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Metabolic Neuropathy Medication

  • Author: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
Updated: Oct 27, 2014

Medication Summary

See Medical Care for a full discussion of recent and ongoing studies and symptomatic treatment.


Gastrointestinal agents

Class Summary

These agents increase peristalsis of upper GI tract.

Metoclopramide (Clopra, Reglan, Maxolon)


Sensitizes tissue to action of acetylcholine and stimulates motility of upper GI tract; indicated for gastroparesis. In severe gastroparesis, is not absorbed and should be given IV.


Broad-spectrum antibiotics

Class Summary

Therapy must be comprehensive and cover all likely pathogens in the context of neuropathic enteropathy.

Ampicillin (Omnipen, Marcillin, Polycillin, Principen)


Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.

Tetracycline (Sumycin)


Treats gram-positive and gram-negative organisms as well as mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s).

Metronidazole (Flagyl, Protostat)


Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except for Clostridium difficile enterocolitis).


Cholinergic agents

Class Summary

These agents increase peristalsis and secretions in the intestine. They also increase contraction and relaxation of the sphincter of the bladder. They may help in treatment of cystopathy.

Bethanechol (Urecholine, Duvoid, Myotonachol)


Used for selective stimulation of bladder to produce contraction to initiate micturition and empty bladder. Most useful in patients who have bladder hypocontractility, provided they have functional and coordinated sphincters. Rarely used because of difficulty in timing effect and because of GI stimulation.


Tricyclic antidepressants

Class Summary

These agents have been shown to be effective in treating painful diabetic neuropathy. They act on CNS, preventing reuptake of norepinephrine and serotonin at synapses involved in pain inhibition. Benefits are unrelated to relief of depression.

Amitriptyline (Elavil)


Analgesic for certain types of chronic and neuropathic pain.

Nortriptyline (Aventyl HCl, Pamelor)


Has demonstrated effectiveness in treatment of chronic pain. By inhibiting reuptake of serotonin and/or norepinephrine by presynaptic neuronal membrane, this drug increases synaptic concentration of these neurotransmitters in CNS.

Pharmacodynamic effects such as desensitization of adenyl cyclase and down-regulation of beta-adrenergic receptors and serotonin receptors also appear to play roles in its mechanisms of action.


Selective serotonin reuptake inhibitors

Class Summary

These agents specifically inhibit presynaptic reuptake of serotonin but not noradrenaline.

Paroxetine (Paxil)


Effective in painful diabetic neuropathy.



Class Summary

Use of certain anti-epileptic drugs, such as the GABA analogue gabapentin, has proven helpful in some cases of neuropathic pain. Thus, a trial of such an agent might provide analgesia for symptomatic neuropathy.

Phenytoin (Dilantin)


Blocks sodium channels nonspecifically and therefore reduces neuronal excitability in sensitized C-nociceptors. Has been demonstrated effective in neuropathic pain but suppresses insulin secretion and may precipitate hyperosmolar coma in patients with diabetes.

Carbamazepine (Tegretol)


Nonspecific sodium channel blocker that has been effective in treatment of painful diabetic neuropathy; more useful in trigeminal neuralgia.

Gabapentin (Neurontin)


Novel anticonvulsant with unknown mechanism of action; believed to antagonize glutamate excitotoxicity. Has demonstrated effectiveness in neuropathic pain, but doses in clinical trials were as high as 3600 mg.



Class Summary

Recent studies have demonstrated efficacy in different types of neuropathic pain.

Tramadol (Ultram)


Analgesic probably acting over both monoaminergic and opioid mechanisms. Monoaminergic effect shared with TCAs. Tolerance and dependence appear to be uncommon.


Dopamine agonists

Class Summary

In order for a dopamine agonist to offer clinical benefit, it must stimulate D2 receptors. The role of other dopamine receptor subtypes is currently unclear. They inhibit noxious input to spinal cord.

Levodopa (Depar, Larodopa)


Has actions over noradrenergic receptors.


Topical analgesics

Class Summary

Studies have demonstrated efficacy in different types of neuropathic pain. Capsaicin has been shown to have efficacy in treatment of painful diabetic neuropathy and postherpetic neuralgia.

Capsaicin (Dolorac, Zostrix)


Derived from chili peppers; depletes substance P from sensory nerves, causing chemodenervation. Has demonstrated effectiveness in several studies of diabetic neuropathic pain and in other types of neuropathic pain.


Selective serotonin and norepinephrine reuptake inhibitors (SSNRI)

Class Summary

SSNRIs have antidepressant and central pain inhibitory actions.

Duloxetine hydrochloride (Cymbalta)


The efficacy of duloxetine in the treatment of neuropathic pain associated with diabetic peripheral neuropathy was established in 2 large, randomized, placebo-controlled trials in adult patients. These studies led to duloxetine becoming the first FDA-approved agent for the treatment of diabetic neuropathic pain. Action is believed to involve inhibition of central pain mechanisms at the recommended dose of 60 mg/d PO.

Contributor Information and Disclosures

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS Professor Emeritus of Neurology and Psychiatry, Clinical Professor of Medicine, Clinical Professor of Family Medicine, Clinical Professor of Neurosurgery, State University of New York Upstate Medical University; Neuroscience Director, Department of Neurology, Crouse Irving Memorial Hospital

Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS is a member of the following medical societies: American College of International Physicians, American Heart Association, American Stroke Association, American Academy of Neurology, American Academy of Pain Medicine, American College of Forensic Examiners Institute, National Association of Managed Care Physicians, American College of Physicians, Royal College of Physicians, Royal College of Physicians and Surgeons of Canada, Royal College of Surgeons of England, Royal Society of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Glenn Lopate, MD Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Consulting Staff, Department of Neurology, Barnes-Jewish Hospital

Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD, MHA, CPE Founding Editor-in-Chief, eMedicine Neurology; Founder and CEO/CMO, PHLT Consultants; Chief Medical Officer, MeMD Inc

Nicholas Lorenzo, MD, MHA, CPE is a member of the following medical societies: Alpha Omega Alpha, American Association for Physician Leadership, American Academy of Neurology

Disclosure: Nothing to disclose.

Additional Contributors

Milind J Kothari, DO Professor, Department of Neurology, Pennsylvania State University College of Medicine; Consulting Staff, Department of Neurology, Penn State Milton S Hershey Medical Center

Milind J Kothari, DO is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Fernando Dangond, MD, and Luis Carlos Sanin, MD, to the development and writing of this article.

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Table 1. Symptoms and Signs of Peripheral Neuropathy*
Small-Fiber Sensory Large-Fiber Sensory Autonomic
Burning pain Loss of vibration Heart rate changes
Cutaneous allodynia Proprioception loss Postural blood pressure change
Paresthesias Loss of reflexes Abnormal sweating
Lancinating pain Slowed NCVs Gastroparesis
Loss pain/temperature Sensory ataxia Impotence
Foot ulcers Weakness Abnormal ejaculation
Visceral pain loss    
* Modified from Apfel, 1999.[14]
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