What is the recommended dosage and usage of duloxetine (Cymbalta) for various medical conditions?

Duloxetine Dosing and Usage Recommendations

Diabetic Peripheral Neuropathic Pain

For diabetic peripheral neuropathic pain, start duloxetine at 30 mg once daily for 1 week to minimize nausea, then increase to the target dose of 60 mg once daily. 1

• The FDA-approved dose is 60 mg once daily, with no evidence that higher doses provide additional significant benefit, and higher doses are clearly less well tolerated 1
• This dosing achieves approximately 50% pain reduction in 1 out of every 5-6 patients treated (NNT 5.8) at 12 weeks 2, 3
• The American Diabetes Association recommends duloxetine as one of three first-line pharmacologic treatments (along with pregabalin and gabapentin) for neuropathic pain in diabetes 2
• Pain relief can occur within one week of reaching the 60 mg dose 4
• For patients with renal impairment (common in diabetes), consider a lower starting dose and gradual titration, and avoid use entirely if creatinine clearance is <30 mL/min 1

Fibromyalgia

Begin duloxetine at 30 mg once daily for 1 week, then increase to 60 mg once daily for fibromyalgia. 1

• The FDA-approved dose is 60 mg once daily 1
• Some patients may respond to the 30 mg starting dose and can remain at this lower dose 1
• There is no evidence that doses >60 mg/day provide additional benefit, even in non-responders, and higher doses increase adverse reactions 1
• Efficacy data shows NNT of 8 for 50% pain reduction at 12 weeks and sustained benefit at 28 weeks 2, 5

Chronic Musculoskeletal Pain (Osteoarthritis and Low Back Pain)

For chronic musculoskeletal pain including osteoarthritis and chronic low back pain, start at 30 mg once daily for 1 week, then increase to 60 mg once daily. 1

• The recommended dose is 60 mg once daily 1
• Higher dosages show no additional benefit and are associated with higher rates of adverse reactions 1
• The CDC recommends duloxetine for osteoarthritis pain (particularly in multiple joints or when topical NSAIDs are insufficient) and for chronic low back pain when nonpharmacologic approaches have been inadequate 2
• Duloxetine shows small to moderate benefits for osteoarthritis pain and function, with evidence suggesting greater effectiveness in older patients (>65 years) and those with knee osteoarthritis 2

Neuropathic Pain (General)

Duloxetine 60 mg once daily is a first-line treatment for neuropathic pain, started at 30 mg daily for 1 week before increasing. 2

• The Mayo Clinic Proceedings guidelines recommend duloxetine as one of four first-line medications for neuropathic pain 2
• An adequate trial duration is 4 weeks at the target dose 2
• Maximum dose is 60 mg twice daily (120 mg/day total), though this is rarely more effective than 60 mg once daily 2
• Duloxetine has demonstrated consistent efficacy specifically in painful diabetic peripheral neuropathy, but has not been adequately studied in other neuropathic pain types 2

Chemotherapy-Induced Peripheral Neuropathy

For chemotherapy-induced peripheral neuropathy (CIPN), duloxetine 30 mg daily for 1 week followed by 60 mg daily is recommended. 2, 6

• This is the only pharmacologic intervention with Level I, Grade B evidence for CIPN treatment 2
• Reduction of neuropathic pain is better in cisplatin-treated patients than taxane-treated patients 2

Generalized Anxiety Disorder

For adults <65 years with generalized anxiety disorder, initiate at 60 mg once daily, or start at 30 mg once daily for 1 week before increasing to 60 mg. 1

• For geriatric patients (≥65 years), start at 30 mg once daily for 2 weeks before considering increase to 60 mg daily 1
• For pediatric patients 7-17 years, start at 30 mg once daily for 2 weeks before considering increase to 60 mg once daily 1
• While 120 mg daily has shown effectiveness, there is no evidence that doses >60 mg/day confer additional benefit 1
• If increasing beyond 60 mg, do so in 30 mg increments; maximum studied dose is 120 mg/day 1

Major Depressive Disorder

For major depressive disorder, start at 40 mg/day (20 mg twice daily) to 60 mg/day (once daily or 30 mg twice daily). 1

• Some patients benefit from starting at 30 mg once daily for 1 week before increasing to 60 mg once daily 1
• While 120 mg/day has shown effectiveness, there is no evidence that doses >60 mg/day confer additional benefits 1

Administration Guidelines

Administer duloxetine orally with or without meals; swallow capsules whole without chewing, crushing, or opening. 1

• Do not open capsules and sprinkle contents on food or mix with liquids, as this affects the enteric coating 1
• If a dose is missed, take it as soon as remembered unless it's almost time for the next dose; never take two doses at the same time 1

Common Adverse Effects and Management

Nausea is the most common adverse effect, occurring less frequently when starting at 30 mg daily for 1 week before increasing to 60 mg. 2, 4

• Other common adverse effects include somnolence, dizziness, constipation, dry mouth, and reduced appetite, which are typically mild to moderate and transient 2, 4
• Approximately 16% of patients discontinue duloxetine due to adverse effects 5, 7
• The number needed to harm for withdrawal due to adverse events is 15 3
• Serious adverse events are rare 5, 7
• Monitor blood pressure as duloxetine can cause modest hypertension 6

Contraindications and Special Populations

Avoid duloxetine in patients with chronic liver disease, cirrhosis, or severe renal impairment (GFR <30 mL/min). 1

• Do not use within 14 days of discontinuing an MAOI intended to treat psychiatric disorders 1
• Allow at least 5 days after stopping duloxetine before starting an MAOI 1
• Do not initiate duloxetine in patients receiving linezolid or IV methylene blue due to serotonin syndrome risk 1
• Adverse events may be more severe in older adults but can be attenuated with lower doses and slower titration 2
• Aminotransferase monitoring is unnecessary 2
• Duloxetine does not produce clinically important electrocardiographic changes or blood pressure changes in most patients 2

Discontinuation Protocol

When discontinuing duloxetine, taper the dose gradually rather than stopping abruptly to minimize withdrawal symptoms. 1

• Withdrawal symptoms include dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue 1
• For patients with history of withdrawal symptoms, consider a slower taper over 3-4 weeks with smaller dose decrements (e.g., 120 mg → 100 mg → 80 mg → 60 mg) 6
• Use small increments at intervals of at least one week at each dose level 6

Key Clinical Pearls

• Duloxetine's efficacy in neuropathic pain is independent of its antidepressant activity, with analgesic effects occurring at lower doses and earlier than antidepressant effects 2
• The drug may be particularly useful in patients with comorbid depression, anxiety, or multiple pain conditions given its broad efficacy profile 8
• Reassess pain and quality of life frequently; if substantial pain relief is not achieved (pain remains ≥4/10) after an adequate trial, consider adding or switching to another first-line medication 2
• An adequate trial requires 4 weeks at the target dose for neuropathic pain 2