Mahmoud Slim

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.

Alpha2delta ligands, gabapentin, pregabalin and mirogabalin: a review of their clinical pharmacology and therapeutic use.

ABSTRACT Introduction: The first two alpha2delta ligands – gabapentin (GBP) and pregabalin (PGB) – were initially synthesized as antiepileptics; however, they were later also found to be useful for the treatment of additional conditions. Areas covered: Relevant publications describing potential underlying mechanisms, clinical pharmacokinetics/pharmacokinetics, and clinical efficacy and safety of these drugs in various disease conditions were searched in PubMed and Scopus and included in this review. Expert commentary: GBP and PGB are effective for the treatment neuropathic pain, fibromyalgia and epilepsy; in addition, they may be useful for the reduction of postoperative pain. PGB is also effective for the treatment of generalized anxiety disorder and GBP for the treatment of restless legs syndrome. GBP may be considered a treatment option for pain associated with Guillain-Barré Syndrome and phantom limb and for the management of uremic pruritus. Mirogabalin (MGB), recently developed, is being investigated for the treatment of peripheral neuropathic pain and fibromyalgia, showing promising results in patients with diabetic peripheral neuropathy. Their most frequent adverse reactions are of neuropsychiatric nature and include fatigue, dizziness, sedation, somnolence, and ataxia; peripheral edema and weight gain are also frequently described. Pharmacokinetic interactions are scarce; however, pharmacodynamic interactions have been described in association with drugs with CNS-depressant effects.

Agomelatine for the treatment of patients with fibromyalgia and depressive symptomatology: an uncontrolled, 12-week, pilot study.

INTRODUCTION Agomelatine, a melatonin agonist and selective 5-HT2C antagonist, is a novel antidepressant with sleep-enhancing properties. The purpose of this study was to assess the efficacy and tolerability of agomelatine among patients with fibromyalgia and depression. METHODS 23 patients with fibromyalgia and depressive symptomatology received 25-50 mg of agomelatine daily for 12 weeks. The primary outcome measure was the change of the Beck depression inventory score. Secondary outcome measures included the hospital anxiety and depression scale, Pittsburgh sleep quality index, Fibromyalgia Impact Questionnaire, short-form health survey, brief pain inventory and patients global impression scale. RESULTS Agomelatine significantly improved depression, global fibromyalgia severity and pain intensity but effect sizes were small. No improvement was seen in sleep quality. Patients categorized as responders to treatment had milder disease severity than non-responders. Agomelatine therapy was well tolerated and patients only reported mild and transient side effects. DISCUSSION Agomelatine slightly improved depressive and fibromyalgia symptomatology but did not improve sleep quality. Our data do not support agomelatine as a first-line treatment option for the treatment of fibromyalgia and depression.

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.

The Effects of a Gluten-free Diet Versus a Hypocaloric Diet Among Patients With Fibromyalgia Experiencing Gluten Sensitivity-like Symptoms: A Pilot, Open-Label Randomized Clinical Trial.

Background and Aims: Patients with fibromyalgia frequently present with symptoms similar to those experienced by patients with gluten-related disorders, raising the possibility that a subgroup of these patients could be experiencing underlying gluten sensitivity. This study aimed to evaluate the effects of a gluten-free diet (GFD) compared with a hypocaloric diet (HCD) among patients with fibromyalgia. Methods: Adult patients diagnosed with fibromyalgia were randomly allocated to receive a GFD or a HCD over a 24-week period. The primary outcome measure was the change in the number of gluten sensitivity symptoms. The following secondary outcomes were evaluated: body mass index, Revised Fibromyalgia Impact Questionnaire, Pittsburgh Sleep Quality Index, Brief Pain Inventory, Beck Depression Inventory-II, State-Trait Anxiety Inventory, Short-Form Health Survey, Patient Global Impression Scale of Severity, Patient Global Impression Scale of Improvement, and adverse events. Results: Seventy-five subjects were randomly allocated to receive either a GFD (n=35) or an HCD (n=40). The least squares mean change in the total number of gluten sensitivity symptoms from baseline did not differ significantly between the GFD and HCD groups (−2.44±0.40 for the GFD; −2.10±0.37 for the HCD; P=0.343). Similarly, the 2 dietary interventions did not differ in any of the remaining measured secondary outcomes. Both dietary interventions were well tolerated. Conclusions: Both dietary interventions were associated with similar beneficial outcomes in reducing gluten sensitivity symptoms and other secondary outcomes. However, despite its specificity, GFD was not superior to HCD in reducing the number of gluten sensitivity symptoms or secondary outcomes.

The effects of gluten-free diet versus hypocaloric diet among patients with fibromyalgia experiencing gluten sensitivity symptoms: Protocol for a pilot, open-label, randomized clinical trial

BACKGROUND Fibromyalgia is a chronic musculoskeletal pain syndrome characterized by a broad spectrum of manifestations. Patients with fibromyalgia frequently suffer from manifestations similar to those experienced by patients with gluten-related disorders raising the possibility that some patients with fibromyalgia could suffer from underlying gluten sensitivity. OBJECTIVE This study aims to assess whether avoiding gluten among patients with fibromyalgia and gluten sensitivity is beneficial. METHODS Adult patients with fibromyalgia presenting gluten sensitivity symptoms are randomly allocated to receive gluten-free diet or hypocaloric diet for 24 weeks. The primary outcome measure is the mean change in the number of experienced gluten sensitivity symptoms. Secondary outcome measures include the mean changes in the body mass index, Revised Fibromyalgia Impact Questionnaire, Pittsburgh Sleep Quality Index, Brief Pain Inventory, Beck Depression Inventory-II, State-Trait Anxiety Inventory, Short-Form Health Survey and Patient Global Impression Scale of Severity. Other secondary outcome measures include the frequency of potential adverse events and the proportion of responders according to the Patient Global Impression Scale of Improvement. DISCUSSION Previous studies assessing dietary interventions in fibromyalgia primarily evaluated their effects on the severity and impact of fibromyalgia symptoms and pain. The current study is the first to evaluate the effects of gluten-free diet on the gluten sensitivity symptoms experienced by patients with fibromyalgia. The results of this study will contribute to a better understanding of the potential role of gluten sensitivity in fibromyalgia.

Suicidal behaviors in patients with rheumatic diseases: a narrative review

Chronic rheumatic disorders are characterized by inflammation and chronic pain, and both anxiety and depression have been frequently observed in these patients. Depression and chronic pain are recognized as risk factors for the development of suicidal behaviors. Accordingly, the objective of the present review is to provide a comprehensive review of suicidal behaviors associated with rheumatic diseases. Medline and EMBASE were searched for English language publications using key words related with rheumatic diseases, suicide, suicide attempts, and suicidal ideation. 34 records (30 full-length published papers and 4 studies published in abstract form) that included data related to the frequency and/or potential determinants of suicidal behaviors in rheumatic diseases were included in the review. It was found that both suicidal ideation and completed suicide seem to be more frequent in patients experiencing systemic lupus erythematosus, fibromyalgia and arthritis. Major determinants were comorbid depression in fibromyalgia and arthritis, and neuropsychiatric disease in systemic lupus erythematosus. Based on these findings, suicide risk should be assessed in patients suffering from systemic lupus erythematosus, fibromyalgia and/or arthritis.

Lobular Breast Cancer Metastasis to the Colon, the Appendix and the Gallbladder

Background: Metastases of lobular breast cancer are commonly encountered at the level of lungs, bones, brain and liver, whereas lesions in the gastrointestinal tract are rarely seen. Case Report: A case of a patient with metastases in the right colon and gallbladder originating from an invasive lobular carcinoma is described. Conclusion: Adequate diagnostic procedures should be performed in patients with a history of breast cancer and who show gastrointestinal symptoms to rule out the potential presence of gastrointestinal metastases.

Psychiatric Comorbidity in Children and Adults with Gluten-Related Disorders: A Narrative Review

Gluten-related disorders are characterized by both intestinal and extraintestinal manifestations. Previous studies have suggested an association between gluten-related disorder and psychiatric comorbidities. The objective of our current review is to provide a comprehensive review of this association in children and adults. A systematic literature search using MEDLINE, Embase and PsycINFO from inception to 2018 using terms of ‘celiac disease’ or ‘gluten-sensitivity-related disorders’ combined with terms of ‘mental disorders’ was conducted. A total of 47 articles were included in our review, of which 28 studies were conducted in adults, 11 studies in children and eight studies included both children and adults. The majority of studies were conducted in celiac disease, two studies in non-celiac gluten sensitivity and none in wheat allergy. Enough evidence is currently available supporting the association of celiac disease with depression and, to a lesser extent, with eating disorders. Further investigation is warranted to evaluate the association suggested with other psychiatric disorders. In conclusion, routine surveillance of potential psychiatric manifestations in children and adults with gluten-related disorders should be carried out by the attending physician.

Pelvic floor dysfunction in women with fibromyalgia and control subjects: Prevalence and impact on overall symptomatology and psychosocial function

To evaluate the prevalence, distress, and impact of pelvic floor dysfunction (PFD) symptomatology in women with fibromyalgia and control women. We also aimed to evaluate the impact of PFD symptomatology on several psychosocial measures such as mood, sleep, pain, and quality of life.