ISSN No. 1606-7754                   Vol.10 No.1 April 2002

First line symptomatic therapy for painful diabetic neuropathy (PDN): A tricyclic antidepressant or gabapentin?
Georg Petroianu, Andrea Schmitt
Dept. of Physiology and Pharmacology, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates;  Central Institute of Mental Health, PO Box 122120, 68072 Manheim, Germany

Abstract

Diabetes is a high prevalence disease leading among others to painful diabetic neuropathy (PDN). Tricyclic antidepressants (TCA) were considered as first line therapy for symptomatic pain therapy. While their efficacy is reasonably well established, their adverse drug reaction (ADR) profile limits their usefulness. Third generation antidepressants like venlafaxine could overcome these limitations but data concerning their efficacy are limited. Among clinicians a new therapeutic trend is occurring: gabapentin, a drug initially marketed as an antiepileptic, is becoming increasingly popular as the first line therapy for PDN. Gabapentin is a ligand for the alpha2/delta modulatory subunit of calcium channels, thus decreasing intracellular calcium availability. Initial data on the effectiveness of gabapentin in PDN indicates an efficacy comparable with secondary amine TCAs. The reason for gabapentinís popularity is the benign ADR profile and the lack of relevant drug-drug or drug-food interactions.

Key words: Painful diabetic neuropathy, tricyclic antidepressants (TCA),symptomatic pain therapy, gabapentin

Introduction

Diabetes affects over 15 million people in the United States, or 5.9 percent of the population. While an estimated 10 million people have been diagnosed, 5 million are not aware that they have the disease. The reported prevalence varies but generally seems to be on the rise. The number of Americans with diagnosed diabetes is projected to increase by 165%, from 10 million in 2000 (prevalence of 4.0%) to 29 million in 2050 (prevalence of 7.2%).1 For Ontario, Canada, the all-age prevalence increased from 3.2% in 1993 to 4.5% in 1998 (6.1% in adults); however, the incidence remained stable.2 Data from a city in India shows a prevalence of known diabetes of 2.9% for all ages and both sexes combined (prevalence 10.5% in those aged 40 years).3 For Phillipino-Americans aged 20-74 years, overall prevalence was estimated to be 16.1%.4 Using a very conservative approach and assuming a worldwide all-ages prevalence of 3%, the total number of diabetic patients can be estimated as being over 150 million.

The prevalence of diabetic neuropathy varies from 10% within 1 year of diagnosis to 50% in patients having the disease for more than 25 years.5 As such the numbers for patients having diabetic neuropathy range from 15-75 million. A minority, probably one order of magnitude lower, will develop Painful Diabetic Neuropathy (PDN). Treatment of diabetic neuropathy is multi-layered, including aetiology driven causal treatment, elimination of risk factors, and symptomatic therapy (i.e., chronic pain therapy).

The focus of this review is the two top contenders for the title "drug of choice" for symptomatic pharmacological therapy in PDN: antidepressants and gabapentin. After reviewing pharmacokinetic, pharmacodynamic, and clinical efficacy aspects of the two drug classes, an attempt is made to address the question which drug, a tricyclic antidepressant or gabapentin, is the drug of choice for PND?

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