Diabetes mellitus is the most common cause of peripheral neuropathy, with 45 percent of patients affected at some time during the course of their disease. Pain is typically localized to the feet and ankles but may affect other areas. Peripheral neuropathy is difficult to treat successfully; tricyclic antidepressants are effective at reducing pain, but intolerable side effects often limit their use. Inadequate treatment can affect mood and sleep patterns, as well as fail to provide pain relief. Gabapentin is a fairly new anticonvulsant agent that has successfully reduced pain syndromes in some studies. This effect may be due to its relationship to γ-aminobutyric acid (GABA), a neuro-transmitter that modulates pain. Backonja and associates evaluated the effectiveness of gabapentin in treating neuropathic pain in patients with diabetes mellitus.
Patients with diabetes mellitus and peripheral pain diagnosed as diabetic neuropathy were eligible for this randomized controlled trial if they rated their pain at a score of at least 40 on a 100-point scale. Other study criteria included a hemoglobin A1c level of no more than 0.11. Exclusion criteria included other types of severe pain that could interfere with the study assessment and a creatinine clearance of less than 60 mL per minute (1.00 mL per second), because impaired renal function necessitates adjusting the dosage of gabapentin. Acetaminophen and aspirin were the only medications allowed that might affect the symptoms of painful neuropathy.
During the screening phase of the study, a medical history and physical examination were obtained, as were blood studies to evaluate serum creatinine and hemoglobin A1c levels. Patients completed daily pain and sleep diaries during this phase of the study. Patients who met the inclusion criteria were then randomized to receive gabapentin or placebo for eight weeks. The starting dosage of gabapentin was 900 mg daily. This was gradually increased to a maximum of 3,600 mg daily over the course of the first four weeks, regardless of any efficacy achieved at a lower dosage. For the remaining four weeks, patients remained at the maximum dosage if they could tolerate it. If not, they could decrease the total daily dosage of gabapentin to a minimum of 900 mg daily. All patients kept daily pain and sleep diaries, and recorded information on overall quality of life. The primary end point of the study was a rating of pain severity. Secondary end points included disturbances in sleep patterns and changes in overall quality of life.
Of the 165 patients enrolled in the study, 84 were in the treatment group and 81 in the placebo group. Demographic and baseline characteristics, including pain scores and the extent of neuropathic pain, were similar between groups. In addition, the number of patients who completed the study and the number who withdrew because of adverse effects were also comparable. Mean pain scores and mean sleep interference scores were significantly improved in the treatment group compared with the placebo group. Quality of life was also improved in the treatment group. Hemoglobin levels did not appreciably change in either group, suggesting that gabapentin had no effect on glycemic control. Adverse effects of the drug were considered to be mild to moderate and included dizziness, somnolence, nausea and headache. Side effects associated with the placebo included dyspepsia, constipation and flatulence.
The authors conclude that gabapentin provides safe, effective pain relief in patients with diabetic neuropathy. The effects of gabapentin are similar to those found with tricyclic antidepressants but with a more rapid onset of action and fewer adverse effects. The adverse effects experienced with gabapentin were generally mild and are potentially avoidable with dosage adjustment.