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To evaluate acute onset of anxiolytic activity using a dental anxiety model, 89 patients were randomised to double-blind single dose pregabalin 150 mg, alprazolam 0.5 mg or placebo 4 h before a scheduled dental procedure. A Dental Anxiety Total score >12 (moderate-to-severe) without meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth edition) (DSM-IV) anxiety disorder criteria was required. Efficacy and safety, assessed 2, 2.5, 3, 3.5 and 4 h postdose, included 100 mm Visual Analogue Scale for Anxiety (VAS-Anxiety; primary outcome), 100 mm VAS-Sedation and Time-to-Onset of Action Scale (TOAS), a patient-rated anti-anxiety drug-benefit scale (no [0] to full benefit [10]). Mixed model analysis found significantly greater VAS-A improvement slopes for pregabalin (t = -2.47; P = 0.014) and alprazolam (t = -2.39; P = 0.018). There was a significant improvement versus placebo in the TOAS from 2 h through endpoint in alprazolam patients and from 3 h onward in pregabalin patients. Pregabalin produced significantly greater increases in VAS-Sedation versus placebo from 2.5 h through 4 h (2 h onward for alprazolam). Notably, there was a higher correlation between TOAS and VAS-Sedation (r = +0.58) than VAS-Anxiety (r = -0.50) on Spearman's analysis. The majority of Adverse Effects (AEs) were mild, and the most frequent for pregabalin, alprazolam, and placebo, respectively, were fatigue (N = 7, 7, 3), dizziness (N = 6, 3, 3), attention disturbance (N = 3, 1, 0), somnolence (N = 3, 0, 0), feeling abnormal (N = 0, 2, 0) and balance disorder (N = 0, 2, 0). These results suggest that onset of clinically meaningful anxiolytic effect after single-dose pregabalin occurs within the first 3-4 h. Additional research is needed to determine whether anxiolytic effect occurs in generalized anxiety disorder populations by day 1 or within 3-4 h post-first dose.
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PMID:Early onset anxiolytic efficacy after a single dose of pregabalin: double-blind, placebo- and active-comparator controlled evaluation using a dental anxiety model. 1863 90

Fibromyalgia is a condition with widespread muscle pain. Prevalence studies showed that 2% to 7% of the population have fibromyalgia, which affects approximately one million Canadians. Fibromyalgia is most common in women, but it also involves men and children. As with most chronic illnesses, the causes of fibromyalgia are unknown. However, recent research supports underlying abnormalities in the central nervous system, which supports fibromyalgia as a chronic disease state and valid clinical entity. Pain is the primary symptom, often accompanied by overwhelming fatigue, sleep dysfunction and cognitive impairment. In 1990, the American College of Rheumatology developed diagnostic criteria for the diagnosis of fibromyalgia. Lifestyle changes, including pacing of activities and aerobic exercise, are very important in managing fibromyalgia symptoms. Emotional and behavioural therapy can also be helpful. Controlled trials of antidepressants, gabapentinoids, tramadol, zopiclone and sodium oxybate have shown effectiveness in fibromyalgia patients. Pregabalin and duloxetine were recently approved in the United States. Effective management of fibromyalgia is complex and requires a multidisciplinary treatment approach. Response and tolerance of different therapeutic interventions vary from patient to patient. Recent advances in the pathophysiology of fibromyalgia offer hope for new and improved therapies in the management of this disabling condition.
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PMID:Fibromyalgia: presentation and management with a focus on pharmacological treatment. 1922 4

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 alpha(2)delta-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.
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PMID:New treatment options in the management of fibromyalgia: role of pregabalin. 1933 59

Pregabalin is one of the latest antiepileptic drugs introduced for the treatment of partial epilepsy. Its efficacy and safety as adjunctive therapy in refractory partial epilepsy have been established in four double-blind placebo-controlled trials (n = 1396) and 4 long-term open-label studies (n = 1480). In 3 fixed-dose trials, the proportion of patients with a >/=50% reduction in seizure frequency across the effective dose-range (150-600 mg/day) ranged between 14% and 51%, with a clear dose-response relationship. Suppression of seizure activity could be demonstrated as early as day 2. The most frequently reported CNS-related adverse events included dizziness, somnolence, ataxia and fatigue, were usually mild or moderate, and tended to be dose related. In long-term studies, weight gain was reported as an adverse event by 24% of patients. When pregabalin dose was individualized to according to response within the 150 to 600 mg/day dose range, tolerability was considerably improved compared with use of a high-dose, fixed-dose regimen (600 mg/day) without titration. In long-term studies up to 4 years, no evidence of loss efficacy was identified. During the last year on pregabalin, 3.7% of patients were seizure-free. Pregabalin appears to be a useful addition to the therapeutic armamentariun for the management of refractory partial epilepsy.
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PMID:Pregabalin for the management of partial epilepsy. 1933 61

(1) Fibromyalgia is characterised by a range of symptoms that include muscle pain, fatigue and sleep disorders. Anxiety and depression are often also present. The cause is unknown. More women than men are affected; (2) The following review focuses on differential diagnoses and available treatments for fibromyalgia, based on a review of the literature using the standard Prescrire methodology; (3) Fibromyalgia is mainly diagnosed by excluding other possibilities. The principal differential diagnoses are rheumatic involvement of the spine, systemic inflammatory disorders, and hypothyroidism. Unlike these other conditions, fibromyalgia is not associated with radiological or laboratory abnormalities; (4) Paracetamol has not been compared with other treatments in fibromyalgia. Nonsteroidal antiinflammatory drugs have no specific effect; (5) The only two trials assessing tramadol showed little effect; in one study the average pain score was 53 mm in the tramadol group versus 65 mm in the placebo group, on a scale ranging from 0 to 100 mm. The adverse effects of tramadol are those of opiates in general, mainly nausea and dependence. Tramadol interacts with numerous other drugs; (6) The efficacy of tricyclic antidepressants is also difficult to quantify. Their limited superiority over placebo lasts no more than a few months. The efficacy of selective serotonin reuptake inhibitor antidepressants (fluoxetine, paroxetine and citalopram), serotonin and nonadrenaline reuptake inhibitors (duloxetine and milnacipran) is even less well established. Duloxetine has been tested in four placebo-controlled trials with unconvincing results; (7) Pregabalin and gabapentin, two antiepileptic drugs, appear to be more effective than placebo but have only been tested in short-term trials. In one trial 44% of patients in the pregabalin group said they felt better after 13 weeks versus 35% of patients in the placebo group. However, adverse effects are frequent and sometimes troublesome (drowsiness, dizziness, nausea, weight gain). In clinical trials, 19% to 33% of patients stopped treatment due to adverse effects after 13 weeks, depending on the dose of pregabalin; (8) Assessments of non-drug treatments in this setting are generally mediocre. The best-assessed alternative therapies (acupuncture and physical exercise) only have a limited effect; (9) In practice, when a patient presents with symptoms compatible with fibromyalgia, the first step is to rule out a treatable condition. Quality of life may be improved by first acknowledging that the pain is real, and possibly by providing psychological, medical, social and occupational support. The limited efficacy of available drugs, and their potential adverse effects, should be discussed with the patient.
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PMID:Fibromyalgia: poorly understood; treatments are disappointing. 1974 61

Pregabalin is effective in the treatment of peripheral and central neuropathic pain. This study evaluated the effectiveness of pregablin in management of post traumatic peripheral nerve injury facial pain not responding to other medication like analgesics. Pregabalin was well tolerated. The most common adverse effects were dizziness and tiredness.
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PMID:Pregabalin in post traumatic neuropathic pain: Case studies. 2325 Oct 69

Pregabalin, an approved treatment for fibromyalgia (FM), has been shown to decrease sympathetic nervous system (SNS) activity and inhibit sympathetically maintained pain, but its effects on exercise responses have not been reported. Methods. Using a randomized double-blind crossover design, we assessed the effect of 5 weeks of pregabalin (versus placebo) on acute cardiovascular and subjective responses to moderate exercise in 19 FM patients. Blood pressure (BP), heart rate (HR), and ratings of perceived exertion (RPE) during exercise and ratings of pain, physical fatigue, and mental fatigue before, during, and for 48 hours after exercise were compared in patients on pregabalin versus placebo and also versus 18 healthy controls. Results. On placebo, exercise RPE and BP were significantly higher in FM patients than controls (p < 0.04). Pregabalin responders (n = 12, defined by patient satisfaction and symptom changes) had significantly lower exercise BP, HR, and RPE on pregabalin versus placebo (p < 0.03) and no longer differed from controls (p > 0.26). Cardiovascular responses of nonresponders (n = 7) were not altered by pregabalin. In responders, pregabalin improved ratings of fatigue and pain (p < 0.04), but negative effects on pain and fatigue were seen in nonresponders. Conclusions. These preliminary findings suggest that pregabalin may normalize cardiovascular and subjective responses to exercise in many FM patients.
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PMID:Effect of Pregabalin on Cardiovascular Responses to Exercise and Postexercise Pain and Fatigue in Fibromyalgia: A Randomized, Double-Blind, Crossover Pilot Study. 2702 28