Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial

Abstract

A randomized, double-blind, placebo-controlled, parallel-group, multicenter, 8-week trial (with subsequent open-label phase) evaluated the effectiveness of pregabalin in alleviating pain associated with diabetic peripheral neuropathy (DPN). For enrollment, patients must have had at baseline: 1- to 5-year history of DPN pain; pain score > or =40 mm (Short-Form McGill Pain Questionnaire [SF-MPQ] visual analogue scale); average daily pain score of > or =4 (11-point numerical pain rating scale [0 = no pain, 10 = worst possible pain]). One hundred forty-six (146) patients were randomized to receive placebo (n = 70) or pregabalin 300 mg/day (n = 76). Primary efficacy measure was endpoint mean pain score from daily patient diaries (11-point numerical pain rating scale). Secondary measures included SF-MPQ scores; sleep interference scores; Patient and Clinical Global Impression of Change (PGIC and CGIC); Short Form-36 (SF-36) Health Survey scores; and Profile of Mood States (POMS) scores. Safety assessment included incidence and intensity of adverse events, physical and neurological examinations, and laboratory evaluations. Pregabalin produced significant improvements versus placebo for mean pain scores (P < 0.0001); mean sleep interference scores SF-36 Bodily Pain subscale (P < 0.0001); total SF-MPQ score (P < 0.01); SF-36 Bodily Pain subscale (P < 0.03); PGIC (P = 0.001); and Total Mood Disturbance and Tension-Anxiety components of POMS (P < 0.03). Pain relief and improved sleep began during week 1 and remained significant throughout the study (P < 0.01). Pregabalin was well tolerated despite a greater incidence of dizziness and somnolence than placebo. Most adverse events were mild to moderate and did not result in withdrawal. Pregabalin was safe and effective in decreasing pain associated with DPN, and also improved mood, sleep disturbance, and quality of life.

Efficacy and Safety of Mirogabalin (DS-5565) for the Treatment of Diabetic Peripheral Neuropathic Pain: A Randomized, Double-Blind, Placebo- and Active Comparator–Controlled, Adaptive Proof-of-Concept Phase 2 Study

“…Beginning at week 1, the highest three mirogabalin dosing groups (15,20, and 30 mg/day) had significantly greater mean reductions from baseline to week 5 in ADPS compared with placebo, and one dosing group (30 mg/day) met the criteria for minimally clinically meaningful effect (i.e., a decrease $1.0 point versus placebo). These data are compelling given the study population had DPNP for a mean of 5.8 years, which is longer than those who participated in pregabalin trials, where subjects were excluded if the duration of DPNP was .5 years (20,(23)(24)(25). Analysis of responders, defined as subjects who attained $30 or $50% reduction from baseline in ADPS, were generally supportive of a mirogabalin treatment effect compared with placebo, as improvements relative to placebo were statistically significant at 15-, 20-, and 30-mg/day dose levels using one or both responder definitions.…”

“…1. No titration was used in mirogabalin 5-, 10-, 15-, and 20-mg/day dosing arms to assess quicker pain relief (20).…”

Use of Antiepileptic Drugs for Nonepileptic Conditions: Psychiatric Disorders and Chronic Pain

“…In a separate randomized controlled PHN trial, Sabatowski et al 84 found that, at a dose of 300 mg/day compared with placebo, patients receiving pregabalin not only had significant pain reduction but also enjoyed improvement in sleep and mood. In another eight-week randomized placebo-controlled trial, Rosenstock et al 85 evaluated the potential efficacy of pregabalin in reducing pain associated with DPN. Use of pregabalin at a dose of 300 mg/day resulted in significant improvements in mean pain scores, the patient, and clinical global impression of change scores on the Short Form-36 Health Survey, and mean sleep interference scores.…”

Latest Approaches for the Treatment of Spasticity and Autonomic Dysreflexia in Chronic Spinal Cord Injury

“…Similar to gabapentin, pregabalin was developed as a treatment for epileptic seizures, but it has evolved to include other indications, such as neuropathic pain [50,51]. Their mechanisms of action require the binding to the high affinity α2-delta subunit protein of the voltagegated Ca 2+ channels [52], thereby reducing release of excitatory neurotransmitters in the central nervous system [53].…”