Chronobiological variables predict non-response to serotonin and noradrenaline reuptake inhibitors in fibromyalgia: a cross-sectional study.

Available data shows associations between chronotype, circadian rhythms, sleep quality and fibromyalgia (FM) presentation. However, no studies have explored links between the chronobiological variables and effectiveness of pharmacotherapy. We aimed to assess the chronotypes, circadian rhythms, sleep-wake cycle and sleep quality in FM and their links to treatment response to serotonin and noradrenalin reuptake inhibitors (SNRI). 60 FM patients: 30 responsive to SNRI (FM T[+]), 30 non-responsive to SNRI (FM T[-]) and 30 healthy controls participated. Subjects were assessed by physician and with questionnaire tools: Composite Scale of Morningness, Biological Rhythms Interview of Assessment in Neuropsychiatry, Sleep-Wake Pattern Assessment Questionnaire, Pittsburgh Sleep Quality Index and Fibromyalgia Impact Questionnaire. ANOVA analysis and simple logistic regressions were used to examine the relationships between chronological variables and response to SNRI. FM T[-] vs. FM T[+] presented lower morning affect (11.50[95%CI 9.96-13.04] vs. 14.00[95%CI 12.42-15.57];p=0.04), anytime wakeability (2.27[95%CI 1.4-3.13] vs. 4.03[95%CI 2.99-5.08];p=0.013) worse overall (11.40[95%CI 9.92-12.88] vs. 7.97[95%CI 6.75-9.19];p=0.002) and subjective (1.70[95%CI 1.30-2.01] vs. 1.17[95%CI 0.94-1.39];p=0.008) sleep quality, higher circadian rhythm disruptions (55.47[95%CI 52.32-58.62] vs. 44.97[95%CI 41.31-48.62];p<0.001), sleep disturbances (1.63[95%CI 1.38-1.68] vs. 1.30[95%CI 1.1-1.5];p=0.04), sleeping-medication use (1.80[95%CI 1.27-2.32] vs. 0.70[95%CI 0.28-1.12];p=0.003). Levels of morningness (AIC=82.91,OR=0.93,p=0.05), morning affect (AIC=81.901,OR=0.86,p=0.03) diurnal dysrhythmia (AIC=69.566,OR=1.14,p<0.001), anytime wakeability (AIC=80.307,OR=0.76,p=0.015), overall sleep quality (AIC=74.665, OR=1.31,p=0.002) subjective sleep quality (AIC=79.353, OR=2.832,p=0.01) and disturbances (AIC=82.669,OR=2.54,p=0.043), sleep medication use (AIC=77.017, OR=1.9,p=0.003) and daytime disfunction (AIC=82.908, OR=1.971,p=0.049) were predictors of non-response to SNRI. Chronobiological variables vary between FM T[+] and FM T[-] and are predictors of non-response to SNRI.

Insulin resistance, clinical presentation and resistance to selective serotonin and noradrenaline reuptake inhibitors in major depressive disorder.

BACKGROUND: The understanding of mechanisms underlying non-response to antidepressants is limited. The latest data highlights the role of insulin resistance (IR) in major depressive disorder (MDD) pathophysiology, presentation, and treatment efficacy. This work aimed to assess IR in MDD and explore the relationships between IR, MDD presentation and non-response to selective serotonin and noradrenaline reuptake inhibitors (SNRI). METHODS: 67 MDD individuals: 36 responsive (MDD T[+]), 31 non-responsive (MDD T[-]) to SNRI and 30 healthy controls were recruited. The treatment response criteria were: Clinical Global Impression Scale-Improvement score of 1 or 2 after ≥ 8 weeks of treatment. Participants were assessed by physician and self-report tools measuring depression, anhedonia, anxiety, bipolarity, sleep quality. Blood samples were collected to assess fasting glucose and insulin levels and calculate HOMA-IR (homeostasis model assessment of insulin resistance). RESULTS: MDD T[-] vs. MDD T[+] had significantly higher body mass index, insulin levels, and HOMA-IR. MDD T[-] presented higher levels of depressed mood, appetite/weight changes, loss of interest, energy, overall depressive symptoms, and sleep impairment; some evaluations suggested higher anhedonia and anxiety in MDD T[-] vs. MDD T[+]. Insulin and IR were weakly but significantly correlated with the severity of psychomotor symptoms, energy level, thoughts of death/suicide, self-criticism, appetite/weight, depressed mood symptoms, sleep problems. IR was weakly but significantly correlated with anhedonia. CONCLUSION: IR appears to be linked to depressive symptoms characteristic of the "metabolic" MDD subtype, such as psychomotor changes, energy level, anhedonia, sleep problems, appetite/weight changes, state and trait anxiety, sleep quality, and non-response to SNRI.

Psychological variables associated with resistance to treatment with serotonin and noradrenaline reuptake inhibitors in fibromyalgia.

OBJECTIVE: The treatment of fibromyalgia (FM) often offers only partial pain relief. Among the most effective drugs for FM pain are serotonin and noradrenalin reuptake inhibitors (SNRI). Few studies investigated the affective temperaments and personality features in FM. Our objective was to explore the associations between the affective temperaments, personality traits, schizotypy and response to SNRI treatment in FM. METHODS: 60 FM patients: 30 responsive to SNRI (FM T[+]), 30 non-responsive to SNRI (FM T[-] and 30 healthy controls were recruited. Resistance to SNRI was defined as <30% pain reduction during at least 8-week treatment. Subjects were assessed by physician and filled self-report questionnaires: Temperament Scale of Memphis, Pisa and San Diego- autoquestionnaire, Ten Item Personality Inventory, Oxford-Liverpool Inventory of Feelings and Experiences and Fibromyalgia Impact Questionnaire (FIQ). ANOVA analysis and simple logistic regressions were used to examine the links between psychological variables and lack of response to SNRI. RESULTS: FM T[-] presented higher scores in total FIQ and in physical, work, well-being, pain, fatigue/sleep, stiffness domains than FM T[+]. FM T[-] showed higher levels of: irritable and anxious temperaments, neuroticism, schizotypy than FM T[+]. The levels of depressive, irritable and anxious temperaments, introversion, neuroticism and schizotypy were linked to lack of response to SNRI. CONCLUSIONS: FM T[+] and FM T[-] differ in clinical presentation and psychological features. The levels of affective temperaments, personality and schizotypal traits are associated with lack response to SNRI in FM.

Predictors of treatment response to serotonin and noradrenaline reuptake inhibitors in fibromyalgia.

INTRODUCTION: Fibromyalgia (FM) is often comorbid with anxiety and depression. Serotonin and noradrenaline reuptake inhibitors (SNRIs) are used in the treatment of FM, depression, and anxiety, but they are ineffective in a substantial number of patients. Recently, it has been reported that FM is associated with impaired glucose metabolism. OBJECTIVES: The aim of the study was to explore the associations between insulin resistance, psychiatric comorbidities, and treatment response to SNRIs in patients with FM. PATIENTS AND METHODS: A total of 59 patients with FM and 30 healthy controls (HCs) were recruited. The study patients were classified as treatment­nonresponsive if the SNRI treatment resulted in a reduction in reported pain by less than 30%. All participants were examined by a physician and completed self­report questionnaires. Blood samples were drawn to assess fasting glucose and insulin levels and to calculate the Homeostatic Model Assessment of Insulin Resistance (HOMA­IR) values. Multivariable logistic regression models were constructed to analyze the associations between insulin resistance, psychiatric comorbidies, and the lack of response to treatment with SNRIs. RESULTS: The SNRI nonresponders (FM [T-]) had higher body mass index (BMI), fasting insulin level, and HOMA­IR values than the responders (FM [T+]) and HCs. The FM [T+] patients did not significantly differ from HCs in terms of BMI, levels of fasting glucose and fasting insulin, and HOMA­IR values. Depression, anxiety, and personality disorders were significantly more prevalent in the FM [T-] than in the FM [T+] group. Insulin resistance, depression, anxiety, and personality disorders were identified as the predictors of nonresponse to SNRI treatment. The effect of BMI on the lack of response to SNRIs was fully mediated by insulin resistance. CONCLUSIONS: Increased values of certain clinical and metabolic parameters (BMI, fasting glucose, fasting insulin, HOMA­IR) as well as the presence of psychiatric comorbidities could affect the response to treatment with SNRIs in the patients with FM.