Diabetic peripheral neuropathy is very common sequelae of diabetes mellitus. Patients often complain of burning, tingling, numbness and even sharp stabbing pain. These symptoms can cause sleep disturbances as well as problems with daily activities. Many primary care physicians and podiatrists overlook these symptoms which, in most cases, have been going on for years. Many people are unaware of the medications that can help relieve the discomfort. At our facility, we are very aggressive in treating diabetic neuropathy and feel that it is very important in our treatment regimen. With this in mind, let’s take a closer look at the most common medications, contraindications, adverse effects and our experience in using these medications. Carbamazepine (tegretol) is an anti-epileptic drug that inhibits Ad and C pain fibers without interfering with normal nerve conduction. It is most frequently used in trigeminal neuralgia and diabetic neuropathy. According to Ahmad, et. al., carbamazepine is more effective against the paroxysmal shooting and lancinating pain and less effective against the constant burning pain experienced by patients with painful neuropathy.1 The most common side effects of carbamazepine include dizziness, somnolence and gait disturbances. In elderly patients, carbamazepine has been associated with an increased frequency of hyponatremia and cardiac conduction defects, which may lead to inappropriate antidiuretic hormone (ADH) secretion. Serum levels between 6 to 10 mg/L were found to be therapeutic and this corresponded to a dosage range of 400 to 1,000 mg/day.1 One study showed that 600 mg/day of carbamazepine was more effective than placebo.2 Leukopenia and thrombocytopenia occur in less than 10 percent of patients, which may be a concern in the elderly population. Therefore, you should obtain a complete blood count and liver function tests before initiating therapy and repeat this testing every six months. Should You Consider Tricyclic Antidepressants? Tricyclic antidepressants (TCAs) have been used for decades to treat neuropathic pain. These agents inhibit the reuptake of serotonin and norepinephrine into presynaptic terminals. There have been many studies that have proven the TCAs to be not only beneficial in diabetic neuropathy but in treating other neuropathic diseases as well. The problem lies in the fact that these drugs also inhibit many other types of receptors, which leads to a high incidence of side effects. The elderly are prone to these effects, which include heart block, orthostatic hypotension, dry mouth, urinary retention and constipation. The most commonly used TCAs are amitriptyline, nortriptyline, imipramine and clomipramine. Using TCAs in patients with heart block, narrow angle glaucoma and prostatism is probably contraindicated.1 If sedation is a problem, then using a small dose at bedtime may be beneficial. The analgesic dosages are smaller than the antidepressant dose. If these adverse effects are problematic, then consider the secondary amine compounds (nortriptyline or desipramine) as they have fewer anticholinergic effects.3 We have found that most patients who have tried these agents in the past are reluctant to use them again. Therefore, we are using these agents less than some of the newer drugs. Key Insights On Gabapentin Gabapentin, which was originally used in treating seizures, has become a very popular drug in relieving neuropathic pain. It does not have any direct effect on GABA-ergic receptors nor does it affect GABA uptake or metabolism. Although the mechanism of action is unknown, gabapentin (Neurontin) does bind with subunits of calcium channels. In one study, gabapentin has significant pain relief scores compared to placebo. The dosages range from 300 to 3,600 mg/day but most patients achieved pain relief beyond the dosage of 1,800 mg/day. A very common mistake we see is physicians routinely underdosing their patients. When using gabapentin, you should initiate treatment with a test dose of 100 mg for elderly patients and gradually increase the dosage by 100 to 300 mg every three to five days. The median effective daily dose ranges between 900 to 1,200 mg but some patients may require a higher dosage.