This is the first international study that evaluated the efficacy and safety of SXB in a large number of fibromyalgia patients. The rationale for using SXB was based on its ability to improve restorative sleep and the observation that disturbed sleep can cause hyperalgesia in chronic pain conditions by dysregulation of the descending pain inhibitory pathways.31
It was hypothesised that the attainment of restorative sleep in SXB-treated patients should lead to a reduction in fibromyalgia-related pain and other symptoms by restoring a more normal balance in these pathways, which are known to be dysfunctional in fibromyalgia.32
The improvement in sleep quality as reflected by changes in JSS (a validated measure for sleep quality in the fibromyalgia population)24
and the improvement in ‘tired upon awakening’, one of the items in the FIQ that assesses sleep disturbance, suggest that SXB may improve restorative sleep in fibromyalgia patients. In addition, SXB treatment resulted in a statistically significant reduction in pain and fatigue with both SXB dose groups compared with placebo. Reductions in pain were demonstrated at 30% or greater and at 50% or greater and, in the SXB 6 g/night group, at 80% or greater pain reduction. Particularly for those patients experiencing higher levels of pain reduction, these findings represent clinically important changes that extend beyond pain reduction and encompass a broad range of symptoms. The onset of pain reduction occurred relatively rapidly and was maintained during the 14-week trial in most patients. Tenderness, reflecting hyperalgesia and allodynia, a core domain to be assessed in all fibromyalgia clinical trials,10
was decreased, as seen by a statistically significant reduction in MTPS.
Improvement was not limited to pain, as multiple symptoms and general health, measured by the FIQ total score and SF-36, were also improved. A reduction of 14% or greater in FIQ, achieved by 62.6–70.8% of the SXB groups, is consistent with the MCID definition,33
whereas the reduction of 30% or greater in FIQ achieved by 50.0–55.1% of the SXB groups can be considered a moderate/good response. Moreover, the fibromyalgia syndrome composite score, which is a more stringent measure that includes pain, FIQ and PGIC, was significantly improved for both SXB 4.5 g/night and SXB 6 g/night versus placebo. In addition, a significant improvement in the functional composite score following both SXB doses versus placebo was observed, even when it was based on a more stringent cut-off value for the SF-36 (≥6; as established for fibromyalgia patients)30
than the MCID (3–5).34
The estimated NNT for 50% or greater pain reduction for SXB 4.5 g/night and SXB 6 g/night, 8 and 5, respectively, compare favourably with an NNT of 6.4 for duloxetine (combined 60 and 120 mg doses) for a similar treatment period (12–13 weeks)35
and are superior to the NNT of 16 for pregabalin 450 mg (the maximum recommended dose) for a 12-week treatment period.36
This study is also the first to evaluate NNT for the improvement of multidimensional function (FIQ) and shows that four to six patients need to be treated to achieve clinically relevant improvements.
Several study limitations should be noted. There was a high rate of discontinuation; however, discontinuations in the current study were consistent with the 33–42% discontinuation rate in other fibromyalgia phase 3 clinical trials.19
Another limitation, common to all clinical trials, is that the evaluated population may not necessarily be representative of clinical practice. Demographically, the characteristics of patients in the current study were what may be expected clinically43
and were comparable to study populations in clinical trials for the approved fibromyalgia agents (predominantly female, middle aged, Caucasian, overweight and with fibromyalgia symptoms for approximately 10 years).30
The results from this study, demonstrating the association of sleep quality restoration with the multidimensional improvements in fibromyalgia symptoms, are consistent with the long-held notion that non-restorative sleep may play a role in the pathophysiology of fibromyalgia12
and reinforce the recommendation that the restoration of sleep quality should be a therapeutic aim in fibromyalgia.10
However, this is a challenging goal as many current treatments, such as hypnotics and antidepressants, improve insomnia but may have limited effect on sleep quality and, in particular, non-refreshed sleep.45
It is possible that SXB may improve fibromyalgia symptoms by other as yet unidentified mechanisms, aside from an improvement in sleep quality. Further analysis and mechanistic studies will be required to explore these possibilities.