eMedicine Specialties > Neurology > Neuromuscular Diseases
Metabolic Neuropathy: Treatment & Medication
Updated: Jul 9, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
The best medical care for patients with metabolic neuropathy is control of the underlying metabolic condition, which results in better control of the neuropathy.- Diabetic neuropathy: No pharmacologic treatment exists for moderately severe to severe diabetic peripheral neuropathy or other metabolic neuropathies. Only symptomatic treatments exist for pain and other conditions such as gastroparesis. However, control of hyperglycemia has been demonstrated to decrease progression of diabetic neuropathy. This section discusses recent and ongoing studies, followed by a discussion of symptomatic treatment.
- Insulin pump: Continuous infusion of insulin has been demonstrated to improve results of NCS. This treatment seems to benefit only patients with mild peripheral neuropathy associated with diabetes. Exercise caution to prevent severe hypoglycemic episodes.
- Aldose reductase inhibitors: Recent meta-analysis of randomized controlled trials of aldose reductase inhibitors indicates that benefits of treatment have not been demonstrated conclusively in diabetic neuropathy.
- Neurotrophic factors: Neurotrophic factors have been tested in animal models of diabetic neuropathy. Insulin growth factor (IGF) and NGF have yielded encouraging results in animal studies. However, in humans, only recombinant NGF has been tested in phase II clinical trials, and the initial results did not demonstrate major benefits.
- Gangliosides: Gangliosides have been shown to promote improvement in sensation without changes in NCVs. A moratorium has been placed on their development because of significant adverse effects.
- Linoleic acid: In patients with diabetes, conversion of linolic acid or its metabolite gamma linoleic acid (GLA) is impaired. A recent multicenter study using GLA for 1 year demonstrated clinical and neurophysiologic improvement.
- Advanced glycosylation end products (AGE): AGE inhibitors have shown some value in treatment of peripheral neuropathy in rats. Human trials are pending.
- Human intravenous immunoglobulin: Small open-label studies have demonstrated improvement in diabetic peripheral neuropathy, especially in neuropathies with asymmetric involvement (eg, diabetic lumbosacral radiculoplexopathy) with intravenous immunoglobulin. Further studies are necessary to draw definitive conclusions.
- Symptomatic treatment of diabetic neuropathy
- Gastroparesis: The first step is to attempt multiple small feedings. The amount of dietary fat should be decreased. Metoclopramide, which sensitizes tissue to the action of acetylcholine, stimulates the motility of the upper gastrointestinal tract. Cisapride, a prokinetic drug, is effective in some patients. If medications fail, jejunostomy may help.
- Enteropathy: Stasis of bowel contents with bacterial overgrowth may contribute to diarrhea. Treatment with broad-spectrum antibiotics such as ampicillin or tetracycline is the initial therapy. Metronidazole may also be given. Anticholinergics may help in controlling diarrhea. Patients with poor digestion may benefit from a gluten-free diet.
- Cystopathy: Patients with neurogenic bladder may not perceive when the bladder is full. Manual downward pressure of the bladder can help. Parasympathomimetic agents such as bethanechol also may be of help.
- Treatment of painful neuropathy: The FDA has approved duloxetine hydrochloride, a selective serotonin and norepinephrine reuptake inhibitor (SSNRI), for the treatment of diabetic peripheral neuropathic pain. A recent study concerning neuropathic pain using the NNT approach (number of patients needed to treat to get a beneficial response) was published recently by Sindrup and Jensen.9 This section reviews the drugs most often used to treat pain in peripheral neuropathies based on their approach.
- Tricyclic antidepressants: Tricyclic antidepressants have been shown to be effective in treating painful diabetic neuropathy. Tricyclics act on the central nervous system, preventing the reuptake of norepinephrine and serotonin at synapses involved in pain inhibition. Benefits are unrelated to relief of depression. Amitriptyline and nortriptyline are used most commonly.
- Selective antidepressants: Selective serotonin reuptake inhibitors (SSRIs) specifically inhibit presynaptic reuptake of serotonin but not noradrenaline. Paroxetine has been effective in painful diabetic neuropathy.
- Ion channel blockers
- Lidocaine: Lidocaine is a nonspecific sodium channel blocker. It relieves painful diabetic neuropathy in severe cases but is not convenient to administer since no oral form is available.
- Mexiletine: Mexiletine is an oral analogue of lidocaine. It has been used at a dosage of 10 mg/kg, but clinical trials so far have shown equivocal results.
- Phenytoin: Phenytoin blocks sodium channels nonspecifically and therefore reduces neuronal excitability in sensitized C-nociceptors. It has been demonstrated to be effective in neuropathic pain, but it suppresses insulin secretion and may precipitate hyperosmolar coma in patients with diabetes.
- Carbamazepine: Carbamazepine is another nonspecific sodium channel blocker that has been effective in the treatment of painful diabetic neuropathy, but it is more useful in trigeminal neuralgia.
- Gabapentin: Gabapentin is a novel anticonvulsant with an unknown mechanism of action, but it is believed to antagonize glutamate excitotoxicity. It has demonstrated effectiveness in neuropathic pain, but doses in clinical trials were as high as 3600 mg. Freeman et al performed a meta-analysis of 7 randomized, placebo-controlled trials that evaluated the efficacy and safety of pregabalin treatment of painful diabetic peripheral neuropathy.10 Daily doses included 150, 300, and 600 mg/d, with dosing intervals of 2 or 3 times per day. Pregabalin was found to be effective for painful diabetic peripheral neuropathy at all doses and intervals, with the greatest and most rapid pain reduction seen in patients receiving pregabalin 600 mg/d divided into 2 or 3 doses.
- Lamotrigine: Lamotrigine is a new anticonvulsant acting as a stabilizer in the slow inactivated conformation of a subtype of sodium channels, indirectly suppressing the neuronal release of glutamate. Studies in trigeminal neuralgia favor its use, but no studies have been reported in other neuropathic pain syndromes.
- N -methyl-D-aspartate (NMDA) antagonists: Aspartate, an excitatory neurotransmitter, has been shown to play a role in the development of neuropathic pain. Its receptor is NMDA. NMDA antagonists have shown effectiveness when given intravenously for neuropathic pain (eg, ketamine). Other studies with another NMDA antagonist, dextromethorphan, have shown efficacy for neuropathic pain.
- Opioids: Until recently, high controversy surrounded opioid use in neuropathic pain. However, recent studies have demonstrated its efficacy in different types of neuropathic pain. Tramadol is an analgesic drug probably acting over both monoaminergic and opioid mechanisms. The monoaminergic effect is shared with tricyclic antidepressants. Tolerance and dependence appear to be uncommon. Doses of 100-400 mg have been shown to be effective in diabetic neuropathic pain. Oxycodone and morphine have been tried in other neuropathic pain syndromes with good results. Risk of dependence remains an issue to consider, and these agents should not be given to individuals at risk of addiction.
- Levodopa: Dopamine agonists inhibit noxious input to the spinal cord. Levodopa also has actions over noradrenergic receptors. One recent study showed benefit in polyneuropathic pain with 300 mg/d of levodopa.
- Capsaicin: Capsaicin is an alkaloid substance derived from chilies. It depletes substance P from sensory nerves, causing chemodenervation. It has demonstrated effectiveness in several studies of diabetic neuropathic pain and in other types of neuropathic pain as well. It must be applied topically every 4 hours over the entire pain area. It causes a burning sensation, and applying it with gloves is advisable.
- Miscellaneous: Several still unproven medical treatments are proposed for mitochondrial respiratory chain disorders, including drugs such as coenzyme Q10, menadione, vitamin E, ascorbic acid, N -acetylcysteine, riboflavin, succinate, L-carnitine, and dichloroacetate.
Surgical Care
- Surgical release of entrapment neuropathy (CTS, ulnar neuropathy at the elbow, TTS)
- Specialized surgical care of diabetic foot and foot ulcers, including vascular and plastic surgery evaluation
- Jejunostomy for severe gastroparesis
- Pancreatic islet transplants have been reported to improve diabetic neuropathy and pancreas-kidney transplantation in patients with diabetes and renal failure
- Liver transplantation (may improve familial amyloid neuropathy)
- Renal transplantation (may improve uremic neuropathy)
Consultations
- Nutrition or genetics consults, especially for patients with diabetes or metabolic neuropathies in childhood
- General surgery for patients in whom transplant is considered
- Plastic or vascular surgery for patients with diabetic foot ulceration or necrosis
Diet
- Low-calorie diet in patients with diabetes
- Modified lipid-intake diets for inherited conditions associated with alteration in lipid metabolism
- Low-protein intake in chronic renal failure and in hepatic failure
Activity
No restrictions in activity are recommended for most of the metabolic neuropathies. However, some neuropathies in childhood can be triggered by exercise.
Medication
See Medical Care for a full discussion of recent and ongoing studies and symptomatic treatment.
Gastrointestinal agents
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.
Adult
10 mg PO qd ac
5-20 mg IV bid prn
Pediatric
<6 years: 0.1 mg/kg PO
6-14 years: 2.5-5 mg PO
>14 years: 10 mg PO
Anticholinergics may decrease efficacy; opiate analgesics may increase toxicity in CNS
Documented hypersensitivity; pheochromocytoma; GI hemorrhage, obstruction, or perforation; history of seizure disorders
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in history of mental illness or Parkinson disease
Broad-spectrum antibiotics
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.
Adult
250 mg PO q8h
Pediatric
<7 days, <2000 g: 50 mg/kg/d IV/IM divided bid (q12h)
<7 days, >2000 g: 75 mg/kg/d IV/IM divided tid (q8h)
>7 days, <1200 g: 50 mg/kg/d IV/IM divided bid (q12h)
>7 days, 1200-2000 g: 75 mg/kg/d IV/IM divided tid (q8h)
>7 days, >2000 g: 100 mg/kg/d divided qid (q6h)
Infants/children: 100-200 mg/kg/d IV/IM divided q4-6h; not to exceed 2-3 g/d
Probenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction
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).
Adult
250 mg PO q8h
Pediatric
>8 years: 25-50 mg/kg PO divided q6h; not to exceed 3 g/d
Antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate decrease availability; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risks during pregnancy; can increase hypoprothrombinemic effects of anticoagulants
Documented hypersensitivity; severe hepatic dysfunction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; if used during tooth development (last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines
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).
Adult
500 mg PO q6h
Pediatric
<7 days, >1200 g: 7.5-15 mg/kg PO/IV qd or divided q12h (bid)
>7 days, >1200 g: 15-30 mg/kg PO/IV qd divided q12h (bid)
Infants and children: 30 mg/kg PO/IV qd divided q6h (qid); not to exceed 4 g/d
May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity; disulfiram reaction may occur with orally ingested ethanol
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy
Cholinergic agents
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.
Adult
5-10 mg PO initially; not to exceed 50 mg; total dose should continue at 6-h intervals
Pediatric
Not established
Ganglion-blocking compounds may cause drop of blood pressure to critical levels
Documented hypersensitivity; peptic ulcer disease, obstructive pulmonary disease, bradycardia, vasomotor instability, hypotension, atrioventricular conduction defects, hyperthyroidism, epilepsy, mechanically obstructed GI or GU tract
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
Urinary retention secondary to possible reflux of urine into kidneys may occur
Tricyclic antidepressants
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.
Adult
10-25 mg PO hs initial, gradually increase to 50-100 mg
Pediatric
<9 years: Not established
9-12 years: 1-3 mg/kg PO qd divided q8h; not to exceed 200 mg/d
>12 years: 25-100 mg PO qd divided qd/tid; not to exceed 200 mg/d
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; 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, renal or hepatic impairment; avoid using in elderly; adverse effects include blurred vision, constipation, sleepiness, dry mouth, and dysautonomia
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.
Adult
10-25 mg PO hs initial, gradually increase to 50-100 mg
Pediatric
<6 years: Not established
6-7 years: 10 mg PO qhs
7-11 years: 10-20 mg PO qhs
>11 years: 25-35 mg PO qhs
Cimetidine may increase levels; may increase PT in patients stabilized with warfarin
Documented hypersensitivity; narrow-angle glaucoma; MAOIs in past 14 d
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Adverse effects include blurred vision, constipation, sleepiness, dry mouth, and dysautonomia; caution in cardiac conduction disturbances and history of hyperthyroidism, renal or hepatic impairment; because of pronounced effects in cardiovascular system, best to avoid in elderly
Selective serotonin reuptake inhibitors
These agents specifically inhibit presynaptic reuptake of serotonin but not noradrenaline.
Paroxetine (Paxil)
Effective in painful diabetic neuropathy.
Adult
10-60 mg PO qd
Pediatric
<8 years: Not established
>8 years: 10-30 mg PO qd; start with 5-10 mg PO qd and advance gradually by 5 mg/d qwk
Triptans (5-HT1 agonists), buspirone, or lithium may increase risk of serotonin syndrome; may inhibit hepatic metabolism into active form of hydrocodone; may inhibit hepatic metabolism of flecainide and increase risk of toxicity
Documented hypersensitivity; history of seizures; MAOIs in past 14 days; impaired liver or renal function; elderly subjects; suicidal thoughts
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
Patients may be advised not to operate heavy machinery or perform tasks that may imply high risk of personal injury during early stages of treatment, as it may cause excessive somnolence, blurred vision, and asthenia in some patients
Anticonvulsants
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.
Adult
300 mg PO qhs
Pediatric
Infants/children: 5-10 mg/kg/d PO/IV divided bid/tid
Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase toxicity
Barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate may decrease effects
May decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, valproic acid
Documented hypersensitivity; sino-atrial block; second- and third-degree AV block; sinus bradycardia; Adams-Stokes syndrome
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Perform blood counts and urinalyses when therapy is begun and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if skin rash appears and do not resume use if rash is exfoliative, bullous, or purpuric; rapid IV infusion may result in death from cardiac arrest, marked by QRS widening; caution in acute intermittent porphyria and diabetes (may elevate blood glucose); discontinue use if hepatic dysfunction occurs
Carbamazepine (Tegretol)
Nonspecific sodium channel blocker that has been effective in treatment of painful diabetic neuropathy; more useful in trigeminal neuralgia.
Adult
400-1000 mg PO bid
Pediatric
<6 years: Not established
>6 years: 10 mg/kg PO qd
Serum levels may increase significantly within 30 d of danazol coadministration (avoid whenever possible); do not coadminister with MAOIs; cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; may decrease primidone and phenobarbital levels (their coadministration may increase carbamazepine levels)
Documented hypersensitivity; history of bone marrow depression; MAOIs within last 14 d
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Do not use to relieve minor aches or pains; caution with increased intraocular pressure; obtain CBC and serum iron baseline prior to treatment, during first 2 months, and yearly or every other year thereafter to monitor for aplastic anemia; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness
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.
Adult
300 mg/d PO initial; gradually increase; mean dose is 2400 mg/d
Pediatric
Not established
Antacids may significantly reduce bioavailability (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; adverse effects include somnolence, dizziness, and diarrhea
Analgesics
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.
Adult
100-400 mg PO qd shown to be effective in diabetic neuropathic pain
Pediatric
Not established
Decreases carbamazepine effects significantly; cimetidine increases toxicity; antidepressants increase risk of serotonin syndrome
Documented hypersensitivity; opioid dependency; MAOIs within 14 days; use of SSRIs, TCAs, opioids; acute alcohol intoxication
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 cause dizziness, nausea, constipation, sweating, pruritus; additive sedation with alcohol and TCAs; abrupt discontinuation can precipitate opioid withdrawal symptoms; adjust dose in liver disease, myxedema, hypothyroidism, hypoadrenalism; pregnancy, breastfeeding; seizure; development of tolerance or dependency with extended use
Dopamine agonists
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.
Adult
300 mg/d PO shown recently to benefit in polyneuropathic pain
Pediatric
Not established
Phenothiazines, hydantoins, pyridoxine, and hypotensive agents may decrease effects; MAOIs may cause hypertensive reactions
Documented hypersensitivity; narrow-angle glaucoma; MAOI therapy; melanomas or undiagnosed skin lesions
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
Common adverse effects include nausea, vomiting, hypertension, dyskinesias, and postural hypotension; caution in arrhythmias, asthma, wide-angle glaucoma, myocardial infarction, peptic ulcer disease
Topical analgesics
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.
Adult
0.075% preparation applied topically q4h over entire pain area
Also available in 0.025% preparation
Pediatric
Not established
None reported
Documented hypersensitivity; broken or irritated skin
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
Main adverse effects are burning and/or stinging sensations at site of application, particularly first wk of therapy
For external use only; avoid contact with eyes; do not use tight bandage; discontinue use if condition worsens or symptoms persist for 14-28 d
Selective serotonin and norepinephrine reuptake inhibitors (SSNRI)
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.
Adult
60 mg PO qd (120 mg PO qd is also considered safe and effective, but somewhat less tolerated)
Pediatric
Not established; drug package insert contains warning of risk of suicidality in children receiving antidepressants; anyone considering use of Cymbalta in this population must balance risk with clinical need
Metabolized by CYP1A2 and CYP2D6; coadministration with drugs that inhibit CYP1A2 (eg, fluvoxamine, cimetidine, ciprofloxacin, enoxacin) may increase duloxetine blood levels and toxicity; coadministration with drugs that inhibit CYP2D6 (eg, paroxetine, fluoxetine, quinidine) may increase duloxetine blood levels and toxicity; duloxetine moderately inhibits CYP2D6 and may decrease elimination of CYP2D6 substrates (eg, tricyclic antidepressants, phenothiazines [eg, thioridazine], type 1C antiarrhythmics [eg, propafenone, flecainide]); coadministration with MAO inhibitors may cause serious, sometimes fatal reactions that include hyperthermia, rigidity, myoclonus, autonomic instability, mental status changes including extreme agitation, delirium, and coma (see Contraindications)
Documented hypersensitivity; uncontrolled narrow-angle glaucoma; within 14 d of stopping MAO inhibitor use (do not initiate MAO inhibitors within 5 d of stopping duloxetine)
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
Observe closely for clinical worsening and suicidality when initiating treatment or following dosage change; gradually decrease dose when discontinuing, do not abruptly discontinue; caution with hepatic impairment or end-stage renal disease; recommended not to prescribe to patients with substantial alcohol use or evidence of chronic liver disease; may cause slight blood pressure increase; may activate mania or hypomania; common adverse effects include nausea, dry mouth, constipation, decreased appetite, fatigue, somnolence, and increased sweating
More on Metabolic Neuropathy |
| Overview: Metabolic Neuropathy |
| Differential Diagnoses & Workup: Metabolic Neuropathy |
 Treatment & Medication: Metabolic Neuropathy |
| Follow-up: Metabolic Neuropathy |
| References |
| « Previous Page | Next Page » |
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Further Reading
Keywords
metabolic neuropathy, peripheral nerve disorder, systemic disease neuropathy, diabetic neuropathy, uremic neuropathy, adrenal disease–associated neuropathy, thyroid neuropathy, hepatic disease–associated neuropathy, POEMS, monoclonal gammopathies, monoclonal gammopathy of unknown significance, MGUS, myelin-associated glycoprotein–associated gammopathy, MAG, amyloid neuropathy, porphyric neuropathy
