Lyrica (pregabalin) is an anti-epileptic drug indicated for the treatment of neuropathic pain associated with diabetic peripheral neuropathy (DPN).
Developed by Pfizer, Lyrica was first approved across Europe in July 2004 for use in the management of peripheral neuropathic pain, as well as adjunctive therapy in the treatment of partial epileptic seizures.
Subsequently, the company gained US Food and Drug Administration (FDA) approval in December 2004 for the use of Lyrica in neuropathic pain associated with DPN and postherpetic neuralgia (PHN), making it the first FDA-approved treatment for neuropathic pain.
In September 2009, Pfizer was found guilty of misbranding drugs with the aim to defraud or mislead, receiving a $2.3bn fine. A company subsidiary was promoting four drugs, including Lyrica, for uses not approved by the FDA.
In October 2017, Lyrica CR extended-release tablets were approved by the FDA as a once-daily treatment for the management of neuropathic pain associated with DPN and PHN.
Lyrica is also approved in the US for adults suffering from pain due to fibromyalgia, spinal cord injury, and shingles. It is also approved as an adjuvant medication for the treatment of partial-onset seizures in individuals aged four years and older.
Lyrica is currently approved in more than 120 countries and regions, including Japan and Canada.
Neuropathic pain causes and symptoms
Neuropathic pain is chronic pain that arises from damage to sensory nerves. It can include pain arising from trapped or compressed nerves, drug-induced nerve damage, diabetic neuropathy, post-herpetic pain, phantom limb syndrome following limb amputation, peripheral neuropathy and fibromyalgia.
Neuropathic pain generally does not respond to treatment with opioid or non-steroidal anti-inflammatory drugs (NSAIDs).
Lyrica’s mechanism of action
Lyrica works by binding to the alpha2-delta site of voltage-sensitive calcium channels (VSCC) present in the central nervous system tissues. It blocks the calcium channels and reduces calcium-dependent release of pro-nociceptive neurotransmitters thereby generating anti-nociceptive and antiseizure effects.
Clinical studies on Lyrica
Lyrica’s efficacy was demonstrated in a number of clinical trials, including those in patients with diabetic neuropathy and fibromyalgia.
A double-blind, placebo-controlled monotherapy study in 529 patients with fibromyalgia, for example, showed that eight weeks’ treatment with Lyrica 150mg to 450mg per day produced significantly greater reductions in pain compared with placebo, as well as improved sleep quality and fatigue.
Pain, sleep disturbances and fatigue are core symptoms of fibromyalgia, which has proved an extremely difficult condition to treat.
Data from a series of phase I and II placebo-controlled clinical studies in more than 1,200 patients with generalised anxiety disorder suggested that Lyrica was effective for this disabling disorder. In comparison with venlafaxine, pregabalin provided more rapid relief of psychic and somatic symptoms.
In comparison with alprazolam (a benzodiazepine), Lyrica appeared equally effective in reducing somatic symptoms. Overall, these findings showed that Lyrica combined the benefits of antidepressants and benzodiazepines. It appeared at least as rapid as benzodiazepines against somatic symptoms while providing more rapid control of psychic symptoms than antidepressants.
The FDA approval for pain management with spinal cord injury was based on two randomised, double-blind, placebo-controlled Phase III studies that enrolled 357 patients. Lyrica significantly decreased neuropathic pain associated with spinal cord injury from baseline when compared to placebo. Patients treated with Lyrica also experienced a 30% to 50% decrease in pain compared to those who received placebo.
The most common adverse effects in patients receiving Lyrica were somnolence, dizziness, dry mouth, tiredness, and peripheral oedema.