg once daily for neuropathic pain. 1
Starting Dose and Titration Strategy
Begin with 30 mg once daily for the first week to minimize nausea, which is the most common adverse effect, then advance to 60 mg once daily. 2, 1
The 1-week lead-in period at 30 mg significantly reduces gastrointestinal side effects compared to starting directly at 60 mg. 2, 3
For patients with tolerability concerns or those with diabetes complicated by renal disease, consider maintaining the lower 30 mg starting dose for a longer period before escalating. 1
Target Therapeutic Dose
The evidence-based target dose is 60 mg once daily, which has demonstrated consistent efficacy in painful diabetic peripheral neuropathy with pain relief occurring within 1 week of reaching this dose. 2, 4, 3, 5
Duloxetine 60 mg once daily is as effective as 60 mg twice daily, making once-daily dosing the preferred regimen. 2
The number needed to treat (NNT) for 50% pain reduction at 12 weeks is 5 for diabetic neuropathy, indicating substantial clinical benefit. 4, 6
Maximum Dose Considerations
Do not routinely exceed 60 mg daily for neuropathic pain—there is no evidence that higher doses (120 mg) provide additional pain relief, and they are clearly less well tolerated with higher adverse event rates. 1, 4, 5
If considering dose escalation beyond 60 mg in non-responders, increase in 30 mg increments, though this approach lacks supporting efficacy data. 1
Duration of Adequate Trial
- Allow sufficient time for therapeutic assessment—pain relief can begin within 1 week at 60 mg, but a full trial should extend to at least 12 weeks before declaring treatment failure. 4, 3
Special Population Adjustments
Avoid duloxetine entirely in patients with severe renal impairment (GFR <30 mL/min) or chronic liver disease/cirrhosis. 1
For patients with moderate renal impairment or diabetes complicated by renal disease, use a lower starting dose and titrate more gradually. 1
Critical Pitfalls to Avoid
Never discontinue duloxetine abruptly—taper gradually to prevent withdrawal symptoms including dizziness, headache, nausea, paresthesia, and irritability. 1
Do not start duloxetine at 60 mg in an attempt to achieve faster pain relief, as this significantly increases early discontinuation due to nausea and other gastrointestinal side effects. 2, 3
Do not combine with MAO inhibitors—allow at least 14 days after stopping an MAOI before starting duloxetine, and at least 5 days after stopping duloxetine before starting an MAOI. 1
Recognize that duloxetine's evidence base is strongest for diabetic peripheral neuropathy; efficacy in other neuropathic pain conditions is less well established. 2
Monitoring and Adverse Effects
Expect minor adverse effects in most patients, with nausea being most common, but serious adverse events are rare (occurring in <1% of patients). 4, 6
Approximately 16% of patients discontinue duloxetine due to adverse effects, most commonly nausea, dizziness, and somnolence. 4, 6
Duloxetine does not produce clinically significant electrocardiographic changes or blood pressure alterations, and routine aminotransferase monitoring is unnecessary. 2