| Antidepressants |
| Amitriptyline |
No |
25–100 mg at bedtime71
|
$10–$33 |
Not recommended over duloxetine or venlafaxine.71 AEs include dry mouth, urinary retention, sedation, vertigo, constipation.184 Monitor BP, heart rate, ECG before and during initiation; weight; mental status.74 Avoid use in patients older than 60 years of age.54
|
| Desipramine |
No |
10–25 mg titrated to 100–150 mg at bedtime91
|
$14–$25 to $115–$160 |
Safer alternative to amitriptyline (less-severe anticholinergic effects, less sedation).60,79,82 Preferred TCA for elderly patients.92 AEs include dry mouth, sedation, dizziness, confusion, orthostatic constipation, urinary retention, blurred vision, weight gain, arrythmias.74 Monitor BP, heart rate, ECG before and during initiation; weight; mental status.74
|
| Duloxetine (Cymbalta) |
Yes |
60 mg/day 62
|
$58 |
First drug approved for treatment of DPN (2004).61 AEs include nausea, somnolence, hyperhidrosis, anorexia, vomiting, constipation, fatigue, dry mouth.184 Monitor BP, mental status, liver enzymes.74 Avoid use in hepatic impairment; avoid use with CrCl < 30 mL/min.144
|
| Venlafaxine |
No |
75–225 mg/day71
|
$14–$26 |
AEs include nausea, somnolence, ECG changes.184 Monitor BP, cholesterol, heart rate.74 May be added to gabapentin for better response.71
|
| Anticonvulsants |
| Carbamazepine |
No |
600 mg/day (200 mg TID) to 800 mg day (200 mg QID)60,91
|
$40–$53 |
AEs include agitation, dry mouth, sedation, ataxia, nausea, vomiting, blurred vision, confusion, fatigue, nystagmus, aplastic anemia (rare).74 Monitor CBC with platelet count, reticulocytes, serum iron, lipid panel, liver function tests, urinalysis, BUN, serum carbamazepine levels, thyroid function tests, serum sodium, ophthalmic exams (papillary reflexes); observe patient for excessive sedation.74
|
| Gabapentin |
No |
900–3,600 mg/day in three divided doses71,184
|
$3–$13 |
AEs include dizziness, somnolence, diarrhea, fatigue, GI upset, peripheral edema.144,184 Monitor serum levels of concomitant antiepileptic therapy.74 Reduce dosage if GFR < 60 mL/min.112
|
| Pregabalin (Lyrica) |
Yes |
150 mg/day (50 mg TID) to 300 mg/day (100 mg TID) 94
|
$519 (brand) |
Second agent approved for treatment of DPN (2004).97 AEs include somnolence, dizziness, peripheral edema, weight gain.184 Monitor degree of sedation, symptoms of myopathy or ocular disturbance, weight gain/edema, creatine phosphokinase, skin integrity (in diabetic patients).74 Treatment may lead to physical or psychological dependence.94,103,104
|
| Valproate sodium |
No |
500–1,200 mg/day in two or three divided doses71
|
$4–$10 |
AEs include elevated liver enzymes, nausea.184 Monitor liver enzymes, CBC with platelet count.74
|
| Opioids |
| Morphine sulfate (MS Contin) |
No |
15–30 mg every 12 to 24 hours 144
|
Every 12 hours: $188–$356 Every 24 hours: $94–$178 (brand) |
Typical opioid effects should be expected (e.g., constipation, somnolence, dizziness, nausea, vomiting, itchiness).144,184 Chronic use may lead to tolerance, frequent dose escalation, and hyperalgesia.71,132,133 Data are insufficient to recommend this drug over oxycodone, dextromethorphan, or tramadol.71
|
| Oxycodone CR (OxyContin) |
No |
Maximum dosage: 120 mg/day in two divided doses of CR formulation71
|
$876 (brand) |
Typical opioid effects should be expected (e.g., constipation, somnolence, dizziness, nausea, vomiting, itchiness).144,184 Chronic use may lead to tolerance, frequent dose escalation, and hyperalgesia.71,132,133 Data are insufficient to recommend this drug over dextromethorphan, morphine sulfate, or tramadol.71
|
| Opioid-Like Analgesics |
| Dextromethorphan |
No |
400 mg/day in four divided doses71,184
|
$126 |
Dissociative anesthetic with powerful psychedelic effects at high doses.158 Primary AE is sedation (at recommended doses).184 Data are insufficient to recommend this drug over oxycodone, morphine sulfate, or tramadol.71
|
| Tapentadol (Nucynta ER) |
Yes |
50–250 mg BID |
$309–$935 (brand) |
Third agent approved for DPN treatment (2012).145 AEs include nausea, dizziness, somnolence, constipation, vomiting, headache.146 Potential for addiction, abuse, misuse; life-threatening respiratory depression; neonatal opioid withdrawal syndrome; interaction with alcohol.146
|
| Tramadol |
No |
210 mg/day in two or four divided doses71,184
|
$96 (for 200-mg dose) |
AEs include nausea, sedation, constipation, headache, dry mouth, urinary retention, confusion, tremor, seizures.74 Monitor respiratory rate, BP, heart rate, signs of tolerance or abuse.74 Data are insufficient to recommend this drug over oxycodone, morphine sulfate, or dextromethorphan.71
|
| Topical Medications |
| Capsaicin (cream) (Trixaicin HP) |
No |
0.075% TID or QID71,144
|
$27 for one 60-g tube (brand) |
May be used as adjunct to oral medications.144 AEs include localized stinging, burning, and itching; coughing; sneezing; rash.74,144,184 Monitor skin breakdown.74
|
| Lidocaine patch (Lidoderm) |
No |
Maximum of three 5% medicated patches applied once for up to 12 hours within a 24-hour period144,169
|
$842 |
May be used as adjunct to oral medications.144 Key AEs include application-site reactions (e.g., blisters, bruising, burning sensation, depigmentation, dermatitis, discoloration, edema, erythema, exfoliation).144,169
|
