What is Cymbalta (duloxetine) used for and what are its side effects?

Cymbalta (Duloxetine): Clinical Uses and Side Effects

FDA-Approved Indications

Cymbalta (duloxetine) is FDA-approved for major depressive disorder, generalized anxiety disorder (adults and children ≥7 years), diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain in adults. 1

Primary Clinical Uses

Neuropathic Pain Conditions

• Duloxetine 60 mg daily is the most effective dose for diabetic peripheral neuropathy, achieving ≥50% pain reduction in significantly more patients than placebo (risk ratio 1.73) with a number needed to treat of 5 2
• For painful diabetic neuropathy specifically, duloxetine demonstrates sustained efficacy up to one year in open-label trials 2
• The American Diabetes Association recommends duloxetine as a first-line medication for neuropathic pain, particularly diabetic peripheral neuropathy 2
• Duloxetine shows more pronounced effectiveness in platinum-based chemotherapy-induced neuropathy compared to taxane-induced neuropathy 3

Chronic Musculoskeletal Pain

• For chronic knee osteoarthritis, duloxetine 60 mg daily is recommended as second-line treatment when topical NSAIDs are insufficient or when multiple joints are affected 3, 2
• Duloxetine demonstrates small to moderate benefits for pain and function at 3-6 months and 6-12 months in knee osteoarthritis 2
• Evidence shows greater effectiveness in older patients (>65 years) and specifically in knee osteoarthritis compared to hip osteoarthritis 2
• For chronic low back pain with insufficient response to exercise and physical therapy, duloxetine provides small improvements and can be considered for patients without contraindications 3

Fibromyalgia

• Duloxetine 60-120 mg daily produces small to moderate improvements in pain, function, and quality of life in fibromyalgia patients 3
• The risk ratio for ≥50% pain reduction at 12 weeks is 1.57 with a number needed to treat of 8 2
• Duloxetine is FDA-approved and recommended as first-line treatment for fibromyalgia 3

Psychiatric Conditions

• Duloxetine is effective for major depressive disorder and generalized anxiety disorder in adults 1, 4
• For patients with co-occurring chronic pain and depression, duloxetine may provide dual benefits as depression can exacerbate physical pain symptoms 3

Dosing and Administration

Standard Dosing Protocol

• Start with 30 mg once daily for one week, then increase to 60 mg once daily to minimize nausea 2
• Maximum effect for pain conditions typically requires 60 mg daily 2
• For pain management, 60 mg once daily appears as effective as 60 mg twice daily 2
• Duloxetine can be taken with or without food 1
• Swallow capsules whole—do not chew, crush, open, or mix contents with food or liquids 1

Special Populations

• In older adults (≥65 years), adverse events may be more severe but can be attenuated with lower doses and slower titration 3, 2
• Unlike tricyclic antidepressants, duloxetine does not produce clinically important electrocardiographic changes or blood pressure alterations, making it safer for older adults 2

Discontinuation

• Duloxetine must be tapered over at least 2-4 weeks for patients treated longer than 3 weeks to avoid withdrawal symptoms 2
• Never stop duloxetine abruptly without consulting the prescribing provider 2

Side Effects

Most Common Adverse Effects

The most frequent side effects include 1:

• Nausea (most common—can be reduced by starting at 30 mg daily) 2
• Dry mouth
• Sleepiness and fatigue
• Constipation
• Loss of appetite
• Increased sweating
• Dizziness

Serious Adverse Effects Requiring Monitoring

Blood pressure changes and falls 1:

• May increase blood pressure—monitor before starting and throughout treatment
• Can cause orthostatic hypotension with dizziness or fainting, especially when initiating or increasing dose
• Increased fall risk, particularly in elderly patients

Liver damage 1:

• Symptoms include itching, right upper abdominal pain, dark urine, jaundice, enlarged liver
• Avoid heavy alcohol use while taking duloxetine as concomitant use may cause severe liver injury 1

Serotonin syndrome (potentially life-threatening) 1:

• Symptoms: agitation, hallucinations, coordination problems, muscle twitching, racing heartbeat, blood pressure changes, fever, nausea, vomiting, diarrhea, muscle rigidity, tremor, seizures
• Risk increased when combined with other serotonergic drugs (SSRIs, SNRIs, MAOIs, triptans, tramadol, fentanyl, amphetamines) 1

Abnormal bleeding 1:

• Increased risk when combined with warfarin, NSAIDs, or aspirin 1

Hyponatremia 1:

• Elderly patients at greater risk
• Symptoms: headache, weakness, unsteadiness, confusion, memory problems

Other serious effects 1:

• Severe skin reactions (blisters, peeling rash, mouth sores)
• Visual problems (eye pain, vision changes, swelling around eyes)
• Seizures or convulsions
• Urinary retention (decreased flow or inability to urinate)
• Manic episodes

Discontinuation Symptoms

Stopping duloxetine too quickly causes withdrawal symptoms in up to one-third of patients 1:

• Anxiety and irritability
• Fatigue and sleep problems
• Headache
• Sweating and dizziness
• Electric shock-like sensations
• Nausea, vomiting, diarrhea

Pediatric Considerations

In children and adolescents 1:

• Most common side effects: nausea, decreased weight, dizziness
• Height and weight should be monitored during treatment
• Adult side effects may also occur

Important Drug Interactions

Avoid or use with extreme caution 1:

• MAOIs (contraindicated)
• Thioridazine (can cause serious heart rhythm problems or sudden death)
• Potent CYP1A2 inhibitors (ciprofloxacin, enoxacin)
• Other serotonergic drugs (see serotonin syndrome above)

Use with caution 1:

• Drugs metabolized by CYP2D6, especially those with narrow therapeutic index
• Blood thinners (warfarin)
• NSAIDs and aspirin

Clinical Considerations

Diabetes-Specific Warning

• In longer-term studies, duloxetine caused a small increase in A1C compared to placebo in patients with diabetes 3, 2

Pregnancy and Breastfeeding

• Notify healthcare provider immediately if pregnant or planning pregnancy 1
• Duloxetine passes into breast milk and may harm the baby—discuss feeding options with provider 1

Discontinuation Rate

• Approximately 16% of patients discontinue duloxetine due to adverse effects 5
• Nausea is the most common reason for discontinuation 5
• Most adverse events are mild to moderate in severity 5