pregabalin and Syndrome

Fibromyalgia is a clinically defined chronic condition of unknown etiology characterized by chronic widespread pain that often co-exists with sleep disturbances, cognitive dysfunction and fatigue. People with fibromyalgia often report high disability levels and poor quality of life. Drug therapy, for example, with serotonin and noradrenaline reuptake inhibitors (SNRIs), focuses on reducing key symptoms and improving quality of life. This review updates and extends the 2013 version of this systematic review.. To assess the efficacy, tolerability and safety of serotonin and noradrenaline reuptake inhibitors (SNRIs) compared with placebo or other active drug(s) in the treatment of fibromyalgia in adults.. For this update we searched CENTRAL, MEDLINE, Embase, the US National Institutes of Health and the World Health Organization (WHO) International Clinical Trials Registry Platform for published and ongoing trials and examined the reference lists of reviewed articles, to 8 August 2017.. We selected randomized, controlled trials of any formulation of SNRIs against placebo or any other active treatment of fibromyalgia in adults.. Three review authors independently extracted data, examined study quality, and assessed risk of bias. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 50% or greater and of 30% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardized mean differences (SMD) for fatigue, sleep problems, health-related quality of life, mean pain intensity, depression, anxiety, disability, sexual function, cognitive disturbances and tenderness. For tolerability we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawals due to adverse events and for nausea, insomnia and somnolence as specific adverse events. For safety we calculated NNTH for serious adverse events. We undertook meta-analysis using a random-effects model. We assessed the evidence using GRADE and created a 'Summary of findings' table.. We added eight new studies with 1979 participants for a total of 18 included studies with 7903 participants. Seven studies investigated duloxetine and nine studies investigated milnacipran against placebo. One study compared desvenlafaxine with placebo and pregabalin. One study compared duloxetine with L-carnitine. The majority of studies were at unclear or high risk of bias in three to five domains.The quality of evidence of all comparisons of desvenlafaxine, duloxetine and milnacipran versus placebo in studies with a parallel design was low due to concerns about publication bias and indirectness, and very low for serious adverse events due to concerns about publication bias, imprecision and indirectness. The quality of evidence of all comparisons of duloxetine and desvenlafaxine with other active drugs was very low due to concerns about publication bias, imprecision and indirectness.Duloxetine and milnacipran had no clinically relevant benefit over placebo for pain relief of 50% or greater: 1274 of 4104 (31%) on duloxetine and milnacipran reported pain relief of 50% or greater compared to 591 of 2814 (21%) participants on placebo (risk difference (RD) 0.09, 95% confidence interval (CI) 0.07 to 0.11; NNTB 11, 95% CI 9 to 14). Duloxetine and milnacipran had a clinically relevant benefit over placebo in patient's global impression to be much or very much improved: 888 of 1710 (52%) on duloxetine and milnacipran (RD 0.19, 95% CI 0.12 to 0.26; NNTB 5, 95% CI 4 to 8) reported to be much or very much improved compared to 354 of 1208 (29%) of participants on placebo. Duloxetine and milnacipran had a clinically relevant benefit compared to placebo for pain relief of 30% or greater. RD was 0.10; 95% CI 0.08 to 0.12; NNTB 10, 95% CI 8 to 12. Duloxetine and milnacipran had no clinically relevant benefit for fatigue (SMD -0.13, 95% CI -0.18 to -0.08; NNTB 18, 95% CI 12 to 29), compared to placebo. There were no differences between either duloxetine or milnacipran and placebo in reducing sleep problems (SMD -0.07; 95 % CI -0.15 to 0.01). Duloxetine and milnacipran had no clinically relevant benefit compared to placebo in improving health-related quality of life (SMD -0.20, 95% CI -0.25 to -0.15; NNTB 11, 95% CI 8 to 14).There were 794 of 4166 (19%) participants on SNRIs who dropped out due to adverse events compared to 292 of 2863 (10%) of participants on placebo (RD 0.07, 95% CI 0.04 to 0.10; NNTH 14, 95% CI 10 to 25). There was no difference in serious adverse even. The update did not change the major findings of the previous review. Based on low- to very low-quality evidence, the SNRIs duloxetine and milnacipran provided no clinically relevant benefit over placebo in the frequency of pain relief of 50% or greater, but for patient's global impression to be much or very much improved and in the frequency of pain relief of 30% or greater there was a clinically relevant benefit. The SNRIs duloxetine and milnacipran provided no clinically relevant benefit over placebo in improving health-related quality of life and in reducing fatigue. Duloxetine and milnacipran did not significantly differ from placebo in reducing sleep problems. The dropout rates due to adverse events were higher for duloxetine and milnacipran than for placebo. On average, the potential benefits of duloxetine and milnacipran in fibromyalgia were outweighed by their potential harms. However, a minority of people with fibromyalgia might experience substantial symptom relief without clinically relevant adverse events with duloxetine or milnacipran.We did not find placebo-controlled studies with other SNRIs than desvenlafaxine, duloxetine and milnacipran.

Topics: Adrenergic Uptake Inhibitors; Adult; Carnitine; Cyclopropanes; Desvenlafaxine Succinate; Duloxetine Hydrochloride; Fibromyalgia; Humans; Milnacipran; Norepinephrine; Pregabalin; Quality of Life; Selective Serotonin Reuptake Inhibitors; Syndrome

There have been substantial advances in the pharmacotherapy of fibromyalgia (FM), which have occurred in parallel with advances in our understanding of the pathophysiology of FM in the past several years. Consortia of researchers have established a core set of symptom domains, which constitute the condition of FM, including pain, fatigue, sleep and mood disturbance and cognitive dysfunction, which significantly impact a patient's overall well-being and ability to function. Outcome measures, which assess these domains, both singly and in composite format, are showing increasing reliability to discriminate between the treatment and placebo arms in clinical trials of emerging therapies, which are targeting the pathophysiologic mechanisms of FM. Several different medications, including the serotonin and norepinephrine reuptake inhibitors, duloxetine and milnacipran, and the α(2)δ modulator, pregabalin, have been approved by the Food and Drug Administration (FDA) for the management of FM, based on their clinically meaningful and durable effect on pain in monotherapy trials. They also have been shown to beneficially effect patient global impression of change, function and variably other key symptom domains, such as fatigue, sleep disturbance and cognition. Other medicines, although they have not gone through the formal approval process, have also shown efficacy in multiple domains of FM. Although combination trials have generally not yet been performed, the combined use of medicines with complementary mechanisms of action is rational, and, when done with appropriate caution, will likely be shown to be safe and well tolerated. Adjunctive therapy with medicines targeted at specific symptom domains, such as sleep, as well as treatments aimed at common co-morbid conditions, such as irritable bowel syndrome, or disease states, such as rheumatoid arthritis, should be considered for the purpose of reducing the patient's overall symptom burden. Current therapies neither completely treat FM symptoms nor benefit all patients; thus, further research on new therapies with different mechanisms and side-effect profiles is needed.

Topics: Analgesics; Chronic Pain; Clinical Trials as Topic; Cognition Disorders; Cyclopropanes; Duloxetine Hydrochloride; Fatigue; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Milnacipran; Mood Disorders; Pain Management; Pregabalin; Selective Serotonin Reuptake Inhibitors; Sleep Wake Disorders; Syndrome; Thiophenes; Treatment Outcome

Chronic pain in fibromyalgia patients, together with its associated symptoms and co-morbidities, is now considered a result of dysregulated mechanisms in the central nervous system (CNS). As fibromyalgia patients often report sleep problems, the physiological processes that normally regulate sleep may be disturbed and overlap with other CNS dysfunctions. Although the mechanisms potentially linking chronic widespread pain, sleep alterations and mood disorders have not yet been proven, polysomnography findings in patients with fibromyalgia and non-restorative sleep and their relationships with clinical symptoms support the hypothesis of a conceptual common mechanism called 'central sensitisation'. Food and Drug Administration (FDA)-approved drugs for the treatment of fibromyalgia may benefit sleep, but their label does not include the treatment of fibromyalgia-associated sleep disorders. Non-pharmacological therapies (including a thorough sleep assessment) can be considered in the first-line treatment of non-restorative sleep, although they have not yet been fully investigated in patients with fibromyalgia. Both pharmacological and non-pharmacological treatments should be used cautiously in patients with fibromyalgia, bearing in mind the patients' underlying disorders and the potential interactions of the therapies.

Topics: Analgesics; Central Nervous System Sensitization; Chronic Pain; Cyclopropanes; Duloxetine Hydrochloride; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Milnacipran; Physical Therapy Modalities; Polysomnography; Pregabalin; Selective Serotonin Reuptake Inhibitors; Sleep; Sleep Wake Disorders; Syndrome; Thiophenes

Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain and accompanied by a variety of other symptoms such as fatigue, sleep dysfunction, depression, anxiety and cognitive disturbance. Current guidelines recommend tricyclic antidepressants or SSRIs (selective serotonin reuptake inhibitors) as first-line therapies to treat the multiple symptom domains. Until recently, however, there were no licensing authority approved treatments for FMS. The alfa 2 delta modulator pregabalin has anxiolytic, anticonvulsant and antinociceptive properties which has prompted its investigation in FMS. In a series of short-term randomized, double-blind, placebo-controlled trials of 8-14 weeks duration, pregabalin proved effective in reducing the pain and accompanying symptoms of FMS and improved quality of life domains. A 6-month double-blind, placebo-controlled trial demonstrated the durability of its effects on pain and a variety of secondary measures such as fatigue and sleep disturbance. Overall, pregabalin was well tolerated with no new adverse events emerging that have not been reported with its use in other indications.

Topics: Anticonvulsants; Anxiety Disorders; Cognition Disorders; Depression; Fatigue; Fibromyalgia; gamma-Aminobutyric Acid; Humans; Pain; Pregabalin; Quality of Life; Sleep Wake Disorders; Syndrome

We report about a man in his mid-50s who was prescribed pregabalin (150 mg/day) for neuropathic pain due to a herniated intervertebral disc. Four weeks later, he presented to the emergency room with symptoms consistent with delirium. After ruling out acute intoxication with a substance and neurological causes, collateral information from the family and review of his medical chart indicated potential discontinuation syndrome owing to pregabalin. Following the successful treatment and resolution of delirium, the patient revealed he had been consistently consuming pregabalin doses upwards of 2 g/day over the past 2 weeks, leading to the premature exhaustion of his prescription and an abrupt cessation. The case findings underscore the necessity for physicians to recognise the potential for pregabalin misuse and the associated withdrawal risks, including delirium.

Topics: Delirium; Humans; Male; Neuralgia; Pregabalin; Substance-Related Disorders; Syndrome

Topics: Adult; Analgesics; Facial Pain; Female; Humans; Male; Middle Aged; Paresthesia; Pregabalin; Skin Ulcer; Syndrome; Trigeminal Nerve Diseases

Topics: Aged; Analgesics, Non-Narcotic; Carbamazepine; Dermatitis, Allergic Contact; Diagnosis, Differential; Drug Hypersensitivity Syndrome; Drug Interactions; Drug Therapy, Combination; Humans; Male; Patch Tests; Pregabalin; Syndrome; Trigeminal Neuralgia

Topics: Analgesics; Cicatrix; Facial Dermatoses; Humans; Male; Middle Aged; Pregabalin; Self-Injurious Behavior; Syndrome; Trigeminal Nerve Diseases

Red scrotum syndrome is a poorly understood, chronic dysesthetic erythema primarily involving the anterior scrotum. Previous reports have indicated that red scrotum syndrome is occasionally responsive to oral doxycycline and oral gabapentin. Otherwise, few therapies have proven successful in treating the disorder. We report two cases of red scrotum syndrome responding to oral pregabalin, an anticonvulsant medication commonly used for neuropathic pain. These two cases suggest pregabalin as an effective means for treating red scrotum syndrome and endorse a neuropathic etiology.

Topics: Erythema; Humans; Hyperalgesia; Male; Middle Aged; Pregabalin; Scrotum; Syndrome

A case of quadrilateral space syndrome is presented, where a large near-circumferential glenoid labrum tear led to a paralabral cyst that dissected into the quadrilateral space and caused a compressive neuropathy of the axillary nerve. This led to a 6-mo history of left shoulder pain, parasthesias, marked weakness to abduction, and marked denervation in both the deltoid and teres minor on electro-diagnostics. This is a presentation of interest as it is the only case report in the literature, to the authors' knowledge, where spontaneous resolution of entrapment occurred. This normally requires intervention for definitive management. It resolved through nonsurgical management with pregabalin, oxycodon, and naproxen medications, leading to good functional return, as well as pain and presumed muscle edema dissipation, while awaiting interventional consultation. It also illustrates that quadrilateral space syndrome is a difficult clinical diagnosis owing to the nonspecific symptom presentation, as well as weakness.

Topics: Aged; Analgesics, Opioid; gamma-Aminobutyric Acid; Humans; Male; Naproxen; Nerve Compression Syndromes; Oxycodone; Pregabalin; Remission, Spontaneous; Shoulder; Shoulder Pain; Syndrome; Treatment Outcome; Upper Extremity

Charles Bonnet syndrome is a condition characterised by the presence of visual hallucinations in patients having visual impairment most commonly reported in the seventh decade. We describe a case of a 55-year-old lady who had developed retinopathy causing significant visual loss secondary to diabetes mellitus. She had started seeing images of men for the past 2 months which made her feel uncomfortable and seek psychiatric help. She was aware that the hallucinations were not real but a part of her imagination. A detailed history did not reveal any psychopathology but the patient had several medical complications due to her uncontrolled diabetes. Pregabalin, which was started for her neuropathy, dramatically remitted her symptoms within 2 days.

Topics: Analgesics; Diabetic Neuropathies; Diabetic Retinopathy; Female; gamma-Aminobutyric Acid; Hallucinations; Humans; Middle Aged; Pregabalin; Syndrome; Vision Disorders