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Abstract & Commentary
Source: Davis JL, Smith RL. Painful peripheral diabetic neuropathy treated with venlafaxine HCl extended release capsules. Diabetes Care 1999;22(11):1909-1910.
Despite many advances in the treatment of diabetes mellitus, diabetic neuropathy (DN) remains a common clinical dilemma. Even when maintaining tight glycemic control, patients may develop DN, which can be difficult to treat. Pharmacotherapy for DN involves many different types of agents, including aldose reductase inhibitors, mexiletine, capsaicin, gabapentin, carbamazepine, and tricyclic antidepressants (TCAs). However, in many cases these medications either fail to provide adequate relief or are difficult to tolerate. The current series of cases suggest that extended release venlafaxine (Effexor XR) may be useful in the treatment of DN.
The first case involved a 41-year-old man who was diagnosed with diabetes after presenting with mild nocturia. He was found to have blood glucose levels of approximately 200 mg/dL. Approximately seven months after treatment with dietary modification and glipizide 10 mg/d, he developed severe burning paresthesia around the mid-tibial region, necessitating that he not wear shoes. He experienced no relief from acetaminophen, codeine, or amitriptyline. The patient was started on venlafaxine extended release capsules at 75 mg/d and experienced 95% relief within five days. The pain recurred five days after discontinuing venlafaxine and remitted once again approximately three days after restarting the drug.
Due to the remarkable response shown in this patient, 10 additional patients (age 35-71) were initiated on venlafaxine 37.5-75 mg/d. The duration of diabetes for this group varied from 2-25 years. All patients had been treated with oral hypoglycemics alone or in combination with insulin. All patients, who had failed previous trials of medications such as TCAs, experienced approximately 75-100% reduction in pain within 3-14 days after the initiation of venlafaxine. Extended release venlafaxine was well tolerated by all subjects.
Comment by Michael F. Barber, pharmD
The current article suggests that venlafaxine extended release capsules may be effective and well tolerated in the treatment of DN. Since this was a nonrandomized study, a placebo response cannot be ruled out. However, the reported results were striking, especially since the participants had failed previous trials of other agents. Venlafaxine is an antidepressant that inhibits the reuptake of serotonin, norepinephrine, and, to some extent, dopamine, in a dose-dependent manner. Tricyclic antidepressants also inhibit the reuptake of serotonin and norepinephrine, but tend to have more side effects because of additional effects on alpha adrenergic, muscarinic, and histaminic receptors. Davis and Smith hypothesized that the patient’s mixed neuotransmitter profile is associated with greater efficacy in treating DN compared to prior studies with fluoxetine, which is more selective for serotonin reuptake. However, in the relatively modest doses used in this series, the primary effect of venlafaxine would be inhibition of the reuptake of serotonin. As such, there may be a more complex reason for the differences in response between venlafaxine and fluoxetine if such a difference is indeed demonstrated in head-to-head randomized studies. Venlafaxine is usually well tolerated, particularly when the extended release capsules are used. One of the more concerning side effects of venlafaxine is an increase in blood pressure. This effect is dose-dependent, with clinically important blood pressure increases usually only taking places in doses of 225 mg/d or higher.
In conclusion, while venlafaxine may be effective in the treatment of DN, controlled trials are required before venlafaxine can be considered as a front-line agent. However, venlafaxine should be considered when other agents are unsuccessful in the treatment of DN.