Lyrica (pregabalin)

Published Online: Tuesday, November 1, 2005

Pain has various causes and, at times, may be very difficult to control. Diabetic peripheral neuropathy (DPN) and postherpetic neuralgia (PHN) are among the most poorly controlled forms of pain. DPN is common in long-standing diabetes patients, with a prevalence approaching 50% in those with the disease for >25 years.1,2 PHN generally refers to pain persisting beyond 4 months from the offset of the rash and is common in the elderly population.3 DPN and PHN are both treated with antidepressants, anticonvulsants, tramadol, opioids, and topical capsaicin.4 Unfortunately, data supporting these clinical interventions is often conflicting and limited. Lyrica, manufactured by Pfizer, was recently approved for the treatment of DPN and PHN and as an adjunct for partial seizures.5

Pharmacology

Lyrica is a lipophilic analogue of gamma-aminobutyric acid (GABA) substituted at the 3-position to facilitate diffusion across the blood-brain barrier. Its pharmacologic effects originate at the alpha-2-delta binding site.6 This interaction causes a reduction in depolarization-induced calcium influx at nerve terminals, thus reducing the release of neurotransmitters. Although Lyrica is structurally related to GABA, it does not share pharmacologic properties with GABA. It also lacks activity on benzodiazepine receptors.7

Clinical Trials

The safety and efficacy of Lyrica were evaluated for the treatment of PHN in an 8-week multicenter, randomized, placebo-controlled trial. Patients with PHN (n = 173) were randomized to receive either 600 mg of Lyrica daily (creatinine clearance [CrCl] >60 mL/min) or 300 mg of Lyrica daily (CrCl = 30-60 mL/min). The results showed that Lyrica-treated patients had a greater decrease in pain, compared with placebo. Sleep also improved in patients treated with Lyrica, compared with placebo, as well as Clinical Global Impression scores (P<.0001). Researchers concluded that Lyrica was more effective for relief of pain and sleep interference, and it exhibited a better global improvement than placebo in the treatment of PHN.8

A multicenter, randomized, doubleblind trial compared Lyrica (300 mg/day) with placebo for the treatment of adult patients with DPN over an 8-week period. Inclusion criteria for the study were consistent with DPN diagnosis accepted by the American Diabetes Association. There was a significant reduction in the mean pain score between the Lyrica (2.5) and the placebo (0.8) groups at the end of the study. Investigators found that Lyrica was effective in relieving pain associated with DPN, as well as in improving overall mood, sleep disturbance, and quality of life.9

Three fixed-dose, randomized, double- blind, placebo-controlled, multicenter trials were conducted to evaluate the effectiveness of Lyrica as an adjunct treatment in patients with refractory partial seizures. Polled analysis of these trials reported a 41.3% improvement from baseline in 28-day seizure-free rate.10-12

Safety

The most common adverse effects reported from the trials were dizziness, somnolence, weight gain, peripheral edema, blurred vision, diplopia, headache, ataxia, and gastrointestinal disturbances.8-12 Lyrica is in FDA pregnancy category C.5 Dose adjustment is recommended in patients with CrCl <60 mL/min.6

Outlook

The recommended starting dose of Lyrica is 150 mg daily, given in 3 divided doses, with a maximum dose of 600 mg.5 Lyrica appears to be a valuable addition to the treatment of painful DPN, PHN, and partial seizures. It also is showing promising results in the treatment of generalized anxiety disorder, fibromyalgia, social phobia, and osteoarthritis. It could prove to be very useful in the management of pain, epilepsy, and anxiety disorders.

Drs. Faria and Soo are both senior research pharmacists with the Investigational Drug Service at Brigham and Women's Hospital, Boston, Mass. Dr. Faria also is a senior human research specialist with Partners HealthCare System. Simon Gorelikov is a sixth-year PharmD candidate from Northeastern University currently on clinical clerkship in the Investigational Drug Service at Brigham and Women's Hospital.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.




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