Elena P. Calandre

Cognitive Disturbances and Regional Cerebral Blood Flow Abnormalities in Migraine Patients: Their Relationship with the Clinical Manifestations of the Illness

The purpose of the present study was to evaluate neuropsychological performance and regional cerebral blood flow in migraine patients, and to investigate whether possible abnormalities in any of these fields could be related to the chronicity of the disease. The sample included 60 patients and 30 healthy control subjects; all of them were subjected to a complete neuropsychological assessment, including emotional variables. In addition an interictal 99Tc-HMPAO SPECT was performed in 56 patients and 15 controls. Disturbances in memory, attention and visuomotor speed processing were observed among migraineurs experiencing higher frequency of attacks and in those with a long history of migraine. Anxiety levels were higher in patients than in controls and were positively correlated with attack frequency, but not with cognitive test scores. Brain perfusion abnormalities, mostly hypoperfusion areas, were found in the 43% of patients; poorer performance in two tests, measuring verbal and visual memory, respectively, was found in these patients.

Executive function and decision-making in women with fibromyalgia.

Patients with fibromyalgia (FM) typically report cognitive problems, and they state that these deficits are disturbing in everyday life. Despite these substantial subjective complaints by FM patients, very few studies have addressed objectively the effect of such aversive states on neuropsychological performance. In this study we aimed to examine possible impairment of executive function and decision-making in a sample of 36 women diagnosed with FM and 36 healthy women matched in age, education, and socio-economic status. We contrasted performance of both groups on two measures of executive functioning: the Wisconsin Card Sorting Test (WCST), which assesses cognitive flexibility skills, and the Iowa Gambling Tasks (IGT; original and variant versions), which assess emotion-based decision-making. We also examined the relationship between executive function performance and pain experience, and between executive function and personality traits of novelty-seeking, harm avoidance, reward dependence, and persistence (measured by the Temperament and Character Inventory-Revised). Results showed that on the WCST, FM women showed poorer performance than healthy comparison women on the number of categories and non-perseverative errors, but not on perseverative errors. FM patients also showed altered learning curve in the original IGT (where reward is immediate and punishment is delayed), suggesting compromised emotion-based decision-making; but not in the variant IGT (where punishment is immediate but reward is delayed), suggesting hypersensitivity to reward. Personality variables were very mildly associated with cognitive performance in FM women.

The role of antipsychotics in the management of fibromyalgia.

Fibromyalgia is a syndrome characterized by chronic generalized pain associated with different somatic symptoms, such as sleep disturbances, fatigue, stiffness, balance problems, hypersensitivity to physical and psychological environmental stimuli, depression and anxiety. It has been estimated to affect roughly the 2–4% of the general population in most countries studied, and it has been shown to be much more prevalent in women than in men. Although its pathophysiology is not yet fully understood, it is known that both genetic and environmental factors are involved in its development. Fibromyalgia shares a high degree of co-morbidity with other conditions, including chronic headache, temporomandibular disorder, irritable bowel syndrome, major depression, anxiety disorders and chronic fatigue syndrome. Therefore, this is a syndrome difficult to treat for which multimodal treatments including physical exercise, psychological therapies and pharmacological treatment are recommended. Although different kinds of drugs have been studied for the treatment of fibromyalgia, the most widely used drugs that have the higher degree of evidence for efficacy include the α2δ ligands pregabalin and gabapentin, and the tricyclic antidepressants (TCAs) and serotonin noradrenaline (nor-epinephrine) reuptake inhibitors (SNRIs). However, there is a need to look for newer additional therapeutic pharmacological options for the treatment of this complex and disabling disease.First- and second-generation antipsychotics have shown analgesic properties both in an experimental setting and in humans, although most of the available evidence for the treatment of human pain concerns older antipsychotics and involves clinical trials performed several decades ago. In addition, several second-generation antipsychotics, risperidone, olanzapine and quetiapine, have shown efficacy in the treatment of some anxiety disorders. Some second-generation antipsychotics, mainly quetiapine, aripiprazole and amisulpride, have demonstrated antidepressant activity, with quetiapine approved for the treatment of bipolar depression and refractory major depression, and aripiprazole approved as an adjunctive treatment for major depressive disorder. Finally, several old and new antipsychotics, including promethazine, levopromazine, olanzapine, quetiapine and ziprasidone, have been shown to improve sleep parameters in healthy subjects. Each of these properties suggests that antipsychotics could represent a new potential alternative for the treatment of fibromyalgia syndrome.To date, most of the published studies on the use of antipsychotics in the treatment of fibromyalgia syndrome have been uncontrolled, either case reports or case series, dealing with olanzapine, quetiapine, ziprasidone, levopromazine and amisulpride. The studies on olanzapine and quetiapine have suggested therapeutic efficacy although, in the case of olanzapine, hampered by tolerability problems. A double-blind controlled trial, published in 1980, showed that chlorpromazine increased slow-wave sleep and improved pain and mood disturbances. More recently, four double-blind controlled studies have explored the efficacy of quetiapine, either alone or as an add-on treatment, in fibromyalgia management. None of these trials has yet been published, although two of them have been presented as congress communications, both of them suggesting that quetiapine could be a potential alternative treatment for fibromyalgia.In summary, the current available evidence suggests that at least some antipsychotics, specifically quetiapine, could be useful for the treatment of fibromyalgia and that further studies on the efficacy of these compounds are worth pursuing.

Validation of a Spanish version of the Revised Fibromyalgia Impact Questionnaire (FIQR)

BackgroundThe Revised version of the Fibromyalgia Impact Questionnaire (FIQR) was published in 2009. The aim of this study was to prepare a Spanish version, and to assess its psychometric properties in a sample of patients with fibromyalgia.MethodsThe FIQR was translated into Spanish and administered, along with the FIQ, the Hospital Anxiety Depression Scale (HADS), the 36-Item Short-Form Health Survey (SF-36), and the Brief Pain Inventory (BPI), to 113 Spanish fibromyalgia patients. The administration of the Spanish FIQR was repeated a week later.ResultsThe Spanish FIQR had high internal consistency (Cronbach’s α was 0.91 and 0.95 at visits 1 and 2 respectively). The test-retest reliability was good for the FIQR total score and its function and symptoms domains (intraclass correlation coefficient (ICC > 0.70), but modest for the overall impact domain (ICC = 0.51). Statistically significant correlations (p < 0.05) were also found between the FIQR and the FIQ scores, as well as between the FIQR scores and the remaining scales’ scores.ConclusionsThe Spanish version of the FIQR has a good internal consistency and our findings support its validity for assessing fibromyalgia patients. It might be a valid instrument to apply in clinical and investigational grounds.ResumenAntecedentesEl Cuestionario de Impacto de Fibromialgia (FIQ) ha sido utilizado como medida de valoración en numerosos estudios clínicos. En 2009 se publicó en inglés su versión revisada (FIQR). El presente estudio se llevó a cabo para traducir al español y validar dicha versión.Pacientes y MétodoLa traducción fue realizada por dos de los autores. La versión traducida del FIQR se administró a 113 pacientes con fibromialgia junto con el FIQ, la Escala Hospitalaria de Ansiedad y Depresión, el Cuestionario de Salud SF-36 y la versión abreviada del Cuestionario Breve de Dolor. Una semana después se administró de nuevo el FIQR. Su consistencia interna se evaluó mediante el coeficiente α de Cronbach. Se calcularon los coeficientes de correlación intraclase (ICC) entre las puntaciones de la nueva versión y la anterior, así como las subescalas del Cuestionario SF-36, de la Escala Hospitalaria de Ansiedad y Depresión y del Inventario Breve de Dolor. La fiabilidad test-retest se evaluó igualmente mediante coeficientes de correlación intraclase.ResultadosEl coeficiente α de Cronbach de la versión en estudio fue elevado (0,91 en la primera visita y de 0,95 en la segunda). La fiabilidad test-retest fue buena para la puntuación total del FIQR y para las dimensiones de función y síntomas ( ICC ≥ 0,70) pero modesta para la dimensión de impacto global (ICC = 0,51). Asimismo se encontraron coeficientes de correlación elevados y estadísticamente significativos respecto a las restantes escalas aplicadas (p < 0,05).ConclusiónLa versión española del FIQR es un instrumento válido para su uso en la evaluación e investigación clínicas.

Myofascial trigger points in cluster headache patients: a case series.

Active myofascial trigger points (MTrPs) have been found to contribute to chronic tension-type headache and migraine. The purpose of this case series was to examine if active trigger points (TrPs) provoking cluster-type referred pain could be found in cluster headache patients and, if so, to evaluate the effectiveness of active TrPs anaesthetic injections both in the acute and preventive headaches treatment. Twelve patients, 4 experiencing episodic and 8 chronic cluster headache, were studied. TrPs were found in all of them. Abortive infiltrations could be done in 2 episodic and 4 chronic patients, and preemptive infiltrations could be done in 2 episodic and 5 chronic patients, both kind of interventions being successful in 5 (83.3%) and in 6 (85.7%) of the cases respectively. When combined with prophylactic drug therapy, injections were associated with significant improvement in 7 of the 8 chronic cluster patients. Our data suggest that peripheral sensitization may play a role in cluster headache pathophysiology and that first neuron afferent blockade can be useful in cluster headache management.

An update on pharmacotherapy for the treatment of fibromyalgia

Introduction: Fibromyalgia is a syndrome characterized by chronic generalized pain in addition to different symptoms such as fatigue, sleep disturbances, stiffness, cognitive impairment, and psychological distress. Multidisciplinary treatment combining pharmacological and nonpharmacological therapies is advised. Areas covered: Publications describing randomized controlled trials and long-term extension studies evaluating drug treatment for fibromyalgia were searched in PubMed and Scopus and included in this review. Expert opinion: Different drugs are recommended for the treatment of fibromyalgia by different published guidelines, although only three of them have been approved for this indication by the US FDA, and none have been approved by the European Medicines Agency. According to the available evidence, pregabalin, duloxetine and milnacipran should be the drugs of choice for the treatment of this disease, followed by amitriptyline and cyclobenzaprine. Other drugs with at least one positive clinical trial include some selective serotonin reuptake inhibitors, moclobemide, pirlindole, gabapentin, tramadol, tropisetron, sodium oxybate and nabilone. None of the currently available drugs are fully effective against the whole spectrum of fibromyalgia symptoms, namely pain, fatigue, sleep disturbances and depression, among the most relevant symptoms. Combination therapy is an option that needs to be more thoroughly investigated in clinical trials.

An insight into the gastrointestinal component of fibromyalgia: clinical manifestations and potential underlying mechanisms.

Fibromyalgia syndrome is characterized by chronic generalized pain accompanied by a broad symptomatologic spectrum. Besides chronic fatigue, sleep disturbances, headaches and cognitive dysfunction that are extensively described in the literature, a considerable proportion of patients with fibromyalgia experience gastrointestinal symptoms that are commonly overlooked in the studies that are not specifically dedicated to evaluate these manifestations. Nevertheless, various attempts were undertaken to explore the gastrointestinal dimension of fibromyalgia. Several studies have demonstrated an elevated comorbidity of irritable bowel syndrome (IBS) among patients with fibromyalgia. Other studies have investigated the frequency of presentation of gastrointestinal symptoms in fibromyalgia in a nonspecific approach describing several gastrointestinal complaints frequently reported by these patients such as abdominal pain, dyspepsia and bowel changes, among others. Several underlying mechanisms that require further investigation could serve as potential explanatory hypotheses for the appearance of such manifestations. These include sensitivity to dietary constituents such as gluten, lactose or FODMAPs or alterations in the brain–gut axis as a result of small intestinal bacterial overgrowth or subclinical enteric infections such as giardiasis. The gastrointestinal component of fibromyalgia constitutes a relevant element of the multidisciplinary pathophysiologic mechanisms underlying fibromyalgia that need to be unveiled, as this would contribute to the adequate designation of relevant treatment alternatives corresponding to these manifestations.

Suicidal ideation and the risk of suicide in patients with fibromyalgia: a comparison with non-pain controls and patients suffering from low-back pain

Fibromyalgia is associated with an increased rate of mortality from suicide. In fact, this disease is associated with several characteristics that are linked to an increased risk of suicidal behaviors, such as being female and experiencing chronic pain, psychological distress, and sleep disturbances. However, the literature concerning suicidal behaviors and their risk factors in fibromyalgia is sparse. The objectives of the present study were to evaluate the prevalence of suicidal ideation and the risk of suicide in a sample of patients with fibromyalgia compared with a sample of healthy subjects and a sample of patients with chronic low-back pain. We also aimed to evaluate the relevance of pain intensity, depression, and sleep quality as variables related to suicidal ideation and risks. Logistic regression was applied to estimate the likelihood of suicidal ideation and the risk of suicide adjusted by age and sex. We also used two logistic regression models using age, sex, pain severity score, depression severity, sleep quality, and disease state as independent variables and using the control group as a reference. Forty-four patients with fibromyalgia, 32 patients with low-back pain, and 50 controls were included. Suicidal ideation, measured with item 9 of the Beck Depression Inventory, was almost absent among the controls and was low among patients with low-back pain; however, suicidal ideation was prominent among patients with fibromyalgia (P<0.0001). The risk of suicide, measured with the Plutchik Suicide Risk Scale, was also higher among patients with fibromyalgia than in patients with low-back pain or in controls (P<0.0001). The likelihood for suicidal ideation and the risk of suicide were higher among patients with fibromyalgia (odds ratios of 26.9 and 48.0, respectively) than in patients with low-back pain (odds ratios 4.6 and 4.7, respectively). Depression was the only factor associated with suicidal ideation or the risk of suicide.

Monotherapy or Combination Therapy for Fibromyalgia Treatment

Fibromyalgia is a chronic pain disease whose clinical symptomatology also includes different symptom domains: fatigue, sleep disturbances, morning stiffness, dyscognition, and psychological distress. These associated symptoms usually vary in frequency and intensity from patient to patient. Because the efficacy of monotherapy is limited, more severely affected patients frequently require drug combinations. There is, however, scarce scientific information concerning the benefits and risks of such combinations. To date, only ten studies investigating the efficacy and tolerability of two-drug combinations have been published; some of these studies are old and/or studied drugs that are now known to be of little or no interest in fibromyalgia management. Thus, when polytherapy is considered, therapeutic decisions must be based on data from monotherapy trials and a sound knowledge of the pharmacological profile of each drug. Well-designed clinical trials exploring specific drug combinations selected on the basis of potential additive or synergistic effects should be performed.

Amitriptyline for the treatment of fibromyalgia: a comprehensive review

Fibromyalgia is characterized by chronic generalized pain accompanied by a wide range of clinical manifestations. Most clinical practice guidelines recommend multidisciplinary treatment using a combination of pharmacological and non-pharmacological therapies. The tricyclic antidepressant amitriptyline has been most thoroughly studied in fibromyalgia. Amitriptyline has been evaluated in placebo-controlled studies, and it has served as an active comparator to other therapeutic interventions in the treatment of fibromyalgia. In addition, several systematic reviews and meta-analyses have evaluated its efficacy and safety for the treatment of fibromyalgia. Data from individual studies as well as from systematic reviews indicate that low doses (10–75 mg/day) of amitriptyline are effective for the treatment of fibromyalgia and, despite the limited quality of the data, they do not seem to be associated with relevant tolerability or safety issues. Consistent with some clinical guidelines, we believe amitriptyline in low doses should be considered a first-line drug for the treatment of fibromyalgia.