Article

Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial.

Department of Neurology, University of Wisconsin, Madison 53792, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 30.39). 01/1999; 280(21):1831-6.
Source: PubMed

ABSTRACT Pain is the most disturbing symptom of diabetic peripheral neuropathy. As many as 45% of patients with diabetes mellitus develop peripheral neuropathies.
To evaluate the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy.
Randomized, double-blind, placebo-controlled, 8-week trial conducted between July 1996 and March 1997.
Outpatient clinics at 20 sites.
The 165 patients enrolled had a 1- to 5-year history of pain attributed to diabetic neuropathy and a minimum 40-mm pain score on the Short-Form McGill Pain Questionnaire visual analogue scale.
Gabapentin (titrated from 900 to 3600 mg/d or maximum tolerated dosage) or placebo.
The primary efficacy measure was daily pain severity as measured on an 11-point Likert scale (0, no pain; 10, worst possible pain). Secondary measures included sleep interference scores, the Short-Form McGill Pain Questionnaire scores, Patient Global Impression of Change and Clinical Global Impression of Change, the Short Form-36 Quality of Life Questionnaire scores, and the Profile of Mood States results.
Eighty-four patients received gabapentin and 70 (83%) completed the study; 81 received placebo and 65 (80%) completed the study. By intent-to-treat analysis, gabapentin-treated patients' mean daily pain score at the study end point (baseline, 6.4; end point, 3.9; n = 82) was significantly lower (P<.001) compared with the placebo-treated patients' end-point score (baseline, 6.5; end point, 5.1; n = 80). All secondary outcome measures of pain were significantly better in the gabapentin group than in the placebo group. Additional statistically significant differences favoring gabapentin treatment were observed in measures of quality of life (Short Form-36 Quality of Life Questionnaire and Profile of Mood States). Adverse events experienced significantly more frequently in the gabapentin group were dizziness (20 [24%] in the gabapentin group vs 4 [4.9%] in the control group; P<.001) and somnolence (19 [23%] in the gabapentin group vs 5 [6%] in the control group; P = .003). Confusion was also more frequent in the gabapentin group (7 [8%] vs 1 [1.2%]; P = .06).
Gabapentin monotherapy appears to be efficacious for the treatment of pain and sleep interference associated with diabetic peripheral neuropathy and exhibits positive effects on mood and quality of life.

1 Bookmark
 · 
216 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Painful diabetic neuropathy (PDN) is a debilitating consequence of diabetes that may be present in as many as one in five patients with diabetes. The objective assessment of PDN is difficult, making it challenging to diagnose and assess in both clinical practice and clinical trials. No single treatment exists to prevent or reverse neuropathic changes or to provide total pain relief. Treatment of PDN is based on three major approaches: intensive glycaemic control and risk factor management, treatments based on pathogenetic mechanisms, and symptomatic pain management. Clinical guidelines recommend pain relief in PDN through the use of antidepressants such as amitriptyline and duloxetine, the γ-aminobutyric acid analogues gabapentin and pregabalin, opioids and topical agents such as capsaicin. Of these medications, duloxetine and pregabalin were approved by the US Food and Drug Administration (FDA) in 2004 and tapentadol extended release was approved in 2012 for the treatment of PDN. Proposed pathogenetic treatments include α-lipoic acid (stems reactive oxygen species formation), benfotiamine (prevents vascular damage in diabetes) and aldose-reductase inhibitors (reduces flux through the polyol pathway). There is a growing need for studies to evaluate the most potent drugs or combinations for the management of PDN to maximize pain relief and improve quality of life. A number of agents are potential candidates for future use in PDN therapy, including Nav 1.7 antagonists, N-type calcium channel blockers, NGF antibodies and angiotensin II type 2 receptor antagonists.
    Therapeutic advances in chronic disease. 01/2015; 6(1):15-28.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Diabetic neuropathy represents one of the most prevalent complications of diabetes mellitus. The aim of this study was to investigate the effect of diabetes-induced disturbances in neurons on the Ca(2+)-triggered membrane fusion process in cell-free system in relation to plasmalemma cholesterol level. The gabapentin therapy on the exocytosis process was also studied. The diabetes in rats was induced by streptozotocin (60 mg/kg of body weight, i.p.). After 4 weeks of diabetes induction the one group of diabetic rats was treated with gabapentin (50 mg/kg, i.p.) during 1 month. Fusion experiments were performed in the cell-free model system using fluorescent dye octadecylrhodamine B. The [2-(14)C]serotonin preloaded synaptosomes were used for assay of stimulated neurotransmitter release. The synaptosomal plasma membrane cholesterol level in diabetic rats was on 12 % higher than in control and was decreased on 5 % after gabapentin therapy. The rate of synaptic vesicles fusion with plasma membranes in the presence of Ca(2+) and synaptosomal cytosolic proteins was decreased to 14.5 % in diabetic rats as compared to control (23 %) and after gabapentin administration to diabetic rats was raised to 18 %. At diabetes the stimulated synaptosomal serotonin release was increased in 1.7-2 folds and was partially normalized by gabapentin therapy. Together, these findings suggest that elevated cholesterol content in neuronal plasma membranes at diabetes impairs the membrane fusion process in neurons that can induce the development of neuropathy. Diabetes-evoked impairments of the exocytotic process can be attenuated by gabapentin therapy.
    Neurochemical Research 01/2015; · 2.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: One of the most frequent problems in medical care is the management of patient presenting with chronic pain. Neuropathic pain is related to the injury or disorders affecting peripheral and central nervous systems and is resistant to over-the-counter analgesics and conventional treatment methods. The estimated prevalence for patients presenting classical symptoms of neuropathic pain is eventually reported to be 6%–8%. Several mechanisms have been considered and proposed for this disorder. The involvement of small and large sensory fibers as well as motor fibers is a reason for the presence of neuropathic pain. In addition to the lifestyle modification, a number of different therapeutic approaches and treatment protocols have been applied to control the neuropathic pain. However, management is still unsatisfactory. Comorbidities such as depression, anxiety, and sleep disorders are associated with this disorder and should be previously considered and eliminated. Analgesics, tricyclic antidepressants, anticonvulsant, serotonin– norepinephrine reuptake inhibitors, and local anesthetic agent as well as opioid analgesics and herbal medicaments such as capsaicin are known treatment lines for the management of neuropathic pain. Regarding the unsuccessfulness of single therapy, poly-pharmacy or combination therapy of two or more agents with synergistic mechanisms and different modes of action seems necessary.
    National Journal of Physiology, Pharmacy and Pharmacology. 01/2015; 5(3).

Full-text (2 Sources)

Download
2,159 Downloads
Available from
May 16, 2014