Prior to the U.S. Food and Drug Administration’s 2007 approval of Lyrica as a treatment for Fibromyalgia, management for the disease was focused on a combination of “off-label” drugs that attempted to addressed its many symptoms including widespread pain, fatigue, sleep problems, anxiety and depression. Since Lyrica’s approval, a considerable amount of research has been conducted evaluating its effectiveness in treating the disease.
Effectiveness of Lyrica
As reported in the full prescribing information for Lyrica, several studies evaluated the efficacy of Lyrica for the management of Fibromyalgia, including a number of randomized, double-blind, placebo-controlled trials, which is considered the “gold standard” design for research studies. The first of these, a 2008 study conducted by Arnold and colleagues, compared three separate total daily doses of Lyrica (300 mg, 450mg, and 600mg) with a placebo (“sugar pill”) in 750 patients with a confirmed diagnosis of Fibromyalgia. Of those who were randomized to receive Lyrica, only 64% completed the study meaning 36% dropped out. The greatest improvements in pain reduction and overall response were found among those patients who received the 450mg/day dose, with 77.8% of patients showing improvement, versus 68.1% for the 300mg/day dose and 66.1% for the 600mg/day dose. The researchers did not find any evidence of an added benefit to the 600mg dose over the 450mg dose. Concurrently, there was an increased risk of side effects at the 600mg dose, including dizziness and sleepiness. For patients who received Lyrica, the study found significant reductions in pain and improvement in overall functioning, with some patients experiencing a decrease in pain as early as one week after starting treatment (Arnold et al., 2008).
The second trial was a multi-phase study that began by establishing the most effective dose for each patient (either 300mg, 450mg, or 600mg/day) over the course of six weeks. Patients who were considered to be responders to treatment were those who had a) a minimum 50% reduction in pain and b) who rated their overall improvement as “much improved” or “very much improved” at the end of the initial six weeks of treatment. At that point, responders were then randomized to continue receiving Lyrica at their current dose or to a placebo for up to six months. The study measured effectiveness by determining how long it took each patient’s response to decline to less than 30% reduction in pain, or by worsening of Fibromyalgia symptoms to the point that an alternative treatment was required. Of the original 1,051 patients enrolled, 54% achieved an effective and tolerable dose during the initial six week period. Of those who continued into the six month follow-up period, the authors found that Lyrica had lasting effects for many, with some patients receiving benefits for up to six months. For the patients who received Lyrica, 38% remained on treatment for 26 weeks, versus only 19% of placebo-treated patients. Of importance to note, however, is the fact that 17% (178 patients) had to discontinue treatment with Lyrica due to adverse side effects (Crofford et al., 2008).
Finally, Mease et al. (2008) studied efficacy and safety of Lyrica in 748 Fibromyalgia patients over the course of 13 weeks. The researchers found that patients who received any of the three doses of Lyrica studied (300mg, 450mg, or 600mg/day) experienced statistically significant improvements in pain when compared to those who received placebo.
Lyrica and Sleep Disturbances
The effects of Lyrica on sleep disturbances have also been evaluated in Fibromyalgia patients. A 2009 study by Russell et al. collected data from two previously-conducted randomized controlled trials: the Arnold et al. (2008) and Mease et al. (2008) studies discussed above. To determine the effects of Lyrica on sleep disturbances, Russell et al. reviewed daily patient diary data, in which each patient reported the quality of their sleep over the previous 24 hour period by rating it on a scale of 0 to 11, with 0 representing “best possible sleep” and 11 representing “worst possible sleep.” Patients in both studies also completed the Medical outcomes Study (MOS) Sleep Scale, which is a 12-item questionnaire that evaluates both initiation and maintenance of sleep. Using a variety of statistical analysis methods, Russell et al. evaluated the sleep data in relation to decreases in pain and overall improvement in functioning. They found that for the Mease et al. study, patients in all three Lyrica dose groups showed significant improvement versus the placebo group with regard to sleep diary scores, and MOS measures of sleep disturbance, quantity of sleep, and sleep problems. All treatment groups also showed improvements in the MOS measures of daytime sleepiness. For the Arnold et al. study, significant improvements were also observed for all three Lyrica dose groups versus the placebo group for both the sleep diary scores and MOS measures of sleep disturbance, quantity of sleep, sleep adequacy, and sleep problems. For both studies, the improvements in sleep diary scores were highly related to overall improvements in pain. Russell et al. concluded their analysis by noting the need for additional research regarding the relationship between pain and sleep dysfunction (Russell et al., 2009).