[Note: Pregabalin, brand name Lyrica, is an anti-seizure drug prescribed for neuropathic pain (from damaged nerves) in diabetes and shingles. It recently received FDA approval as a treatment for fibromyalgia.]
Background: Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions.
Objectives: To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain.
Search strategy: We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified from the reference lists of retrieved papers and on-line clinical trial databases.
Selection criteria: Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome.
Data collection and analysis: Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals.
Main results: There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic nociceptive pain, like arthritis.
Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants).
Pregabalin at 150 mg daily was generally ineffective.
Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose.
The best (lowest) numbers-needed-to-treat-to-benefit for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were:
• 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia,
• 5.0 (4.0 to 6.6) for painful diabetic neuropathy,
• 5.6 (3.5 to 14) for central neuropathic pain, and
• 11 (7.1 to 21) for fibromyalgia.
With 600 mg pregabalin daily:
• Somnolence typically occurred in 15% to 25%
• And dizziness occurred in 27% to 46%.
• Treatment was discontinued due to adverse events in 18% to 28%.
The proportion of participants reporting at least one adverse event was not affected by dose, nor was the number with a serious adverse event, which was not more than with placebo.
Higher rates of substantial benefit were found in postherpetic neuralgia and painful diabetic neuropathy than in central neuropathic pain and fibromyalgia.
• For moderate and substantial benefit on any outcome, numbers-needed-to-treat-to-benefit for the former [postherpetic neuralgia] were generally six and below for 300 mg and 600 mg daily;
• For fibromyalgia numbers-needed-to-treat-to-benefit were much higher, and generally seven and above.
Authors' conclusions: Pregabalin has proven efficacy in neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events. Individualisation of treatment is needed to maximise pain relief and minimise adverse events. There is no evidence to support the use of pregabalin in acute pain scenarios.
Plain language summary
Pregabalin for acute and chronic pain in adults
Pregabalin relieves pain caused by damage to nerves, either from injury or disease. Antiepileptics (such as pregabalin) are medicines used for treating epilepsy, but are also effective for treating pain. The type of pain that responds well to pregabalin treatment is neuropathic pain (pain caused by damage to nerves). This includes postherpetic neuralgia (persistent pain in an area previously affected by shingles) and painful complications of diabetes, as well as fibromyalgia.
Only a minority of patients with these types of pain will have a substantial benefit, and somewhat more will have moderate benefit.
With pregabalin daily doses of 300 mg to 600 mg, the patient global impression of change rating of much or very much improved was about 35% in postherpetic neuralgia, 50% in painful diabetic neuropathy, and 40% in fibromyalgia.
There is no evidence that pregabalin is effective in acute conditions where pain is already established, and in chronic conditions in which nerve damage is not the prime source of the pain, such as arthritis.
Source: Cochrane Database of Systematic Reviews, Jul 8, 2009;(3):CD007076. PMID: 19588419, by Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pain Research and Nuffield Department of Anaesthetics, University of Oxford, John Radcliffe Hospital, Oxford, Oxfordshire, UK. [E-mail: email@example.com]