eMedicine Specialties > Physical Medicine and Rehabilitation > Peripheral Neuropathy
Diabetic Neuropathy: Treatment & Medication
Updated: Oct 19, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Rehabilitation Program
Physical Therapy
Physical therapy may be a useful adjunct to other therapy, especially when muscular pain and weakness are a manifestation of the patient's neuropathy. The physical therapist can instruct the patient in a general exercise program to maintain his or her mobility and strength.
The patient also should be educated on independent pain management and relaxation strategies to assist with pain control. Transcutaneous electrical nerve stimulation (TENS) may be a recommended modality for patients with neuropathic pain, and the physical therapist can be helpful in teaching and monitoring the patient in its use. In a 1999 case report, Somers and Somers found that application of TENS to the skin of the lumbar region was an effective treatment for the pain of diabetic neuropathy, but there are no controlled studies to confirm this finding.6
In cases of foot ulcers, physical therapy may be indicated for wound care. Treatments may consist of whirlpool, Unna boots (if necessary, although not commonly used), and debridement.
For patients with autonomic neuropathy, balance training and fall prevention education is paramount.
An aquatic therapist can also be helpful.
Brace assessment and orthotic or prosthetic training is useful when appropriate.
Walking aid assessment and implementation may be necessary.
Occupational Therapy
Occupational therapy may be necessary in cases where there is severe loss of functional status. When the lower limbs are involved only, patients may need home modifications and equipment
When the upper limbs are involved, patients may need more extensive functional restoration and adaptive equipment.
When a person loses a limb because of secondary complications even more intensive functional retraining is required.
Speech Therapy
Involvement of a speech therapist rarely is indicated, but professionals from this discipline can help with patients affected by gastroparesis or dysphagia.
Recreational Therapy
A recreational therapist may help the patient with performance of community activities. Many patients with chronic disease, especially elderly patients, become isolated and are at risk for comorbid conditions such as depression.
Medical Issues/Complications
Important secondary complications of diabetic neuropathy are foot ulcers and leg amputations. When a foot ulcer shows signs of infection (eg, thick yellow drainage, erythema around the wound, fever, necrotic tissue), the patient often fares much better by being admitted to a hospital, having the extent of infection assessed (eg, with MRI), and receiving IV antibiotics and foot debridement (if necessary). Intravenous antibiotics should have broad coverage for aerobic bacteria, and if the foot ulcer is chronic or recurrent, coverage should include anaerobes as well.
Surgical Intervention
Surgery is indicated in the following cases:
- In cases where infection is not controlled in foot ulcers, either an aggressive debridement or an amputation may be necessary if signs of necrosis or infection do not improve with IV antibiotics.7
- In cases of intractable gastroparesis (ie, severe nausea and vomiting, severe weight loss), a jejunostomy may be performed to feed the patient nutrients by bypassing the paralytic stomach.
- When impotence is a continual problem, the patient may pursue the option of a penile prosthesis.
- A Charcot joint occurs when the denervated joint becomes deformed when surrounding bone develops osteoporosis. Treatment consists of bracing, placing the joint in a boot, and if necessary, surgery to correct the deformity.
Consultations
- Physical medicine and rehabilitation physicians provide a functional-based comprehensive evaluation and treatment program for patients with diabetic neuropathy.
- Ulcer management may warrant consultation with a specialist at a wound clinic or perhaps a vascular surgeon.
- Consultation with a neurologist should be recommended for any neuropathy that is not managed quickly by the primary care physician. Additionally, particularly complex cases should be referred for in-depth laboratory testing (often genetic testing).
- A cardiologist should monitor patients who have electrocardiographic abnormalities and/or suggestion of CAN.
- A gastroenterologist can monitor patients with intractable GI problems, such as gastroparesis and diarrhea, as well as in the following instances:
- A question remains relative to the diagnosis.
- The patient does not tolerate first-line medications.
- Even with glycemic control, the patient continues to experience severe neuropathy.
Other Treatment
Most often, further treatment depends on the severity of pain symptoms the patient presents with. Simple injections are typically of no benefit. Some case reports suggest that neuromodulation may be an option in particularly refractory cases.
Many health care professionals have produced testimonials that various unproven treatments such as laser or vibratory stimulator treatments are helpful, but controlled studies are necessary.
Medication
Diabetic neuropathy can be grouped into 3 specific categories (ie, painful peripheral neuropathy, cardiovascular autonomic neuropathy, diabetic enteropathy) to simplify treatment. Based on the category, an appropriate treatment regimen can be implemented.
In painful peripheral neuropathy, the acute phase typically occurs in people with intermediate duration of DM. The condition has an acute onset and has a duration of less than 12 months. This acute phase usually is self-limited.
The first line of therapy for this type of neuropathy is tight glucose control and simple analgesics (eg, nonsteroidal anti-inflammatory drugs [NSAIDs], acetaminophen).8
Chronic painful neuropathy typically occurs in people with intermediate duration of DM. However, in these cases of neuropathic pain, simple analgesics are typically not effective. More often, neuropathic pain requires treatment with off-label medications. The primary approved uses for these medications include antidepressants, anticonvulsants, and antiarrhythmics.
Identifying the type of pain can direct the course of therapy. Dysesthetic pain (refer to symptoms in Clinical) can be relieved with capsaicin cream applied qid. The problem with this cream is that it may cause pain during the initial few applications; patients need to be made aware of this potential effect. Additionally, few patients comply with the frequent dosing, and the cream is messy on socks and shoes. Gabapentin also has been reported to work in the treatment of dysesthetic pain.
The next type of pain is paresthetic pain. Tricyclic antidepressants, such as imipramine and amitriptyline, have been shown to be efficacious in randomized controlled trials. Mexiletine, an orally active local anesthetic agent structurally related to lidocaine, also has been used with fair success in this kind of painful neuropathy. Carbamazepine and selective serotonin reuptake inhibitors (SSRIs) also have been used, but SSRIs seem to work only in patients with depression.
For patients with muscular pain, simple stretching exercises and proper footwear can help relieve pain. Occasionally, muscle relaxants may be of benefit in the first 2 weeks of therapy.
Each type of pain or a combination of pain types should be treated. Reevaluation of the painful neuropathy should be performed every 6 weeks.8 Every effort should be made to taper and eventually to stop therapies. Therapies may need to be reinstated at later dates if symptoms flare up.
The most important treatment is glucose control and achieving a near-euglycemic state. However, this state may be difficult to achieve in elderly patients.
Patients with autonomic dysfunction of the gastrointestinal tract are taught to eat very small meals several times a day. In severe cases, reducing the dietary fiber to near zero may improve symptoms. Medications for gastroparesis are Reglan and erythromycin.
Diabetic diarrhea is a diagnosis of exclusion and can be difficult to control. A high-fiber diet, along with diphenoxylate (Lomotil), loperamide (Imodium), or clonidine, can be helpful. Small bowel stasis contributes to bacterial overgrowth, causing diarrhea. Antibiotic treatment is recommended for a period of 2 weeks. Bacterial overgrowth does not have to be proven; it is prudent to treat the condition empirically. Doxycycline, amoxicillin, metronidazole, and ciprofloxacin are choices for the treatment of diabetic diarrhea secondary to bacterial overgrowth of the small intestine.
In cases of neurogenic bladder, voiding every 3-4 h, combined with bethanechol 10-50 mg tid/qid may relieve symptoms.
Symptomatic orthostatic hypotension can be troubling in patients with diabetic neuropathy. Increasing the patient's salt intake, along with use of compression stockings, may help. If these modalities do not improve symptoms, then fludrocortisone may help.
For diabetic impotence, several modalities may be used for treatment. Despite the choices, it is a very difficult condition to treat. All other causes of impotence must be excluded. Once the diagnosis has been confirmed, then drugs such sildenafil (Viagra) can be used (if not contraindicated in the patient), or older methods such as vacuum devices or intracavernosal papaverine injections may be tried. Referral to a urologist is suggested.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
For use in the acute phase of painful neuropathy, along with glucose control, or for use as first-line therapy of painful peripheral neuropathy.
Ibuprofen (Motrin, Ibuprin)
NSAIDs may help decrease inflammation caused by diabetic neuropathy. They also decrease pain.
Adult
400-800 mg PO q6-8h prn with meals
Pediatric
5-10 mg/kg PO q6-8h prn
Coadministration with aspirin increases risk of inducing serious NSAID-related side effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; GI bleed, especially peptic ulcer disease; advanced renal disease; known severe cardiac disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients who potentially are dehydrated; long-term effects may lead to papillary necrosis of kidney, interstitial nephritis, proteinuria, and, occasionally, nephrotic syndrome
Naproxen (Naprosyn, Anaprox, Naprelan)
For relief of mild-to-moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which results in a decrease of prostaglandin synthesis.
Adult
250-500 mg PO bid prn
Pediatric
Not recommended
Coadministration with aspirin increases risk of inducing serious NSAID-related side effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Pregnancy category D in third trimester; acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia, and renal papillary necrosis may occur; patients with preexisting renal disease or compromised renal perfusion risk acute renal failure; leukopenia occurs rarely, is transient, and usually returns to normal during therapy; persistent leukopenia, granulocytopenia, or thrombocytopenia warrants further evaluation and may require discontinuation of drug
Tricyclic antidepressants (TCAs)
TCAs are effective for paresthetic pain, such as the feeling of pins and needles, electricity, numbness, and achy knifelike shooting pains.
Imipramine (Tofranil)
This is the original TCA used for depression. These agents have been suggested to act by inhibiting reuptake of norepinephrine at synapses in central descending pain modulating pathways located in the brainstem and spinal cord.
Adult
Start at 25 mg PO qhs; can increase up to 150 mg PO qhs
Pediatric
Not recommended
Increases toxicity of sympathomimetic agents such as isoproterenol and epinephrine by potentiating effects and inhibiting antihypertensive effects of clonidine
Documented hypersensitivity; concurrent use of MAOIs; during acute recovery period of myocardial infarction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May impair mental or physical abilities required for performance of potentially hazardous tasks; caution in cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, or receiving thyroid replacement
Amitriptyline (Elavil)
Analgesic for certain chronic and neuropathic pain.
Adult
25 mg PO qhs initially; increase slowly to 100 mg PO qhs
Pediatric
Not recommended
Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase levels; inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram
Documented hypersensitivity; administration of MAOIs in past 14 d; history of seizures, cardiac arrhythmias, glaucoma, or urinary retention
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in cardiac conduction disturbances and history of hyperthyroidism and renal or hepatic impairment; avoid using in elderly patients
Antiepileptic drugs (AEDs)
The use of AEDs for the control of painful peripheral neuropathy has generated great interest as a potential therapy. These drugs have been found to have analgesic effects to neuropathic pain. The pharmacology of these drugs involves blocking channels and inhibiting specific neuronic components.
Gabapentin (Neurontin)
Excellent in treating pain described as dysesthetic, such as burning or pins and needles. Gabapentin should be used after all other first-line measures have been used without relief. This drug is a second-generation anticonvulsant. Gabapentin increases brain GABA levels, binds to the alpha2 -delta subunit of voltage-gated calcium channels, and inhibits branched chain amino acid transferase.
Adult
Administer gradually; not to exceed 3600 mg/d PO in divided doses
Pediatric
Not recommended
Antacids may reduce bioavailability of gabapentin significantly (administer at least 2 h following antacids); may increase norethindrone levels significantly
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in severe renal disease; patients should be advised that the drug may cause dizziness; driving is not recommended until patients become used to the effects of gabapentin
Carbamazepine (Tegretol)
AED used mainly in partial seizures. Can be used in peripheral neuropathy as a third-line agent if all other agents fail to reduce or improve symptoms of diabetic neuropathy.
First-generation anticonvulsant. Slows the recovery rate of voltage-gated Na channels, minor Ca2+ channel antagonist effect, and is related chemically to tricyclic antidepressants.
Adult
100 mg PO bid initially; increase to 400 mg PO bid
Pediatric
Not established; used in children with seizure disorders safely but has not been studied for treatment of peripheral neuropathy in children
Coadministration of phenobarbital, phenytoin, or primidone, or a combination of any 2, produces marked lowering of serum levels; the half-lives of phenytoin, warfarin, doxycycline, and theophylline are shortened significantly; concomitant use of erythromycin, cimetidine, propoxyphene, isoniazid, or calcium channel blockers has been reported to result in elevated plasma levels, resulting in toxicity in some cases; reliability of oral contraceptives in preventing pregnancy may be affected
Documented hypersensitivity; history of previous bone marrow depression
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Warn patient about dizziness and hazards of driving or operating heavy machinery; patients should be made aware of potential hematologic problems; any fever, sore throat, ulcers in mouth, easy bruising, or petechial or purpuric hemorrhage should be reported immediately to a physician or patient should go to an emergency department for further evaluation; physicians should obtain complete blood counts prior to administration of the drug
Pregabalin (Lyrica)
FDA approved for the treatment of pain due to generalized diabetic peripheral neuropathy. Excellent in treating pain described as dysesthetic, such as burning or pins and needles. Pregabalin may be considered as a first-line agent in diabetic peripheral neuropathic pain. This drug is also a second-generation anticonvulsant. Pregabalin binds to the alpha-2-delta subunit of voltage-gated calcium channels and inhibits branched chain amino acid transferase. This reduces inappropriate calcium influx into a hypersensitized cell.
Adult
150 mg PO bid
Pediatric
Not established
May cause additive effects on cognitive and gross motor functioning when coadministered with drugs that cause dizziness or somnolence
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Discontinue gradually (over a minimum of 1 wk) to minimize increased seizure frequency in patients with seizure disorders; may cause insomnia, nausea, headache, or diarrhea with abrupt withdrawal; common adverse effects include dizziness, somnolence, blurred vision, weight gain, and peripheral edema; may elevate creatinine kinase level, decrease platelet count, and increase PR interval; doses >300 mg/d associated with higher rate of adverse effects and treatment discontinuation; decrease dose with renal impairment (ie, CrCl <60 mL/min)
Selective serotonin reuptake inhibitors (SSRIs)
Duloxetine became the first medication of any kind to be approved specifically for the treatment of diabetic neuropathy.
Serotoninergic antidepressants have had mixed reviews in the literature. Paroxetine and citalopram are reported to relieve painful sensory symptoms. Fluoxetine was found to relieve symptoms only in depressed patients.
In a review of 6 trials (2220 patients) on duloxetine's effects on painful diabetic peripheral neuropathy (3 trials) and fibromyalgia (3 trials), Lunn et al concluded that 60 mg of duloxetine daily can relieve the pain of peripheral neuropathy in the short-term, calculating a 1.65 risk ratio for a 50% pain reduction at 12 weeks.9 Adverse events were common and dose dependent, according to the authors, but serious ones were rare.
Duloxetine (Cymbalta)
Combination SSRI and norepinephrine reuptake inhibitor is approved specifically for the treatment of diabetic neuropathy–related pain.
Adult
30 mg PO qd initially; increase to 60 mg/d
Pediatric
Not established
Metabolized by CYP1A2 and CY2D6; coadministration with drugs that inhibit AYP1A2 may increase duloxetine blood levels
Documented hypersensitivity; concurrent administration with MAOIs or administration within 14 d of discontinuing an MAOI; uncontrolled narrow-angle glaucoma; end-stage renal disease (requiring dialysis) or severe renal impairment (creatinine clearance <30 mL/min) or any hepatic insufficiency
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Exacerbations of mania may occur; suicidal ideation reported in adolescents;
associated with mean increases in blood pressure averaging 2 mm Hg systolic and 0.5 mm Hg diastolic (measure blood pressure prior to initiating treatment and periodically measure throughout treatment; most commonly observed adverse events include nausea, somnolence, dizziness, constipation, dry mouth, increased sweating, decreased appetite, and asthenia
Abrupt discontinuation, may cause serious adverse events (gradual reduction in dose rather than abrupt cessation recommended when possible)
Paroxetine (Paxil)
SSRI that can be used in second-line or third-line treatment of painful diabetic neuropathy; good for patients who already are depressed.
Adult
20 mg PO qd initially; can increase to doses used for depression, if necessary
Pediatric
Not established
Inhibits CYP2D6, thus may increase toxicity of 2D6 substrates (eg, phenothiazines, propafenone, flecainide and encainide, other SSRIs, tricyclic antidepressants); phenobarbital and phenytoin decrease effects of paroxetine; alcohol, cimetidine, sertraline, phenothiazines, and warfarin increase toxicity of paroxetine; serotonin syndrome (ie, myoclonus, rigidity, confusion, nausea, hyperthermia, autonomic instability, coma, eventual death) occurs with simultaneous use of other serotonergic agents (eg, anorectic agents, tramadol, buspirone, trazodone, clomipramine, nefazodone, tryptophan), discontinue other serotonergic agents at least 2 wk prior to using other SSRIs
Documented hypersensitivity; concurrent administration with MAOIs or administration within 14 d of discontinuing an MAOI
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Exacerbations of mania may occur; hyponatremia has been reported but improves once drug is discontinued; abnormal bleeding also reported, including ecchymoses and purpura; withdrawal reactions can occur (watch for suicidal ideation)
Citalopram (Celexa)
One of the newest antidepressants can be used as a second- or third-line therapy in neuropathy resulting from paresthesia.
Adult
20-40 mg PO qd
Pediatric
Not established
May be potentiated by azole antifungals, omeprazole, and macrolides; serotonin syndrome may be induced by buspirone, tramadol, MAOI, and nefazodone
Documented hypersensitivity; coadministration with MAOIs
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in DM and breastfeeding; cirrhosis, suicidal tendencies, and SIADH; common adverse effects include fatigue and sexual dysfunction
Antiarrhythmic agents
Mexiletine and lidocaine have been used in this drug class. Some intractable neuropathic pain states have been shown to improve with administration of these agents.
Mexiletine (Mexitil)
An orally active local anesthetic drug structurally related to lidocaine. May operate by reducing spontaneous discharges from damaged primary small nerve fibers; recommended only in intractable cases; can be used for both dysesthetic and paresthetic pain.
Adult
225-675 mg/d PO
Pediatric
Not established
Medications that decrease mexiletine levels include aluminum-magnesium hydroxide compounds, atropine, narcotics, hydantoin, rifampin, and urinary acidifiers; metoclopramide and urinary alkalinizers may increase mexiletine levels; cimetidine can either increase or decrease mexiletine levels; may increase caffeine and theophylline levels
Documented hypersensitivity; cardiogenic shock; second- or third-degree AV block (without a pacemaker)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Can be cautiously used in patients who have pacemakers and second- or third-degree block, in those with first-degree AV block, sinus node dysfunction, intraventricular conduction abnormalities, hypotension, or congestive heart failure (consult a cardiologist before using this medication in any of these medical conditions); liver injury reported, particularly in conjunction with congestive heart failure or cardiac ischemia; monitor liver enzymes; rarely leukopenia or agranulocytosis has been seen; CBC should be monitored; convulsions have occurred in about 0.2% of patients on this medication, thus, caution is indicated if there is history of seizures; avoid other drugs that significantly modify the pH of urine
Synthetic adrenocortical steroids
Florinef is used in severely symptomatic orthostatic hypotension. Use if salt tablets and pressure stockings fail to alleviate hypotension.
Fludrocortisone acetate (Florinef)
Used to increase standing blood pressure. Acts to increase sodium retention and expand plasma volume.
Adult
0.05 mg PO bid initially; increase to 0.1 mg PO bid
Pediatric
Not recommended
Antagonizes effects of anticholinergics; rifampin, hydantoin, and barbiturates decrease effects of fludrocortisone; decreases salicylate levels
Documented hypersensitivity; systemic fungal infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Taper dose gradually when therapy is discontinued; caution in Addison disease, potassium loss, and sodium retention
Prokinetic agents
Erythromycin, cisapride, and metoclopramide are used to treat diabetic gastroparesis. Additionally, MiraLAX (polyethylene glycol 3350) is gaining increasing popularity as the first-line agent for severe constipation and lower motor unit bowel.
A newer agent, tegaserod (Zelnorm), may be helpful in patients with chronic ileus. Tegaserod was temporarily withdrawn from the US market in March 2007; however, as of July 27, 2007, restricted use of tegaserod is now permitted via a treatment IND protocol. The treatment IND will allow tegaserod treatment of irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) in women younger than 55 years who meet specific guidelines. Its use is further restricted to those in critical need who have no known or preexisting heart disease.
Earlier this year, tegaserod marketing was suspended because of a meta-analysis of safety data pooled from 29 clinical trials that involved more than 18,000 patients. The results showed an excess number of serious cardiovascular adverse events, including angina, myocardial infarction, and stroke, in those taking tegaserod compared with placebo. In each study, patients were assigned at random to either tegaserod or placebo. Tegaserod was taken by 11,614 patients, and placebo was taken by 7,031 patients. The average age of patients in these studies was 43 years, and most patients (ie, 88%) were women. Serious and life-threatening cardiovascular adverse effects occurred in 13 patients (0.1%) treated with tegaserod; among these, 4 patients had a heart attack (1 died), 6 had unstable angina, and 3 had a stroke. Among the patients taking placebo, only 1 (0.01%) had symptoms suggesting the beginning of a stroke that went away without complication. For more information, see the FDA MedWatch Product Safety Alert.
Erythromycin (E-Mycin, Erythrocin, Ery-Tab, EES)
Macrolide antibiotic that duplicates the action of motilin, which is responsible for the migrating motor complex activity. Binds to and activates motilin receptors. IV administration of this drug enhances the emptying rate of both liquids and solids. Effect can be seen with PO erythromycin. Substitution of the enteric-coated form may be tolerated better by the patient.
Adult
250 mg PO 30 min ac initially
Pediatric
Not established; weight-based dosing recommended; consult a gastroenterologist
Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin increases risk of rhabdomyolysis
Documented hypersensitivity; hepatic impairment
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI side effects are common (administer pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur
Cisapride (Propulsid)
Available for gastroparesis via a limited access treatment IND. Facilitates release of acetylcholine from the myenteric plexus. Increases postprandial/postantral motility and appears to normalize fasting and fed gastric motor patterns.
Adult
10-20 mg PO 30 min ac and hs
Pediatric
Not recommended
Ketoconazole inhibits metabolism of cisapride; can result in prolongation of QT interval on ECG; can accelerate gastric emptying and, therefore, reduce the absorption of certain drugs
Documented hypersensitivity; renal failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May induce arrhythmias; potential benefits should be weighed against risks prior to administration of cisapride to patients with conditions associated with QT prolongation and uncorrected electrolyte disturbances; gastroparesis may be responsible for poor diabetic control in some patients; exogenously administered insulin may begin to act before food has left the stomach and can lead to hypoglycemia because the action of the prokinetic influences the delivery of food to the intestines and, thus, the rate of absorption; insulin dosage or timing of dosage may require adjustment
Metoclopramide (Reglan, Maxolon, Clopra)
Dopamine antagonist that stimulates acetylcholine release in the myenteric plexus. Acts centrally on chemoreceptor triggers in the floor of the fourth ventricle, which provides important antiemetic activity; side effects and tachyphylaxis are problems.
Adult
10-30 mg PO 1 h ac and hs
Pediatric
>6 years: 0.1 mg/kg PO 1 h ac
6-14 years: 2.5-5 mg PO 1 h ac
>14 years: Administer as in adults
Antagonized by narcotics and by anticholinergic drugs; absorption of drugs may be diminished, whereas the rate and/or extent of absorption of drugs from small bowel may be increased
Documented hypersensitivity; gastric hemorrhage; mechanical obstruction; perforation; pheochromocytoma (may cause hypertensive crisis); epilepsy; coadministration with other drugs that are likely to cause extrapyramidal reactions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Gastroparesis may be responsible for poor diabetic control in some patients; exogenously administered insulin may begin to act before food has left the stomach and lead to hypoglycemia; because the action of prokinetic effects influences the delivery of food to intestines and, thus, the rate of absorption, insulin dosage or timing of dosage may require adjustment
More on Diabetic Neuropathy |
| Overview: Diabetic Neuropathy |
| Differential Diagnoses & Workup: Diabetic Neuropathy |
 Treatment & Medication: Diabetic Neuropathy |
| Follow-up: Diabetic Neuropathy |
| References |
| Further Reading |
| « Previous Page | Next Page » |
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Further Reading
Clinical guidelines:
American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Microvascular complications. American Association of Clinical Endocrinologists - Medical Specialty Society
American College of Endocrinology - Medical Specialty Society. 2000 Jan (revised 2007). 6 pages. NGC:005857
Assessment and management of foot ulcers for people with diabetes. Registered Nurses' Association of Ontario - Professional Association. 2005 Mar. 112 pages. NGC:004216
Diabetic foot disorders: a clinical practice guideline. American College of Foot and Ankle Surgeons - Medical Specialty Society. 2000 Sep (revised 2006 Sep). 66 pages. NGC:005270
Diagnosis and treatment of diabetic foot infections. Infectious Diseases Society of America - Medical Specialty Society. 2004 Oct 1. 26 pages. NGC:003874
Practice advisory: utility of surgical decompression for treatment of diabetic neuropathy. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. American Academy of Neurology - Medical Specialty Society. 2006 Jun. 4 pages. NGC:005159
Clinical trials:
A Study for Treatment of Pain in Patients With Diabetic Neuropathy
Efficacy and Safety Study of ARC-4558 for Management of Pain Associated With Painful Diabetic Neuropathy
Study on the Role of Decompression of Lower Extremity Nerves for the Treatment of Patients With Symptomatic Diabetic Neuropathy With Chronic Nerve Compression (DNND)
Thermal Biofeedback for the Treatment of Diabetic Neuropathy
Three Way Interaction Between Gabapentin, Duloxetine, and Donepezil in Patients With Diabetic Neuropathy
Keywords
diabetic neuropathy, neuropathy, peripheral neuropathy, diabetic foot, foot neuropathy, diabetic feet, neuropathy treatment, diabetic peripheral neuropathy, diabetic neuropathy treatment, diabetic neuropathy symptoms, diabetic neuropathic pain, diabetic autonomic neuropathy, diabetes mellitus, dysesthesia, paresthesia, allodynia
