The role of insomnia in the treatment of chronic fatigue

AbstractBackgroundThe definition of Chronic Fatigue Syndrome (CFS) overlaps with definitions of insomnia, but there is limited knowledge about the role of insomnia in the treatment of chronic fatigue.AimsTo test if improvement of insomnia during treatment of chronic fatigue was associated with improved outcomes on 1) fatigue and 2) cortisol recovery span during a standardized stress exposure.MethodsPatients (n=122) with chronic fatigue received a 3.5-week inpatient return-to-work rehabilitation program based on Acceptance and Commitment Therapy, and had been on paid sick leave>8weeks due their condition. A physician and a psychologist examined the patients, assessed medication use, and SCID-I diagnoses. Patients completed self-report questionnaires measuring fatigue, pain, depression, anxiety, and insomnia before and after treatment. A subgroup (n=25) also completed the Trier Social Stress Test for Groups (TSST-G) before and after treatment. Seven cortisol samples were collected during each test and cortisol spans for the TSST-G were calculated.ResultsA hierarchical regression analysis in nine steps showed that insomnia improvement predicted improvement in fatigue, independently of age, gender, improvement in pain intensity, depression and anxiety. A second hierarchical regression analysis showed that improvement in insomnia significantly predicted the cortisol recovery span after the TSST-G independently of improvement in fatigue.ConclusionImprovement in insomnia severity had a significant impact on both improvement in fatigue and the ability to recover from a stressful situation. Insomnia severity may be a maintaining factor in chronic fatigue and specifically targeting this in treatment could increase treatment response

Cognitive behavioral therapy improves physical function and fatigue in mild and moderate chronic fatigue syndrome : A consecutive randomized controlled trial of standard and short interventions

Objective: To study whether standard cognitive behavioral therapy (CBT) and a shorter, interpersonal oriented cognitive behavioral therapy (I-CBT) can improve physical function and fatigue in patients diagnosed with mild to moderate chronic fatigue syndrome (CFS) in a multidisciplinary fatigue clinic. Design: Consecutively 236 participants 18–62 years old meeting the Centre of Decease Control, CDC 1994 criteria, with a subsample also fulfilling the Canadian criteria for CFS, were randomly allocated to one of three groups. Two intervention groups received either 16 weeks of standard CBT or 8 weeks of I-CBT vs. a waiting-list control group (WLC). Primary outcome was the subscale Physical Function (PF) from SF-36 (0–100). Secondary outcome was amongst others fatigue measured by Chalder Fatigue Questionnaire (CFQ) (0–33). Outcomes were repeatedly measured up to 52 weeks from baseline. Results: The additional effect relative to baseline at post-intervention for SF-36 physical function was 14.2 (95% CI 7.9–20.4 p < 0.001) points higher for standard CBT and 6.8 (0.5–13.2 p = 0.036) points higher for I-CBT compared with the control group. The additional effect relative to baseline at post-intervention for fatigue was 5.9 (95% CI 0.5–10.5 p = 0.03) points lower for standard CBT compared with the control group but did not differ substantially for I-CBT 4.8 (95% CI −0.4 to 9.9 p = 0.07). The positive change in physical function persisted at 1-year follow-up for both treatment groups, and for standard CBT also in fatigue. The two intervention groups did not differ significantly in self-reported physical function and fatigue at the 1-year follow-up. No serious adverse reactions were recorded in any of the groups during the trial period. Interpretation: A 16-week standard, individual CBT intervention improves physical function and fatigue in CFS outpatients with mild to moderate disease. A shorter 8-week I-CBT program improves physical function. Both treatments are safe, and the effect persist 1 year after baseline. Clinical Trial registration: ClinicalTrials.gov, Identifier: NCT00920777, registered June 15, 2009.publishedVersio

The Relationship Between Improvement in Insomnia Severity and Long-Term Outcomes in the Treatment of Chronic Fatigue

Background: The current treatments of choice for patients with chronic fatigue are moderately effective. One way to advance treatments is identifying process variables associated with good treatment outcomes. There is little knowledge regarding a possible association between insomnia and long-term outcomes in the treatment of chronic fatigue.Aims: Testing whether (1) improvement in insomnia is associated with improvement in levels of fatigue at 1-year follow-up, and (2) if such a relationship remains when controlling for improvement in levels of anxiety and depression, and pain in patients with chronic fatigue.Methods: Patients having been on sick leave 8 weeks or more due to chronic fatigue were referred to a return-to-work program. They received an intensive 3.5-week inpatient treatment program based on acceptance and commitment therapy (ACT). Before treatment and at 1-year follow-up the patients completed questionnaires assessing levels of insomnia severity, pain, anxiety and depression, and fatigue.Results: A regression analysis found that changes in insomnia-severity were associated with changes in fatigue-levels at 1-year follow-up. When changes in levels of anxiety and depression were entered in the regression analysis, anxiety and depression was significantly associated with levels of fatigue but insomnia was not. The association between anxiety and depression and fatigue was at a trend level when pain was entered into the model.Conclusion: Long-term improvement in insomnia severity was significantly associated with long-term improvement in chronic fatigue, but not independently of long-term improvement in anxiety and depression, and pain.Trial Registration:https://clinicaltrials.gov/, identifier NCT01568970

Day-to-day variations during clinical drug monitoring of morphine, morphine-3-glucuronide and morphine-6-glucuronide serum concentrations in cancer patients. A prospective observational study

BACKGROUND: The feasibility of drug monitoring of serum concentrations of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) during chronic morphine therapy is not established. One important factor relevant to drug monitoring is to what extent morphine, M6G and M3G serum concentrations fluctuate during stable morphine treatment. METHODS: We included twenty-nine patients admitted to a palliative care unit receiving oral morphine (n = 19) or continuous subcutaneous (sc) morphine infusions (n = 10). Serum concentrations of morphine, M6G and M3G were obtained at the same time on four consecutive days. If readmitted, the patients were followed for another trial period. Day-to-day variations in serum concentrations and ratios were determined by estimating the percent coefficient of variation (CV = (mean/SD) ×100). RESULTS: The patients' median morphine doses were 90 (range; 20–1460) mg/24 h and 135 (range; 30–440) mg/24 h during oral and sc administration, respectively. Intraindividual fluctuations of serum concentrations estimated by median coefficients of day-to-day variation were in the oral group for morphine 46%, for M6G 25% and for M3G 18%. The median coefficients of variation were lower in patients receiving continuous sc morphine infusions (morphine 10%, M6G 13%, M3G 9%). CONCLUSION: These findings indicate that serum concentrations of morphine and morphine metabolites fluctuate. The fluctuations found in our study are not explained by changes in morphine doses, administration of other drugs or by time for collection of blood samples. As expected the day-to-day variation was lower in patients receiving continuous sc morphine infusions compared with patients receiving oral morphine

Metacognitions are associated with subjective memory problems in patients with chronic fatigue

Background: Subjective cognitive impairments are frequent, but poorly understood in patients with chronic fatigue. We hypothesized that maladaptive metacognitive beliefs at baseline were associated with baseline subjective cognitive impairments, that they predict subjective cognitive impairments at treatment termination, and that a reduction in maladaptive metacognitive beliefs was associated with less subjective cognitive impairments at treatment termination, independent of changes in fatigue, pain, insomnia, depression, and anxiety.Methods: In this non-controlled study, patients (n=137) on sick leave due to chronic fatigue received a 3.5-week inpatient RTW rehabilitation program. Of these patients 69 (50.4 %) was referred with a ICPC-2 diagnosis of chronic fatigue. Patients completed questionnaires about metacognitive beliefs, somatic complaints, psychological complaints, and cognitive impairments before and after treatment. To test the hypotheses we performed paired t tests of change, as well as seven hierarchical linear regressions.Results: Results showed that baseline maladaptive metacognitive beliefs were significantly associated with subjective cognitive impairments at baseline, controlling for symptoms. Score on baseline metacognitive beliefs did not predict impairments post-treatment. Testing specific maladaptive beliefs, pre-treatment scores on cognitive confidence were associated with subjective cognitive impairments both pre and post-treatment, controlling for symptoms. Post-treatment metacognitive beliefs and post-treatment cognitive confidence were associated with post-treatment subjective cognitive impairments, controlling for pre-treatment impairments and pre-treatment metacognitive beliefs, as well as pre and post scores on symptom measures. Conclusion: This study reports associations between maladaptive metacognitive beliefs and subjective cognitive impairments in patients with chronic fatigue. Targeting metacognitive beliefs could prove an effective therapeutic intervention for subjective cognitive impairments in these patients

Prevalence of use of non-prescription analgesics in the Norwegian HUNT3 population: Impact of gender, age, exercise and prescription of opioids

Background There are concerns about potential increasing use of over-the-counter (OTC) analgesics. The aims of this study were to examine 1) the prevalence of self-reported use of OTC analgesics; 2) the prevalence of combining prescription analgesics drugs with OTC analgesics and 3) whether lifestyle factors such as physical activity were associated with prevalence of daily OTC analgesic use. Methods Questionnaire data from the Nord–Trøndelag health study (HUNT3, 2006–08), which includes data from 40,000 adult respondents. The questionnaire included questions on use of OTC analgesics, socioeconomic conditions, health related behaviour, symptoms and diseases. Data were linked to individual data from the Norwegian Prescription Database. A logistic regression was used to investigate the association between different factors and daily use of paracetamol and/or non-steroid anti-inflammatory drugs (NSAIDs) in patients with and without chronic pain. Results The prevalence of using OTC analgesics at least once per week in the last month was 47%. Prevalence of paracetamol use was almost 40%, compared to 19% and 8% for NSAIDs and acetylsalicylic acid (ASA), respectively. While the use of NSAIDs decreased and the use of ASA increased with age, paracetamol consumption was unaffected by age. Overall more women used OTC analgesics. About 3-5% of subjects using OTC analgesics appeared to combine these with the same analgesic on prescription. Among subjects reporting chronic pain the prevalence of OTC analgesic use was almost twice as high as among subjects without chronic pain. Subjects with little physical activity had 1.5-4 times greater risk of daily use of OTC compared to physically active subjects. Conclusions Use of OTC analgesics is prevalent, related to chronic pain, female gender and physical inactivity

The Natural Course of Chronic Pain in a General Population: Stability and Change in an Eight-Wave Longitudinal Study Over Four Years (the HUNT Pain Study).

Epidemiological studies have to a little extent addressed the potential fluctuations of chronic pain over time, and there is a lack of information about the long-term course of pain using repeated measurements. We wanted to identify different trajectories of pain during 8 waves of follow-up over 4 years among individuals in the general population reporting pain lasting at least 6 months at baseline. Secondarily, we wanted to investigate whether biopsychosocial factors at baseline were associated with the different pain trajectories. Longitudinal Latent Class Analysis was performed to classify a random sample of 1905 participants from a larger population-based study (HUNT3) into groups based on their longitudinal pain severity reporting. A five-class solution gave the best fit. The terms chosen to describe the pain trajectories were: “fluctuating” (n = 586 [31%]), “persistent mild” (n = 449 [24%]), “persistent moderate” (n = 414 [22%]), “persistent severe” (n = 251 [13%]), and “gradual improvement” (n = 205 [11%]). In a multinomial logistic regression model using “gradual improvement” as the reference category, the “persistent moderate”, “persistent severe”, and “fluctuating” pain groups were associated with chronic widespread pain, elevated levels of catastrophizing, and poorer mental health. The “persistent mild” group was associated with sleep difficulties only. This study finds that although most individuals have a stable pain course, individuals in the largest distinct trajectory reports pain that fluctuate between mild and moderate levels, thus fluctuating under and above the chronic pain definition using moderate pain or more as a criterion

Subjective memory complaints among patients on sick leave are associated with symptoms of fatigue and anxiety

Abstract: Objective: The aim of this study was to identify symptoms associated with subjective memory complaints among subjects who are currently on sick leave due to symptoms of chronic pain, fatigue, depression, anxiety and insomnia. Methods: This was a cross-sectional study, subjects (n = 167) who were currently on sick leave were asked to complete an extensive survey consisting of the following: items addressing their sociodemographics, one item from the SF-8 health survey measuring pain, Chalder Fatigue Questionnaire, Hospital Anxiety and Depression Scale, Insomnia Severity Index and Everyday Memory Questionnaire – Revised. General linear modeling (GLM) was used to analyze variables associated with SMCs. Results: Symptoms of fatigue (p-value <= 0.001) and anxiety (p-value = 0.001) were uniquely and significantly associated with perceived memory failures. The associations with symptoms of pain, depression and insomnia were not statistically significant. Conclusions: Subjective memory complaints should be recognized as part of the complex symptomatology among patients who report multiple symptoms, especially in cases of fatigue and anxiety. Self-report questionnaires measuring perceived memory failures may be a quick and easy way to incorporate and extend this knowledge into clinical practice

Longitudinal associations between exercise and pain in the general population--the HUNT pain study.

BACKGROUND: Population-based studies have reported conflicting findings on the relationship between physical activity and pain, and most studies reporting a relationship are cross sectional. Temporal relationships are therefore difficult to infer and associations may be subject to confounding from a variety of other factors. The aim of the current study was to investigate the association between exercise and pain longitudinally and to use within subjects analyses to remove between subjects confounding. METHODS: In the population-based HUNT 3 study, participants reported both pain and level of exercise. A random sub-sample of 6419 participants was in addition invited to report their last week pain and exercise every three months over a 12 month period (five measurements in total). We used multilevel mixed effects linear regression analyses to prospectively estimate the association between regular levels of exercise (measured in HUNT 3) and subsequent longitudinal reporting of pain. We also estimated within-subjects associations (i.e. the variation in pain as a function of variation in exercise, over time, within individuals) to avoid confounding from between subject factors. RESULTS: Among those invited to participate (N = 6419), 4219 subjects returned at least two questionnaires. Compared with subjects who reported no or light exercise, those who reported moderate levels of exercise or more at baseline, reported less pain in repeated measures over a 12 month period in analyses adjusted for age, sex,education and smoking. Adjusting for baseline level of pain distinctly attenuated the findings. Within subjects, an increase in exercise was accompanied by a concurrent reduction in intensity of pain. However, we found no indication that exercise level at one occasion was related to pain reporting three months later. CONCLUSION: This longitudinal population-based study indicates that exercise is associated with lower level of pain and that this association is close in time

Metacognitions Are Associated with Subjective Memory Problems in Individuals on Sick Leave due to Chronic Fatigue

Background: Subjective cognitive impairments are frequent, but poorly understood in patients with chronic fatigue. We hypothesized that maladaptive metacognitive beliefs at baseline were associated with baseline subjective cognitive impairments, that they predict subjective cognitive impairments at treatment termination, and that a reduction in maladaptive metacognitive beliefs was associated with less subjective cognitive impairments at treatment termination, independent of changes in fatigue, pain, insomnia, depression, and anxiety. Methods: In this non-controlled study, patients (n = 137) on sick leave due to chronic fatigue received a 3.5-week inpatient RTW rehabilitation program. Of these patients 69 (50.4%) was referred with a ICPC-2 diagnosis of chronic fatigue. Patients completed questionnaires about metacognitive beliefs, somatic complaints, psychological complaints, and cognitive impairments before and after treatment. To test the hypotheses we performed paired t-tests of change, as well as seven hierarchical linear regressions. Results: Results showed that baseline maladaptive metacognitive beliefs were significantly associated with subjective cognitive impairments at baseline, controlling for symptoms. Score on baseline metacognitive beliefs did not predict impairments post-treatment. Testing specific maladaptive beliefs, pre-treatment scores on cognitive confidence were associated with subjective cognitive impairments both pre and post-treatment, controlling for symptoms. Post-treatment metacognitive beliefs and post-treatment cognitive confidence were associated with post-treatment subjective cognitive impairments, controlling for pre-treatment impairments and pre-treatment metacognitive beliefs, as well as pre and post-scores on symptom measures. Conclusion: This study reports associations between maladaptive metacognitive beliefs and subjective cognitive impairments in patients with chronic fatigue. Targeting metacognitive beliefs could prove an effective therapeutic intervention for subjective cognitive impairments in these patients