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The major classes of drugs currently used to treat peripheral neuropathy include:

• Antidepressants
• Anticonvulsants
• Antiarrhythmics
• Narcotic analgesics
• Non-narcotic analgesics
• Other drugs
• Topical agents

Antidepressants

Tricyclic Antidepressants

Tricyclic antidepressants (TCAs) are the most widely studied class of drugs regarding treatment for neuropathic pain. Examples include:

• Amitriptyline (Elavil)
• Nortriptylene (Aventyl, Pamelor)
• Desipramine (Norpramine)
• Imipramine (Janimine)

Tricyclic antidepressants work by inhibiting the reuptake (reabsorption) of three neurotransmitters associated with mood: serotonin, norepinephrine and dopamine. They also relieve pain. Tricyclic antidepressants are generally considered effective for spontaneous pain and hyperalgesia (increased sensitivity to pain).

There is evidence that the efficacy of different TCAs is similar but that individuals may respond slightly better to one drug over the others. If patient response is not sufficient with one TCA, the physicians may prescribe a different TCA until one is found that is effective. In studies evaluating the use of these drugs for diabetic neuropathy, approximately one-third of patients achieved a 50% reduction of pain. Efficacy of TCAs does not appear to be related to the quality of the pain (e.g. stabbing, or burning).

Side-effects of TCAs can be strong and their overall tolerability is considered poor although they are widely used. Side-effects may outweigh the benefits especially for older people. Adverse effects may include:

• Dry mouth
• Dizziness
• Constipation
• Drowsiness/sedation
• Muscle twitches
• Weakness
• Nausea
• Weight gain
• Urinary retention
• Cognitive/memory difficulties
• Increased sweating
• Decreased libido (sexual drive)

Tricyclic antidepressants are contraindicated in people with various health conditions including:

• Cardiac arrhythmia (irregular heartbeat)
• Recent heart attack
• Congestive heart failure
• Glaucoma

Selective Serotonin Reuptake Inhibitors

Selective serotonin reuptake inhibitors (SSRIs) are drugs that block the reuptake of the neurotransmitter, serotonin, that is involved in the transmission of nerve impulses. This leaves more serotonin in the brain and improves mood. This class of drugs has also has been found to reduce pain. Clinical trials indicate that they are less effective than TCAs for controlling pain for patients with peripheral neuropathy. For patients who cannot tolerate TCAs, SSRIs may be considered an option.

Examples of SSRI's include:

• Citalopram (Celexa)
• Paroxetine (Paxil)
• Fluoxetine (Prozac)
• Sertraline (Zoloft)

Adverse effects of SSRI's may include:

• Somnolence or insomnia
• Nausea/vomiting
• Dry mouth
• Decreased libido and/or impotence

Atypical Antidepressants

Atypical antidepressants are a class of drugs that work by inhibiting the reuptake of serotonin and norepinephrine and are known as SSNRIs (selective serotonin and norepinephrine reuptake inhibitors). Examples include:

• Duloxetine (Cymbalta) - Approved by the FDA in September 2004, duloxetine (Cymbalta) was the first drug that was specifically approved for the treatment of neuropathic pain associated with diabetic neuropathy. The most common side-effects reported by patients included:

  • nausea
  • somnolence (sleepiness)
  • dizziness - some patients also experienced "hot flashes" together with dizziness
  • reduced appetite
  • constipation

• Venlafaxine (Effexor) - Venlafaxine has fewer side effects than TCAs. There is some indication that it may be effective for cancer-related neuropathies. There is now an extended release form of venlafaxine which appears to be effective for diabetic peripheral neuropathy. Adverse reactions may include:

  • nausea