Diabetic Neuropathy - Treatment

Gabapentin - updated: 25 January 2009

Evidence for the use of gabapentin in the treatment of diabetic peripheral neuropathy

Clin Ther. 2001 Apr;23(4):520-31

Hemstreet B, Lapointe M.

BACKGROUND: One of the most common peripheral nerve complications of diabetes is painful diabetic peripheral neuropathy (DPN). Although tricyclic antidepressants (TCAs) have traditionally been used to relieve the pain of this condition, gabapentin's reported efficacy in various neuropathic pain states and its favorable side-effect profile compared with other available agents have led to interest in the use of this agent for the treatment of DPN. OBJECTIVES: This paper reviews the current clinical literature on the effectiveness and tolerability of gabapentin in the treatment of DPN. It also considers whether the evidence favors gabapentin's use as an alternative or first-line agent. METHODS: A search of the English- and French-language literature for the years 1990 through 2000 was performed using MEDLINE, Current Contents/Clinical Medicine, and International Pharmaceutical Abstracts, plus the reference lists of the articles identified through this search. The search terms used were gabapentin, anticonvulsant, diabetic peripheral neuropathy, and neuropathy. Included studies were limited to trials in human subjects. RESULTS: The literature search identified several case reports and case series, as well as 3 small placebo-controlled studies (2 complete, 1 brief report) and 1 comparative trial against the TCA amitriptyline. The designs and dosing regimens differed between studies. CONCLUSIONS: Many clinicians consider gabapentin an alternative treatment option in patients with DPN who are unable to tolerate traditional agents or in whom traditional agents are contraindicated. To date, gabapentin has been well tolerated, superior to placebo, and equivalent to amitriptyline in small clinical trials of short duration. Although overall efficacy and safety profiles appear to be favorable, larger long-term studies are needed to determine the place of gabapentin in relation to other treatment options. There is currently insufficient evidence from controlled trials to support the use of gabapentin as first-line therapy for DPN.

Publication Types:

• Review

Prolonged-release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients

Eur J Pain. 2008 Aug;12(6):804-13.

Hanna M, O'Brien C, Wilson MC.

BACKGROUND: Neuropathic pain remains one of the most challenging pain syndromes; under-diagnosed, poorly managed and associated with significant co-morbidity. With standard therapeutic treatments, responders rarely exceed 50% pain relief and the majority suffer from residual pain. Titration to optimum dose is often limited by dose-related adverse events. AIMS: This randomized, double-blind, placebo-controlled study assessed the potential benefit of adding oxycodone (OxyContin tablets) to gabapentin. The primary endpoint was to evaluate the analgesic efficacy of co-administration of gabapentin and prolonged-release oxycodone, whilst also evaluating the use of escape medication, sleep quality and global assessment of pain. METHODS: Three hundred and thirty eight patients with moderate to severe painful diabetic neuropathy despite receiving their maximum tolerated dose of gabapentin, had oral prolonged-release oxycodone or placebo tablets added to their therapy for up to 12 weeks. RESULTS: Oxycodone-gabapentin reduced pain score by 33% from baseline to end of treatment. The overall treatment effect was greater with oxycodone-gabapentin than with placebo-gabapentin (P = 0.007). Oxycodone-gabapentin also significantly improved pain relief vs gabapentin alone (P = 0.003). Oxycodone-gabapentin co-administration was associated with less escape medication use (P = 0.03) and fewer nights of disturbed sleep (P < 0.05). Discontinuations due to lack of therapeutic effect were much lower (14% vs 54%) with oxycodone-gabapentin. The commonly seen opiate-induced adverse events were not exacerbated by the combination of oxycodone and gabapentin. CONCLUSIONS: This study provides the first evidence that co-administration of prolonged-release oxycodone and existing gabapentin therapy has a clinically meaningful effect in painful diabetic neuropathy

Publication Types:

• Placebo controlled

Gabapentin dosing for neuropathic pain: evidence from randomized, placebo-controlled clinical trials

Clin Ther. 2003 Jan;25(1):81-104

Backonja M, Glanzman RL.

BACKGROUND: Pain is one of the most common reasons for seeking medical attention, and neuropathic pain is among the most common types of pain. Despite its prevalence, neuropathic pain is often underrecognized and inadequately treated. Many cases are refractory to the medications traditionally used for pain, such as nonsteroidal anti-inflammatory drugs. Tricyclic antidepressants are considered first-line agents for neuropathic pain, but their use is limited by unwanted side effects and a risk of cardiovascular mortality. OBJECTIVES: The goals of this article were to review data on the efficacy and tolerability of gabapentin in the treatment of neuropathic pain in adults and to determine the optimal dosing schedule. METHODS: Randomized controlled studies of gabapentin for neuropathic pain were identified through a search of PubMed and MEDLINE from 1966 to the present using the search terms gabapentin, randomized, placebo, and pain. Abstracts of identified articles were screened for study size (>100 patients per treatment arm) and use of appropriate efficacy measures. A separate review based on information provided by the manufacturer of gabapentinaand clinical trial Web sites was conducted to ascertain whether there had been any other relevant industry- or government-sponsored trials. The manufacturer provided additional unpublshed study data. RESULTS: Data from 5 randomized, placebo-controlled trials were included in the review, 1 of which has not yet been published. Gabapentin was effective in the treatment of painful diabetic neuropathy, postherpetic neuralgia, and other neuropathic pain syndromes. It relieved symptoms of allodynia, burning pain, shooting pain, and hyperesthesia. Adverse effects were typically mild to moderate and usually subsided within approximately 10 days from the initiation of treatment. Based on available data, it appears that treatment should be started at a dose of 900 mg/d (300 mg/d on day 1, 600 mg/d on day 2, and 900 mg/d on day 3). Additional titration to 1800 mg/d is recommended for greater efficacy. Doses up to 3600 mg/d may be needed in some patients. The effective dose should be individualized according to patient response and tolerability. CONCLUSION: At doses of 1800 to 3600 mg/d, gabapentin was effective and well tolerated in the treatment of adults with neuropathic pain.

Publication Types:

• Review

Gabapentin monotherapy for the symptomatic treatment of painful neuropathy: a multicenter, double-blind, placebo-controlled trial in patients with diabetes mellitus

Epilepsia. 1999;40 Suppl 6:S57-9

Backonja MM.

Pain is the most disturbing symptom of diabetic neuropathy. Traditionally this type of pain was treated with tricyclic antidepressants which frequently have many side effects. In the study reported here, gabapentin was administered in escalating doses up to 3600 mg per day to eligible patients with moderate to severe diabetic neuropathy pain in a double blind placebo controlled fashion. Gabapentin provided superior and significant pain relief over placebo. In addition, patients taking gabapentin had improvement of sleep scores and a number of items on mood and quality of life questionnaires. Gabapentin was tolerated well with mild and tolerable side effects.

Publication Types:

• a multicenter, double-blind, placebo-controlled trial

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

JAMA. 1998 Dec 2;280(21):1831-6

Backonja M, Beydoun A, Edwards KR, Schwartz SL, Fonseca V, Hes M, LaMoreaux L, Garofalo E.

CONTEXT: Pain is the most disturbing symptom of diabetic peripheral neuropathy. As many as 45% of patients with diabetes mellitus develop peripheral neuropathies. OBJECTIVE: To evaluate the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy. DESIGN: Randomized, double-blind, placebo-controlled, 8-week trial conducted between July 1996 and March 1997. SETTING: Outpatient clinics at 20 sites. PATIENTS: 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. INTERVENTION: Gabapentin (titrated from 900 to 3600 mg/d or maximum tolerated dosage) or placebo. MAIN OUTCOME MEASURES: 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. 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). CONCLUSION: 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.

Publication Types:

• randomized controlled trial

Publication Types:

• Review