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Peripheral Neuropathy

Part of A Practical Guide to HIV Drug Side Effects

2006

Peripheral Neuropathy (peripheral = furthest away; neuro = nerve; pathy = damage)

Peripheral neuropathy (PN) -- nerve damage that causes numbness, burning, tingling and sometimes severe pain in the toes, feet and legs, and sometimes in the hands and arms -- is most often caused by the "d" drugs:

  • d4T (Zerit)
  • ddC (Hivid)
  • ddI (Videx EC)

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Other drugs, such as the following, can also cause this complication:

  • Flagyl (metronidazole)
  • thalidomide
  • isoniazid
  • vincristine
  • dapsone

Less commonly, PN can also stem from the nucleoside analogue 3TC (alone in Epivir and in the combination drugs Combivir and Trizivir).

Other factors can cause or contribute to PN as well, such as:

  • HIV itself
  • diabetes
  • cancer treatment
  • alcohol
  • cocaine
  • amphetamines

Let your doctor know right away if you have symptoms of PN. When possible, it is extremely important that the drug(s) causing PN be stopped immediately because delaying this may result in permanent problems. When causative medicines are stopped shortly after symptoms begin, the pain and numbness usually subside over time and are eventually completely eliminated, although that may take several months. However, failure to immediately stop using the problematic drugs may greatly reduce the chances for complete reversal of symptoms. Too many people have ended up with permanent pain, numbness and burning because symptoms weren't quickly reported to their doctors or because the doctors hesitated to take them off the drugs.


Tips for Handling Peripheral Neuropathy

Large trials with diabetics, small studies with PHAs, and many anecdotal reports from PHAs have shown the usefulness of the following nutrient supplements for preventing or reversing PN:

  • alpha-lipoic acid (in doses of 300-500 mg, 2-3 times per day; preferably using an extended-release form)
  • gamma-linolenic acid (in doses of 240 mg, twice per day)
  • acetyl-L-carnitine (in doses of 1,000 mg, 3 times per day)

A British study showed that PHAs on the "d" drugs (ddC, d4T, ddI) have low levels of acetyl-L-carnitine, and that 18 months of supplementation improved both symptoms and nerve biopsy results, even when the "d" drugs were continued.

Also important is replenishment of magnesium, often deficient in PHAs (try 500 mg daily) and B complex vitamins, in particular, the following:

  • vitamin B12 (1,000 mcg, 2-7 times per week; nasal gel or injections may work better than pills because of absorption problems)
  • vitamin B6 (25-50 mg daily), taken with a B complex supplement, since deficiencies of these B vitamins can cause neuropathy and are common in PHAs

In addition, the nutrient protocol proposed by Dutch researchers to help address nucleoside-analogue-caused mitochondrial dysfunction may help (see "Body Distortions").

Anything you do that soothes and reduces pressure on hypersensitive feet or hands can help. This includes:

  • limiting walking distances
  • wearing loose-fitting shoes and socks
  • avoiding standing for lengthy periods
  • avoiding repetitive pressure on the hands
  • soaking your feet or hands in ice water on a regular basis
  • raising your heels or hands off the mattress with a small pillow can help prevent increased pain while sleeping
  • keeping heavy covers off of painful areas
  • regular exercise may help by increasing circulation to the nerves
  • many swear by acupuncture or acupressure, with improvement often occurring with the first treatment, although repeated treatments may be necessary for long-term relief

The following pharmaceutical agents help some reduce pain, although they won't eliminate numbness:

  • Neurontin (gabapentin) is usually the first-line therapy since it often works better for neuropathic pain than other possible meds.
  • For pain that mostly occurs at night -- the standard recommendation is for oral amitriptyline (Elavil, a tricyclic antidepressant), beginning with low doses in order to minimize certain side effects (dry mouth, sedation, urinary retention and low blood pressure upon suddenly sitting up or getting out of bed -- orthostatic hypotension). A starting dose of 25 mg at bedtime is gradually increased to 75 mg (or as high as 100-150 mg if needed). Elavil may be particularly useful when sleep problems accompany the neuropathy because it has sedative effects.
  • For predominantly daytime pain -- oral nortriptyline (Pamelor) is often advised since it is less sedating, also beginning with a low dose of 10 mg per day, and gradually increasing to 30 mg, 3 times daily.

With these drugs, effective reduction of pain may not occur for up to two or three weeks, so patience is required. When one of these is not effective, another may still be.

  • For occasional pain, standard anti-inflammatories such as ibuprofen (Motrin, Advil) may help with mild neuropathic symptoms.
  • For more severe pain, the World Health Organization (WHO) steps for treatment of pain should be used to ensure proper treatment (see below). When pain is under-treated or not treated, it may greatly increase the risk that it will become permanent.

WHO's four-step approach to drug treatment of HIV-related pain:
In general, medications should be given in the maximum tolerated doses before moving up to the next step. Where there is chronic pain, it is thought best to treat around the clock in order to prevent pain. If necessary, the usual meds can be augmented by short-acting drugs in order to treat breakthrough pain. With all these drugs, individual responses may vary and will be the best guide for proper med use.

  • Step 1: Try acetaminophen or a non-steroidal anti-inflammatory drug (NSAID). Most effective for mild pain. Possibilities include: ibuprofen, aspirin and naproxen. When one NSAID doesn't work, another might. Long-term use can cause gastrointestinal bleeding and should be avoided, if possible. People with low platelets, kidney dysfunction or low serum albumin levels (common in those with wasting) should not take NSAIDs. Those with gastric Kaposi's sarcoma should take them with an antacid or avoid them.
  • Step 2: If NSAIDs are not enough, a weak opiate derivative might help, either alone or along with a Step 1 agent. Possibilities include codeine alone, codeine with acetominophen (Tylenol), hydrocodone with acetaminophen, or oxycodone with acetaminophen.
  • Step 3: If the above are inadequate, talk to your doctor about switching to a stronger opiate such as hydromorphone, transdermal fentanyl patches, levorphanol, morphine sulfate (intravenous), sustained-release morphine sulfate (oral) or meperidine. The minimum daily dose that affords pain relief should be used.
  • Step 4: At any point during the preceding steps, consider adding adjuvant therapies to boost the effectiveness of the other drugs. At the top of this list, due to good effectiveness with few side effects, is the antiseizure med gabapentine (Neurontin). Other boosters include antihistamines like hydroxyzine (Vistaril); butyrophenones like haloperidol (Haldol) and pimozide (Orap); psychostimulants like methylphenidate (Ritalin), dextroamphetamine (Dexedrine) and pemoline (Cylert); amine precursors like tryptophan; selective serotonin re-uptake inhibitors such as fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft); and heterocyclic and non-cyclic antidepressants like trazadone (Desyrel) and maprotiline (Ludiomil).




  
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This article was provided by Canadian AIDS Treatment Information Exchange. Visit CATIE's Web site to find out more about their activities, publications and services.
 
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Neurological Complications of AIDS Fact Sheet
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