Pharmacologic therapy for fibromyalgia

While nonpharmacologic strategies can help patients understand and accept the diagnosis of fibromyalgia, pharmacologic therapy can provide important additional symptom relief and improvement in functioning. Pharmacologic therapy must be individualized based on a comprehensive evaluation of the patient and continued assessment of symptoms and response to treatment. Patient symptoms and impairments related to each of the dimensions of the "fibromyalgia triad" (pain, sleep dysfunction, and mood disorders) as well as any other comorbidities, past experiences with treatment, and patient preferences should guide therapy selection.     

Comorbidities in chronic neuropathic pain

Neuropathic pain arises from a lesion or dysfunction within the nervous system; the specific mechanisms that elicit neuropathic pain symptoms are the subject of ongoing research. It is generally acknowledged that neuropathic pain is extremely difficult to treat, and a major factor impacting outcomes is the presence of comorbidities such as poor sleep, depressed mood, and anxiety. Patients who suffer from chronic pain experience difficulties in initiating and maintaining sleep. Sleep deprivation has been associated with a decreased pain threshold, muscle aches, and stiffness in normal volunteers. The interrelationship of these factors is complex: Many chronic pain patients are depressed and anxious; sleep deprivation can lead to anxiety; and depression can be both the cause and the result of sleep disturbances. Thus, physicians must evaluate all aspects of pain, sleep, and mood in chronic pain patients. Several instruments have been developed to aid physicians in gathering qualitative and quantitative information from chronic pain patients. This triad of chronic pain, sleep disturbances, and depression/anxiety must be fully addressed if the patient is to be restored to optimal functionality. A multidisciplinary team approach allows for treatment of the whole patient. Nonpharmacologic interventions include relaxation therapy, sleep restriction therapy, and cognitive therapy. Strategies for pharmacologic interventions should attempt to maximize outcomes by employing, where possible, agents that address both the pain and the comorbidities. In this way, functionality may be restored and the patient's quality of life improved.     

Management of psychiatric comorbidity in fibromyalgia

Fibromyalgia is a chronic musculoskeletal pain condition of unknown etiology that predominantly affects women. Lifetime mood and anxiety disorders are common in patients with fibromyalgia and affect the course and severity of fibromyalgia. Recent fibromyalgia clinical trials have included clinical assessments to identify comorbid psychiatric disorders and determine the impact of comorbidity on treatment response. Options for the treatment of fibromyalgia patients with comorbid major depressive disorder or anxiety disorders include antidepressants with dual effects on serotonin and norepinephrine (eg, venlafaxine, duloxetine), which reduce pain in patients with fibromyalgia and have antidepressant and anxiolytic activity. Other possible treatments for anxiety or sleep disturbances associated with fibromyalgia include the alpha-2-delta ligands (eg, pregabalin, gabapentin) that reduce pain in fibromyalgia patients, have anxiolytic effects, and enhance slow-wave sleep. Antidepressants or alpha-2-delta ligands should be combined with established mood stabilizers in patients with comorbid fibromyalgia and bipolar disorder. There is also evidence to support exercise and cognitive-behavioral therapy in the treatment of fibromyalgia and mood or anxiety disorders. Many patients would likely benefit from combinations of pharmacologic and nonpharmacologic treatments.     

Multidisciplinary modalities in the treatment of fibromyalgia

Fibromyalgia is a common musculoskeletal pain condition associated with chronic widespread pain, tenderness at various points on the body, fatigue, and sleep abnormalities. Individuals with fibromyalgia often have comorbid anxiety, depression, and/or other pain syndromes. Research into pharmacologic remedies for fibromyalgia has demonstrated efficacy for a variety of agents, but pharmacology is only one piece of the puzzle when it comes to successful management of fibromyalgia. Sensitive and appropriate methods of diagnosis and an integrated treatment plan including proper patient education, aerobic exercise, and cognitive-behavioral therapy have been shown to be effective in alleviating fibromyalgic symptoms.     

Management of fibromyalgia in primary care

Most treatments for patients with fibromyalgia can be provided in primary care practices. When clinicians, therapists, and community resources work together, a range of pharmacologic and nonpharmacologic treatments can be tailored to provide effective long-term care. Treatments found to be effective for various fibromyalgia symptoms, such as pain and problems with sleep or mood, include antidepressants and anticonvulsants. Additionally, other effective strategies include patient education, light exercise, and cognitive-behavioral therapy.     

Chronic pain and comorbid mood and substance use disorders: A biopsychosocial treatment approach

Chronic pain is a colossal heath care problem that is devastating to the individual afflicted with unremitting pain and frustrating to the beleaguered health care provider attempting to adequately manage this multifaceted disease. The biopsychosocial model of pain management is a promising approach that emphasizes evidence-based medication management in conjunction with cognitive-behavioral therapy and a graded exercise program. The patient with chronic pain and concomitant mood and/or substance use disorders is exceptionally challenging. Effective pharmacologic management of pain and comorbid mood disorders, including the thoughtful use of opioids, can have a dramatic effect in improving the quality of life in patients with chronic pain. The high prevalence of chronic pain in our society and the scarcity of experienced pain medicine physicians necessitate the development of a community-based systems approach to this complex patient population.     

Behavioral management of sleep disturbances secondary to chronic pain

The clinical efficacy of a behavioral management program for treating insomia secondary to chronic pain was evaluated within a multiple-baseline design a across subjects. Treatment consisted of a combination of stimulus control and sleep restriction procedures. Daily sleep diaries and all-night polysomnographic (PSG) measures were used to document changes in sleep/wake patterns. The results showed that treatment was effective in improving sleep patterns in all three patients. A substantial decrease of time awake at night was obtained and this was reflected by reductions of sleep onset latency, wake time after sleep onset, and early morning awakenings. Sleep improvements were well maintained at follow-ups and were also paralleled by improved mood states. The findings indicate that behavioral procedures are effective for treating sleep disturbances associated with chronic pain conditions.     

"Scratching" beneath the surface: an integrative psychosocial approach to pediatric pruritus and pain

Pruritus is prevalent in children with atopic dermatitis and associated with effects on mood, quality of life, sleep, scholastic performance, social and family functioning. In this study a 7-year-old African American female with severe atopic dermatitis, itching and pain refractory to multiple systemic and topical medications was referred for treatment. At baseline, the patient scratched to the point of bleeding, despite maximal doses of anti-histamines, antidepressant and topical therapies. The patient became progressively shy, anxious, and her scholastic performance suffered. A literature review prompted the implementation of a multi-modal program of family cognitive behavioral therapy, imagery, aromatherapy, drawing, and biofeedback. The results were that decreased itch, scratching, pain, and anxiety were seen within the first month. Fewer lesions and episodes of bleeding were observed with almost complete skin clearance by the fourth month. The article concludes that a short-term, integrative program including psychological, complementary and alternative medicine (CAM), and medical therapies may represent a novel, efficacious approach for children suffering from severe atopic dermatitis.     

The relation of sleep difficulties to fatigue, mood and disability in chronic fatigue syndrome

The relationship of sleep complaints to mood, fatigue, disability, and lifestyle was examined in 69 chronic fatigue syndrome (CFS) patients without psychiatric disorder, 58 CFS patients with psychiatric disorder, 38 psychiatric out-patients with chronic depressive disorders, and 45 healthy controls. The groups were matched for age and gender. There were few differences between the prevalence or nature of sleep complaints of CFS patients with or without current DSM-IIIR depression, anxiety or somatization disorder. CFS patients reported significantly more naps and waking by pain, a similar prevalence of difficulties in maintaining sleep, and significantly less difficulty getting off to sleep compared to depressed patients. Sleep continuity complaints preceded fatigue in only 20% of CFS patients, but there was a strong association between relapse and sleep disturbance. Certain types of sleep disorder were associated with increased disability or fatigue in CFS patients. Disrupted sleep appears to complicate the course of CFS. For the most part, sleep complaints are either attributable to the lifestyle of CFS patients or seem inherent to the underlying condition of CFS. They are generally unrelated to depression or anxiety in CFS.     

New treatment options in the management of fibromyalgia: role of pregabalin

Fibromyalgia (FM) is a common, chronic pain disorder with unknown etiology, characterized by widespread musculoskeletal pain and tenderness, and accompanied by several other symptoms such as sleep disturbance, fatigue, and mood disorders. Pregabalin is the first drug approved for the treatment of FM. Pregabalin has analgesic, anticonvulsant, and anxiolytic activity and has earlier demonstrated efficacy in the management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and as adjuvant therapy for adult patients with partial onset seizures. Pregabalin, a lipophilic gamma-aminobutyric acid (GABA) analog, is α₂δ-1 ligand that binds to, and modulates, voltage-gated calcium channels. This modulation is characterized by a reduction of the excessive neurotransmitter release that is observed in certain neurological and psychotic disorders. Several randomized, double-blind, placebo-controlled studies have demonstrated that pregabalin has been effective in pain management, improving sleep quality and fatigue, as well as in several domains of health related quality of life. Because of mild to moderate adverse effects it can be considered a well-tolerated therapy for FM.     

Sleep quality in advanced cancer patients

OBJECTIVE: The objective of this study was to evaluate the sleep quality of advanced cancer patients and its relationship with pain, depression, and hopelessness. METHODS: The participants were 102 advanced cancer patients who were on palliative treatment. Patients completed a sleep quality instrument, the Pittsburgh Sleep Quality Index (PSQI); a pain assessment tool, the Greek Brief Pain Inventory; a self-report measure of depression, the Beck Depression Inventory; and, finally, the Beck Hopelessness Scale. RESULTS: Multiple regression analyses (forward method) have shown that hopelessness (P=.003), "interference of pain with mood" (P<.0005), and strong opioids (P=.010) seemed to influence patients' sleep quality (PSOI). In an additional regression analysis (enter method), the PSQI is significantly related to opioids (P=.013), hopelessness (P=.035), and "interference of pain with mood" (P=.004). CONCLUSION: Hopelessness, pain treatment, and "interference of pain with mood" may influence the quality of sleep in advanced stages of cancer.     

Sleep and pain: interaction of two vital functions

Disturbed sleep is a key complaint of people experiencing acute and chronic pain. These two vital functions, sleep and pain, interact in complex ways that ultimately impact the biological and behavioral capacity of the individual. Polysomnographic studies of patients experiencing acute pain during postoperative recovery show shortened and fragmented sleep with reduced amounts of slow wave and rapid eye movement (REM) sleep, and the recovery is accompanied by normalization of sleep. Objective assessments of sleep in patients with various chronic pain conditions have been less definitive with some studies showing fragmented and shortened sleep and others showing normal sleep. Although daytime fatigue is a frequent complaint associated with complaints of pain-related disturbed sleep, objective assessments of daytime sleepiness reveal minimally elevated levels of sleepiness and emphasize the importance of distinguishing sleepiness and fatigue. The pain-sleep nexus has been modeled in healthy pain-free subjects and the studies have demonstrated the bidirectionality of the sleep-pain relation. Given this bidirectionality, treatment must focus on alleviation of both the pain and sleep disturbance. Few of the treatment studies have done such, and as a result no clear consensus on treatment approaches, much less on differential etiology-based treatment strategies, has emerged.     

Effects of Long-Term Video-electroencephalographic Monitoring on Mood in Epilepsy Patients

This study examines changes in mood of 79 epilepsy patients who completed the Profile of Mood States during long-term video-electroencephalographic monitoring (LTM). Statistical linear models included the effects of age, gender, increased seizure frequency, sleep deprivation, and taper of antiepileptic drugs (AEDs) on mood. Sleep deprivation increased fatigue and decreased vigor from baseline to Day 3, but not from baseline to Day 8 or the final day of the protocol. Taper of AEDs did not adversely affect mood, with removal of phenytoin improving mood. Subjects who had seizures during LTM also improved in mood, becoming less depressed and less fatigued than those who did not have seizures. Overall, our data indicate that LTM does not adversely affect mood. However, in the first few days of LTM, sleep deprivation may produce fatigue and lack of vigor, and should be used only as needed to provoke seizures.     

Nocturnal sleep,daytime sleepiness and fatigue in fibromyalgia patients compared to rheumatoid arthritis patients and healthy controls: A preliminary study

ObjectiveFibromyalgia (FM) and rheumatoid arthritis (RA) are pain disorders, both of which are associated with complaints of sleep disturbance, non-refreshing sleep, and daytime sleepiness and fatigue. Given the putative differential central versus peripheral nervous system involvement in these disorders, subjective and objective measures of nocturnal sleep, daytime sleepiness, fatigue and pain were compared between patient groups and to healthy controls (HC).MethodsFifty women (18 with FM, 16 with RA, and 16 HC) completed an 8 h nocturnal polysomnogram (NPSG), Multiple Sleep Latency Test (MSLT) the following day, and self-reports of sleepiness, fatigue, and pain.ResultsFM and RA patients were similar to each other and had less total sleep time than HC, primarily due to more wake after sleep onset. In an analysis of sleep and wake bouts, both patient groups had longer duration of wake bouts than HC. Nocturnal sleep was judged to be non-restorative for both patient groups. Although reporting the greatest subjective sleepiness and fatigue, FM patients had less objective (MSLT) daytime sleepiness than HC, whereas RA patients were intermediate in objective sleepiness. Unlike the RA and HC, FM patients also showed no association between their subjective and objective sleepiness.ConclusionsWomen with FM have similar nocturnal sleep disturbance as those with RA, but FM patients report greater self-rated daytime sleepiness and fatigue than RA and HC, which did not correspond to the relatively low level of objectively determined daytime sleepiness of FM patients. These findings suggest a generalized hyperarousal state in FM.     

Fatigue and its association with sleep disorders,depressive symptoms and anxiety in patients with multiple sclerosis

Background and purposeThe aetiopathogenesis of fatigue in multiple sclerosis (MS) is not clear. It could be associated with structural changes of the central nervous system, but also with mood and sleep disorders. The purpose of the study was to evaluate frequency of fatigue and its association with sleep and mood disorders in MS patients.Material and methodsThe examined group consisted of 122 MS patients (mean age 37.7 ± 10.8 years). The following questionnaires were used: Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (ESS), Athens Insomnia Scale (AIS), Montgomery-Asberg Depression Rating Scale (MADRS), and Hospital Anxiety and Depression Scale (HADS).ResultsFatigue was present in 75 MS patients (61.5%). Excessive daytime sleepiness was observed in 25 (20.5%), insomnia in 73 patients (59.8%). According to MADRS, depressive symptoms were present in 33 (27%), according to HADS in 15 people (12.3%). Anxiety was present in 32 patients (26.2%). We observed an association between fatigue (FSS) and sleep disorders (ESS, AIS) and also between fatigue and either depression (MADRS, HADS-D) or anxiety (HADS-A). The FSS score was not associated with age, sex, disease course and duration, Expanded Disability Status Stage (EDSS), treatment or level of education in MS patients. In inactive professionally people we noted significantly higher FSS scores (44.8 ± 13.8) in comparison with active individuals (37.2 ± 14.9; p = 0.0053).ConclusionsFatigue is a very common symptom in MS, sometimes associated with sleep disorders, depressive symptoms or anxiety. The treatable causes of fatigue in MS such as sleep and mood disturbances should be identified and treated.     

Sleep deprivation in chronic somatoform pain-effects on mood and pain regulation

Sleep deprivation was found to exert complex effects on affective dimensions and modalities of pain perception both in healthy volunteers and patients with major depression. Considering multifaceted links between mood and pain regulation in patients with chronic somatoform pain, it is intriguing to study sleep deprivation effects for the first time in this group of patients. Twenty patients with a somatoform pain disorder according to ICD-10 diagnostic criteria were sleep-deprived for one night, followed by one recovery night. Clinical pain complaints (visual analog scale), detection- and pain thresholds (temperature and pressure) as well as mood states (Profile of Mood States) were assessed on the day prior to the experiment, on the day after sleep deprivation and on the day after recovery sleep. We found a discrepancy between significantly increased clinical pain complaints and unaltered experimental pain perception after sleep deprivation. Only the clinical pain complaints, but not the experimental pain thresholds were correlated with tiredness-associated symptoms. Total mood disturbances decreased and feelings of depression and anger improved significantly after sleep deprivation. However, these changes were not correlated with a change in clinical pain perception. We conclude that sleep deprivation may generally change the reagibility of the limbic system, but mood processing and pain processing may be affected in an opposite way reflecting neurobiological differences between emotional regulation and interoceptive pain processing.     

Fatigue in obstructive sleep apnea: driven by depressive symptoms instead of apnea severity?

OBJECTIVE: Obstructive sleep apnea is a common and frequently devastating illness that often includes significant fatigue. Fatigue is also a hallmark depressive symptom. The authors wondered if depressive symptoms in patients with obstructive sleep apnea would account for some of the fatigue beyond that explained by obstructive sleep apnea severity. METHOD: Sixty patients with obstructive sleep apnea-i.e., score >/=15 on the respiratory disturbance index (mean score=49; range=15-111)-underwent polysomnography and completed the Center for Epidemiological Studies Depression Scale (CES-D Scale), Profile of Mood States (POMS), and Medical Outcomes Study surveys. Data were analyzed by using hierarchical regression, with POMS fatigue score as the dependent variable (step 1, forced entry of apnea severity variables; step 2, forced entry of CES-D Scale score). RESULTS: Whereas score on the respiratory disturbance index and the percent of time oxygen saturation was <90% together accounted for 4.2% of variance in scores on the POMS fatigue scale, the CES-D Scale score accounted for 10 times the variance (i.e., an additional 42.3%) in POMS fatigue scale score. CONCLUSIONS: After obstructive sleep apnea severity was controlled, higher levels of depressive symptoms were dramatically and independently associated with greater levels of fatigue. Assessment and treatment of mood symptoms-not just treatment of the disordered breathing itself-might reduce the fatigue experienced by patients with obstructive sleep apnea.     

Management of fibromyalgia

Fibromyalgia is characterized by widespread pain, persistent fatigue, nonrestorative sleep, and generalized morning stiffness. The diagnosis is based on patients’ reports of pain and fatigue, clinical findings of multiple tender points, and exclusion of a range of connective tissue and other medical disorders. Treatment of fibromyalgia is multidisciplinary with an emphasis on active patient participation, medications, cognitive behavioral therapy, and physical modalities. No single medication has been found to effectively control all the symptoms, and a rational combination of different medications is often necessary. Currently available medication classes include the selective serotonin uptake inhibitors, the serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, analgesics, hypnotic agents, and anticonvulsants. Treatment modalities should be individualized for patients based on target symptoms and impairment in functioning. As is the case with several chronic disorders, the treatment is often prolonged and improvement may occur slowly. Patience and positive attitude on part of the physician and active involvement of patients and their families in treatment are likely to enhance improvement.     

Temporal relation between sleep and mood in patients with bipolar disorder

BACKGROUND: Early recognition of the prodromal symptoms of bipolar disorder, combined with a patient action plan, may help to prevent relapses. Sleep disturbances are frequent warning signs of both mania and depression. This study used cross correlation analysis to characterize the relationship between mood, sleep and bedrest in longitudinal data. METHODS: Self-reported mood, sleep and bedrest (mean 169 +/- 59 days of data per patient) from 59 outpatients with bipolar disorder receiving standard treatment were analyzed. The cross correlation function was used to determine the latency between the changes in sleep and/or bedrest and mood for time shifts of between -7 and 7 days. RESULTS: For sleep and/or bedrest, a significant inverse correlation was found with the change in mood, most commonly with a time latency of one day. Sleep plus bedrest had the strongest relationship with a change in mood, with a significant correlation in 24 of 59 patients (41%) for the night before or night of a mood change. The patients with a significant cross-correlation between mood and sleep plus bedrest reported about two thirds of all large sleep changes of >3 h and three fourths of all large mood changes (>20 on 100-unit scale). Patients with a significant cross correlation were more likely to take benzodiazepines. CONCLUSION: In most patients with a significant cross correlation between sleep and/or bedrest and mood, the mood change occurred on the day following the change in sleep and/or bedrest. Sleep changes from a previous pattern, especially those of more than 3 h, may indicate that a large mood change is imminent.     

Assessment of the effects of antihistamine drugs on mood,sleep quality,sleepiness, and dream anxiety

Objective. There are limited comparative studies on classic and new-generation antihistamines that affect sleep quality and mood. The purpose of this study was to determine and compare the effects of classic and new-generation antihistamines on sleep quality, daytime sleepiness, dream anxiety, and mood. Methods. Ninety-two patients with chronic pruritus completed study in the dermatology outpatient clinic. Treatments with regular recommended therapeutic doses were administered. The effects of antihistaminic drugs on mood, daytime sleepiness, dream anxiety, and sleep quality were assessed on the first day and 1 month after. Results. Outpatients who received cetirizine and hydroxyzine treatments reported higher scores on the depression, anxiety, and fatigue sub-scales than those who received desloratadine, levocetirizine, and rupatadine. Pheniramine and rupatadine were found to be associated with daytime sleepiness and better sleep quality. UKU side effects scale scores were significantly elevated among outpatients receiving pheniramine. Classic antihistamines increased daytime sleepiness and decreased the sleep quality scores. New-generation antihistamines reduced sleep latency and dream anxiety, and increased daytime sleepiness and sleep quality. Conclusion. Both antihistamines, significantly increased daytime sleepiness and nocturnal sleep quality. Daytime sleepiness was significantly predicted by rupadatine and pheniramine treatment. Cetirizine and hydroxyzine, seem to have negative influences on mood states. Given the extensive use of antihistamines in clinical settings, these results should be more elaborately examined in further studies.