Mathieson S1, Maher C1, McLachlan A2, Latimer J1, Koes B3, Hancock M4, Harris I5, Day R6, Billot L7, Pik J8, Jan S9, Lin C1
1The University of Sydney, Institute for Musculoskeletal Health, Sydney, Australia, 2The University of Sydney, Sydney School of Pharmacy, Sydney, Australia, 3Erasmus University Medical Center, Department of General Practice, Rotterdam, Netherlands, 4Macquarie University, Faculty of Medicine and Health Science, Sydney, Australia, 5University of New South Wales, Ingham Institute for Applied Medical Research, South Western Sydney Clinical School, Sydney, Australia, 6University of New South Wales, St. Vincent’s Clinical School, Sydney, Australia, 7The George Institute for Global Health, Statistics, Sydney, Australia, 8NeuroSpine Clinic, Canberra, Australia, 9The George Institute for Global Health, Health Economics and Process Evaluation Program, Sydney, Australia
Background: Sciatica is characterised by radiating leg pain and evidence regarding medical treatments is limited. There is increasing use of pharmacological treatments rather than physical activity in spinal pain conditions such as sciatica, especially strong medicines like the neuropathic pain medicine pregabalin. Pregabalin is effective in treating some neuropathic pain conditions (e.g. post-herpetic neuralgia), but robust evidence is lacking for its use in reducing the neuropathic pain component associated with sciatica.
Purpose: To determine the efficacy and safety of pregabalin in reducing leg pain intensity in patients with sciatica by conducting a randomised, double-blind, placebo-controlled trial (Australian and New Zealand Clinical Trials Registry number ACTRN12613000530729).
Methods: Patients who visited a trial clinician as an outpatient in New South Wales Australia, for moderate-to-severe sciatica were considered for trial recruitment. Sciatica was defined in this trial as radiating pain into one leg below the knee, accompanied by nerve-root or spinal nerve involvement as indicated by the presence of at least one of the following clinical features: dermatomal leg pain, myotomal weakness, sensory deficits, or diminished reflex, as determined by the trial clinician. All participants received advice (e.g. to remain active) and reassurance regarding the cause of symptoms and that symptoms usually diminish over time. Randomised participants also received either pregabalin at 150mg/day, adjusted to ≤600mg/day or matching placebo for up to 8 weeks depending on tolerability, monitored weekly. The primary outcome was the leg-pain intensity, scored from zero (no pain) to 10 (worst possible pain). Secondary outcomes included the extent of disability, back-pain intensity and quality-of-life measures. Outcomes were measured at pre-specified time points over one year, with week eight as the primary time-point.
Results: A total of 209 patients underwent randomisation; 108 received pregabalin and 101 received placebo. At week 8, the mean unadjusted leg-pain intensity score was 3.7 in the pregabalin group and 3.1 in the placebo group (adjusted mean difference [MD], 0.5; 95% confidence interval [CI], −0.2 to 1.2; P = 0.19). At week 52, the mean unadjusted leg-pain intensity score was 3.4 in the pregabalin group and 3.0 in the placebo group (adjusted MD, 0.3; 95% CI, −0.5 to 1.0; P = 0.46). No significant between-group differences were observed in any secondary outcome. More adverse events were reported in the pregabalin group (nevents=227) versus the placebo group (nevents=124), with dizziness the most common adverse event reported in both groups.
Conclusion(s): Pregabalin did not significantly reduce the intensity of leg pain associated with sciatica nor significantly improve any other outcomes compared with placebo at week 8 or at one year. However, the incidence of adverse events was significantly higher in the pregabalin group than in the placebo group.
Implications: Pregabalin should not be routinely prescribed to patients with sciatica.
Keywords: Sciatica, Neuropathic pain, Pregabalin
Funding acknowledgements: The trial received grant support from the National Health and Medical Research Council of Australia (NHMRC) (ID APP1042073).
Purpose: To determine the efficacy and safety of pregabalin in reducing leg pain intensity in patients with sciatica by conducting a randomised, double-blind, placebo-controlled trial (Australian and New Zealand Clinical Trials Registry number ACTRN12613000530729).
Methods: Patients who visited a trial clinician as an outpatient in New South Wales Australia, for moderate-to-severe sciatica were considered for trial recruitment. Sciatica was defined in this trial as radiating pain into one leg below the knee, accompanied by nerve-root or spinal nerve involvement as indicated by the presence of at least one of the following clinical features: dermatomal leg pain, myotomal weakness, sensory deficits, or diminished reflex, as determined by the trial clinician. All participants received advice (e.g. to remain active) and reassurance regarding the cause of symptoms and that symptoms usually diminish over time. Randomised participants also received either pregabalin at 150mg/day, adjusted to ≤600mg/day or matching placebo for up to 8 weeks depending on tolerability, monitored weekly. The primary outcome was the leg-pain intensity, scored from zero (no pain) to 10 (worst possible pain). Secondary outcomes included the extent of disability, back-pain intensity and quality-of-life measures. Outcomes were measured at pre-specified time points over one year, with week eight as the primary time-point.
Results: A total of 209 patients underwent randomisation; 108 received pregabalin and 101 received placebo. At week 8, the mean unadjusted leg-pain intensity score was 3.7 in the pregabalin group and 3.1 in the placebo group (adjusted mean difference [MD], 0.5; 95% confidence interval [CI], −0.2 to 1.2; P = 0.19). At week 52, the mean unadjusted leg-pain intensity score was 3.4 in the pregabalin group and 3.0 in the placebo group (adjusted MD, 0.3; 95% CI, −0.5 to 1.0; P = 0.46). No significant between-group differences were observed in any secondary outcome. More adverse events were reported in the pregabalin group (nevents=227) versus the placebo group (nevents=124), with dizziness the most common adverse event reported in both groups.
Conclusion(s): Pregabalin did not significantly reduce the intensity of leg pain associated with sciatica nor significantly improve any other outcomes compared with placebo at week 8 or at one year. However, the incidence of adverse events was significantly higher in the pregabalin group than in the placebo group.
Implications: Pregabalin should not be routinely prescribed to patients with sciatica.
Keywords: Sciatica, Neuropathic pain, Pregabalin
Funding acknowledgements: The trial received grant support from the National Health and Medical Research Council of Australia (NHMRC) (ID APP1042073).
Topic: Musculoskeletal; Primary health care; Pain & pain management
Ethics approval required: Yes
Institution: The University of Sydney
Ethics committee: University of Sydney Human Research Ethics Committee
Ethics number: Protocol number 15333
All authors, affiliations and abstracts have been published as submitted.
