A recent cross-sectional study found that several chronobiological variables, including chronotype, circadian rhythm disruption, sleep-wake patterns, and sleep quality may differ between patients with fibromyalgia who responded to serotonin-norepinephrine reuptake inhibitors (SNRIs) and those who did not.
Furthermore, the study identified specific chronobiological factors that predicted nonresponse to SNRI treatment in patients with fibromyalgia.
In the study, published in Rheumatology International, investigators included 60 patients with fibromyalgia (30 SNRI responders and 30 nonresponders) and 30 healthy controls. The participants were assessed using the following questionnaires:
- Composite Scale of Morningness (CSM)
- Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN)
- Sleep-Wake Pattern Assessment Questionnaire (SWPAQ)
- Pittsburgh Sleep Quality Index (PSQI)
- Fibromyalgia Impact Questionnaire (FIQ).
ANOVA analysis and simple logistic regressions were used to examine the relationships between chronological variables and SNRI treatment response.
Fibromyalgia severity was assessed using the Widespread Pain Index (WPI), Symptom Severity Scale (SSS), and Fibromyalgia Severity (FS) scores.
Compared with SNRI responders, the nonresponders experienced:
- Lower morning affect (11.50 vs 14.00, P = .04)
- Lower anytime wakeability (2.27 vs 4.03, P = .013)
- Worse overall (11.40 vs 7.97, P = .002) and subjective (1.70 vs 1.17, P = .008) sleep quality
- Higher circadian rhythm disruptions (55.47 vs 44.97, P < .001)
- Higher sleep disturbances (1.63 vs 1.30, P = .04)
- Higher sleeping medication use (1.80 vs 0.70, P = .003).
SNRI nonresponders had longer fibromyalgia duration (P = .03); higher FIQ total scores (P < .001), SSS scores (P < .001), and FS scores (P = .004); and greater impairment in physical functioning (P < .001), work (P < .001), well-being (P = .015), and pain (P = .02) compared with responders.
Eveningness levels were higher in the patients with fibromyalgia vs controls (6.08 vs 4.87, P = .042) and nonresponders vs controls (6.67 vs 4.87, P = .008). Both responders (7.57, P = .018) and nonresponders (8.03, P = .005) had higher morning lateness compared with controls (5.27).
Nighttime sleepability was lower in the patients with fibromyalgia (4.87, P < .001), responders (5.70, P = .051), and nonresponders (4.03, P < .001) vs controls (7.73). Daytime wakeability was lower in the patients with fibromyalgia (4.15, P < .003) and responders (3.70, P = .003) vs controls (5.97).
Regarding PSQI components, sleep latency, habitual sleep efficiency, sleep disturbances, and sleeping medication use were all significantly worse in the patients with fibromyalgia, responders, and nonresponders compared with controls (all P < .01). Daytime dysfunction was higher in those with fibromyalgia (1.95), responders (1.73), and nonresponders (2.17) vs controls (0.83), all P < .001.
Logistic regression identified the following variables as predictors of SNRI nonresponse:
- Lower morningness (odds ratio [OR] = 0.93, P = .05)
- Lower morning affect (OR = 0.86, P = .03)
- Higher diurnal dysrhythmia (OR = 1.14, P < .001)
- Lower anytime wakeability (OR = 0.76, P = .015)
- Worse overall sleep quality (OR = 1.31, P = .002)
- Worse subjective sleep quality (OR = 2.832, P = .01)
- Higher sleep disturbances (OR = 2.54, P = .043)
- Higher sleeping medication use (OR = 1.9, P = .003)
- Higher daytime dysfunction (OR = 1.971, P = .049).
This study corroborated previous findings associating eveningness, impaired sleep, and circadian disruption with fibromyalgia. Notably, SNRI nonresponders had worse sleep quality, took more sleep medications, and had greater daytime dysfunction than responders.
Morning light therapy, which advances circadian timing, has shown promise in reducing fibromyalgia severity. Psychoeducation and interventions to improve sleep hygiene and regularity should be considered, especially for SNRI nonresponders. Further research into optimizing circadian rhythms as part of fibromyalgia treatment is warranted. These findings suggested that chronobiological factors should be considered when personalizing treatment for patients with fibromyalgia and that interventions targeting circadian rhythms and sleep may improve SNRI effectiveness in nonresponders.
The authors declared no financial and nonfinancial conflicts of interest that would be relevant to the work conducted or reported in this manuscript.