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Somnolence
Kinds of Somnolence Selected AbstractsAntiepileptic Drugs in Migraine PreventionHEADACHE, Issue 2001Ninan T. Mathew MD Migraineurs may continue to experience attacks, despite daily use of one or more agents from a wide range of drugs, including , -blockers, calcium channel blockers, serotonin antagonists, tricyclic antidepressants, monoamine oxidase inhibitors, and antiepileptic agents. Divalproex sodium is the only antiepileptic drug approved for migraine prevention. Gabapentin, topiramate, and other antiepileptic agents are being evaluated for migraine prevention and treatment. Prospective, double-blind, placebo-controlled clinical trials of divalproex, gabapentin, and topiramate for migraine prevention generally were composed of a prospective baseline period, a dose titration period, and a fixed-dose treatment period. The primary efficacy variable was a reduction in the 28-day frequency of migraine headache. Patients receiving divalproex for 12 weeks at doses up to 1500 mg/day achieved significant decreases in the migraine frequency (P<.05), corresponding to reductions of 30% to 40% compared with baseline. Nearly half of the divalproex-treated patients had a 50% or more reduction from baseline in headache frequencies (P.05). Asthenia, vomiting, somnolence, tremor, and alopecia were common adverse events associated with divalproex. Significant reductions in migraine frequency were also observed with gabapentin (1800 to 2400 mg/day) when compared with placebo (P<.01), and nearly half of all patients treated at the highest dose experienced a reduction in headache rate of 50% or more. Somnolence was the most commonly reported adverse event among the gabapentin-treated patients. Two single-center, double-blind, placebo-controlled clinical trials evaluated topiramate for migraine prevention. A lower 28-day migraine frequency was seen during 18 weeks of administration at a maximum daily dose of 200 mg (P = .09). In a second study, a significantly lower mean 28-day migraine frequency was observed during 16 weeks of treatment with topiramate (P = .0015). Mean reduction in migraine frequency was also significantly greater in topiramate-treated patients (P = .0037). Paresthesias, diarrhea, somnolence, and altered taste were commonly reported adverse events in the topiramate-treated patients. Unlike some patients given divalproex or gabapentin, some given topiramate reported weight loss. Large, double-blind, placebo-controlled trials may prove the effectiveness of novel antiepileptic drugs in migraine prevention. [source] The GABAB receptor agonist AZD9343 inhibits transient lower oesophageal sphincter relaxations and acid reflux in healthy volunteers: a phase I studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009H. BEAUMONT Summary Background, Transient lower oesophageal sphincter relaxations (TLESRs) represent an interesting target for the treatment of gastro-oesophageal reflux. Baclofen reduces TLESRs and reflux episodes, but is not optimal for clinical application because of its central side effects. Therefore, new agents are required. Aim, To study the effect of AZD9343, a new selective GABAB receptor agonist, in healthy volunteers. Methods, A total of 27 subjects participated in a placebo-controlled, randomized, two-centre phase I study. Subjects underwent oesophageal manometry and pH-metry for 3 h postprandially. Before meal ingestion, a single oral dose of placebo, 60 and 320 mg AZD9343 or 40 mg baclofen was given on four separate days. Results, Somnolence was reported after 320 mg AZD9343 and baclofen. Reversible short-lasting paraesthesia was reported after AZD9343. AZD9343 320 mg and baclofen significantly reduced the number of TLESRs with 32% and 40% respectively. Acid reflux was significantly decreased by AZD9343 and baclofen. Like baclofen, AZD9343 increased LES pressure before meal intake. AZD9343 320 mg and baclofen significantly reduced the swallowing rate. Conclusions, Like baclofen, AZD9343 dose-dependently decreases the number of TLESRs and acid reflux episodes, increases LES pressure and reduces swallowing, extending the concept that GABAB agonists are potent reflux inhibitors. However, discovery of analogues with an improved side effect profile is warranted. [source] Open-label pilot study of levetiracetam (Keppra) for the treatment of chorea in Huntington's diseaseMOVEMENT DISORDERS, Issue 11 2006FAAN, Theresa A. Zesiewicz MD Abstract The objective of this study is to evaluate the tolerability and preliminary efficacy of levetiracetam (LEV) in reducing chorea in Huntington's disease (HD) patients in a prospective open-label pilot study. Nine HD patients with chorea were treated with LEV in doses up to 3,000 mg/day for up to 48 days. The primary endpoint measure was the Unified Huntington's Disease Rating Scale (UHDRS) chorea subscore. The mean dose (±SD) of LEV at endpoint was 2,583.3 ± 1,020.6 mg/day. Mean UHDRS chorea score decreased from 12.6 ± 3.0 at baseline to 6.7 ± 4.3 at endpoint (P = 0.01). There was no significant change in UHDRS total motor scores (38.8 ± 11.4 at baseline and 33.6 ± 26.7 at endpoint; P = 0.24). Somnolence contributed to a 33% drop-out rate, and 3 patients developed Parkinsonism. Results of this open label study suggest that LEV may be efficacious in reducing chorea in HD patients. © 2006 Movement Disorder Society [source] Thalidomide for the Treatment of Refractory Multiple Myeloma: Association of Plasma Concentrations of Thalidomide and Angiogenic Growth Factors with Clinical OutcomeCANCER SCIENCE, Issue 9 2002Tsunayuki Kakimoto Recent reports showed that thalidomide has anti-angiogenic activity and is effective for the treatment of refractory multiple myeloma (MM). We examined the relationship between the clinical efficacy and adverse effects of thalidomide and the plasma concentrations of this drug as well as angiogenic growth factors in refractory MM. Ten out of twenty-four evaluable patients (42%) showed more than 25% reduction of M-protein, and eight (33%) achieved more than 50% reduction. These changes were associated with restoration of anemia and recovery of normal immunoglobulin level. Somnolence and headache, constipation, peripheral neuropathy and skin rash were frequently observed, but were well tolerated. However, grade 2,4 severe neutropenia was also observed in nine cases. These adverse effects other than neutropenia occurred more frequently in the patients with higher plasma concentrations of thalidomide (,2.0 ,g/ml at 12 h after the last administration) and were readily alleviated by dose reduction. In contrast, neutropenia developed regardless of the plasma concentration. Plasma concentrations of angiogenic growth factors were frequently elevated before treatment. After thalidomide treatment, these growth factor levels tend to decrease to near-normal ranges in responders but were still high in most non-responders. After thalidomide treatment, plasma vascular endothelial growth factor (VEGF) level was significantly reduced in responders (P=0.025), but not in non-responders (P=0.37). Reduction of plasma VEGF level might be an important indicator for anti-myeloma effect of thalidomide. [source] Risperidone in the treatment of disruptive behavioural symptoms in children with autistic and other pervasive developmental disordersCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 2 2005Richard ReadingArticle first published online: 16 FEB 200 Risperidone in the treatment of disruptive behavioural symptoms in children with autistic and other pervasive developmental disorders . SheaS, TurgayA, CarrollA, SchulzM, OrlikH, SmithI & DunbarF. ( 2004 ) Pediatrics , 114 , e634 , e641 . Objective To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioural symptoms in children with autism and other pervasive developmental disorders (PDD). Methods In this 8-week, randomized, double-blinded, placebo-controlled trial, risperidone/placebo solution (0.01,0.06 mg/kg/day) was administered to 79 children who were aged 5,12 years and had PDD. Behavioural symptoms were assessed using the Aberrant Behaviour Checklist (ABC), Nisonger Child Behaviour Rating Form and Clinical Global Impression-Change. Safety assessments included vital signs, electrocardiogram, extrapyramidal symptoms, adverse events and laboratory tests. Results Subjects who were taking risperidone (mean dosage: 0.04 mg/kg/day; 1.17 mg/day) experienced a significantly greater mean decrease on the irritability subscale of the ABC (primary endpoint) compared with those who were taking placebo. By study endpoint, risperidone-treated subjects exhibited a 64% improvement over baseline in the irritability score almost double that of placebo-treated subjects (31%). Risperidone-treated subjects also exhibited significantly greater decreases on the other four subscales of the ABC; on the conduct problem, insecure/anxious, hyperactive and overly sensitive subscales of the Nisonger Child Behaviour Rating Form (parent version); and on the Visual Analog Scale of the most troublesome symptom. More risperidone-treated subjects (87%) showed global improvement in their condition compared with the placebo group (40%). Somnolence, the most frequently reported adverse event, was noted in 72.5% vs. 7.7% of subjects (risperidone vs. placebo) and seemed manageable with dose/dose-schedule modification. Risperidone-treated subjects experienced statistically significantly greater increases in weight (2.7 vs. 1.0 kg), pulse rate and systolic blood pressure. Extrapyramidal symptoms scores were comparable between groups. Conclusions Risperidone was well-tolerated and efficacious in treating behavioural symptoms associated with PDD in children. [source] Thalidomide for the treatment of multiple myelomaCONGENITAL ANOMALIES, Issue 3 2004Yutaka Hattori ABSTRACT Although thalidomide was withdrawn in the 1960s after its teratogenic property was recognized, it was subsequently found that this drug possesses immunomodulatory and anti-inflammatory effects. Recent studies have also demonstrated that thalidomide has antineoplastic activity via an antiangiogenic mechanism. Observations in the late 1990s that the microenvironment in the bone marrow plays a role in tumor progression in multiple myeloma provided an impetus to use thalidomide for the treatment of this disease. It is known that thalidomide monotherapy is effective in one-third of refractory cases, and in combination with glucocorticoids and/or antineoplastic drugs, thalidomide provides a response rate of more than 50%. Thus, thalidomide therapy is considered a standard approach for the treatment of relapsed and refractory myeloma. The exact mechanism of the antimyeloma effect of thalidomide is not yet clearly understood. Anti-angiogenic effects, direct activity in tumor cells such as the induction of apoptosis or G1 arrest of the cell cycle, the inhibition of growth factor production, the regulation of interactions between tumor and stromal cells, and the modulation of tumor immunity have been considered as possible mechanisms. In addition to its teratogenicity, the adverse effects of thalidomide have been general symptoms such as somnolence and headache, peripheral neuropathy, constipation, skin rash, and other symptoms. Although these adverse effects are generally reversible and mild, grade 3 and 4 toxicities such as peripheral neuropathy, deep venous thrombosis, neutropenia, and toxic dermal necrosis have occasionally been reported. The application of thalidomide therapy in patients with multiple myeloma is being broadened to include not only cases of refractory myeloma, but also previously untreated cases, as well as for maintenance therapy after hematopoietic stem cell transplantation and for the treatment of other hematological diseases. The safe use of this drug will depend on the establishment of diagnostic and treatment guidelines. In addition, the establishment of a nation-wide regulation system is urgently needed in Japan. [source] Efficacy and safety of duloxetine in the treatment of generalized anxiety disorder: a flexible-dose, progressive-titration, placebo-controlled trialDEPRESSION AND ANXIETY, Issue 3 2008Moira Rynn M.D. Abstract Generalized anxiety disorder (GAD), a prevalent and chronic illness, is associated with dysregulation in both serotonergic and noradrenergic neurotransmission. Our study examined the efficacy, safety, and tolerability of duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, for short-term treatment of adults with GAD. In a 10-week, double-blind, progressive-titration, flexible-dose trial, 327 adult outpatients with a DSM-IV,defined GAD diagnosis were randomized to duloxetine 60,120,mg (DLX, N=168) or placebo (PLA, N=159) treatment. The primary efficacy measure was mean change from baseline to endpoint in Hamilton Anxiety Scale (HAMA) total score. Secondary outcome measures included response rate (HAMA total score reduction ,50% from baseline), Clinician Global Impression,Improvement (CGI-I) scores, and Sheehan Disability Scale (SDS) scores. Patients who received duloxetine treatment demonstrated significantly greater improvement in HAMA total scores (P=.02); a higher response rate (P=.03), and greater improvement (P=.04) than patients who received placebo. Duloxetine-treated patients were also significantly more improved than placebo-treated patients on SDS global functional (P<.01) and work, social, and family/home impairment scores (P<.05). The rate of discontinuation due to adverse events (AEs) was higher for the duloxetine group compared with the placebo group (P=.002). The AEs most frequently associated with duloxetine were nausea, dizziness, and somnolence. Duloxetine was an efficacious, safe, and well-tolerated treatment that resulted in clinically significant improvements in symptom severity and functioning for patients with GAD. Depression and Anxiety 0:1,8, 2007. © 2007 Wiley-Liss, Inc. [source] Intravenous lacosamide as short-term replacement for oral lacosamide in partial-onset seizuresEPILEPSIA, Issue 6 2010Gregory Krauss Summary Purpose:, Lacosamide is a new antiepileptic drug effective for adjunctive treatment of partial-onset seizures. We evaluated the safety and tolerability of an intravenous (i.v.) formulation of lacosamide (200,800 mg/day) infused over 10, 15, and 30 min as short-term replacement for oral lacosamide in patients with partial-onset seizures. Methods:, This multicenter, open-label, inpatient trial enrolled 160 patients from ongoing open-label, long-term trials who were taking stable doses of oral lacosamide and up to three concomitant antiepileptic drugs (AEDs). Serial cohorts of patients were converted from oral lacosamide treatment to the same intravenous doses infused over progressively shorter infusion durations: 30, 15, and 10 min for 2,5 days. A data monitoring committee (DMC) reviewed safety data for each cohort. The safety of intravenous lacosamide was assessed from adverse events (AEs), laboratory variables, electrocardiography findings, and physical/neurologic examinations. Results:, A total of 160 patients received lacosamide 200,800 mg/day, i.v., for 2,5 days, of which 69% received 400,800 mg/day doses. The most common AEs (reported by ,10% of patients) were headache, dizziness, and somnolence. There was no increase in frequency or severity of AEs with shorter durations of infusion or increased days of exposure. AEs were similar, but more frequent, with higher doses (,400 mg/day). Injection-site events were rare and did not appear to be linked to infusion doses or rates. Lacosamide plasma concentrations were linearly related to dose across the cohorts. Discussion:, This comprehensive evaluation supports the safety of an intravenous lacosamide infusion duration as short as 15 min for short-term (2,5 days) replacement for patients temporarily unable to take oral lacosamide. [source] Carisbamate as adjunctive treatment of partial onset seizures in adults in two randomized, placebo-controlled trialsEPILEPSIA, Issue 3 2010Michael R. Sperling Summary Purpose:, To assess the efficacy, safety, and tolerability of the investigational drug carisbamate as adjunctive treatment for partial-onset seizures (POS). Methods:, Two identical, randomized, placebo-controlled, double-blind studies were conducted in adults with POS uncontrolled for ,1 year. Therapy-refractory epilepsy patients (,16 years) remained on stable doses of prescribed antiepileptic drugs (,2) for an 8-week prospective baseline phase and were then randomized (1:1:1) to carisbamate 200 mg/day, carisbamate 400 mg/day, or placebo, for a 12-week double-blind phase. Primary efficacy end points were percent reduction in seizure frequency and responder rate (patients with ,50% reduction in POS frequency) during the double-blind phase compared with the prospective baseline phase. Results:, Of the 565 patients randomized in study 1, 93% completed the study; of the 562 randomized in study 2, 94% completed the study. Patient characteristics were similar across both studies and treatment arms: mean age, 35 years (study 1, range 16,75 years) and 36 years (study 2, range 16,74 years); approximately 50% were men. Treatment with carisbamate 400 mg/day resulted in significant improvement (p < 0.01) in both efficacy measures compared with placebo in study 1 but not in study 2. Carisbamate 200 mg/day did not differ statistically from placebo in either study. Among the most common treatment-emergent adverse events (,5% in any group), those with an incidence exceeding placebo (,3%) were dizziness (400 mg/day group) and somnolence. Conclusions:, Carisbamate 400 mg/day was effective in patients with refractory partial-onset seizures in one of these global studies. More than 200 mg/day of carisbamate is required for efficacy. Carisbamate was well-tolerated in both studies. [source] Time Course of Adverse Events in Patients with Localization-related Epilepsy Receiving Topiramate Added to CarbamazepineEPILEPSIA, Issue 5 2005Jerzy Majkowski Summary:,Purpose: To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy. Methods: Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (,5% incidence) AEs were calculated for patients completing the 12-week study. Results: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits. Conclusions: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy. [source] Efficacy and Safety of Levetiracetam in Children with Partial Seizures: An Open-label TrialEPILEPSIA, Issue 5 2002Tracy A. Glauser Summary: ,Purpose: To assess the efficacy and safety of levetiracetam (LEV) as adjunctive therapy in children with treatment-resistant partial-onset seizures. Methods: Children (aged 6,12 years) with treatment-resistant partial-onset seizures receiving one standard antiepileptic drug (AED) were eligible. After a 4-week baseline period, children received LEV in a 6-week titration phase (target dose, 40 mg/kg/day) followed by an 8-week evaluation phase. Seizure frequency during the evaluation period with individualized LEV doses (20,40 mg/kg/day) were compared with the 4-week baseline seizure frequency. Plasma concentrations of LEV and other AEDs were determined to evaluate potential drug interactions. Results: Twenty-four subjects enrolled and received LEV; 23 entered the evaluation phase, and 22 completed the evaluation phase. Compared with their baseline seizure frequency, 12 (52%) of 23 subjects entering the evaluation phase had their seizure frequency decrease by >50%. Two subjects remained seizure free during the entire evaluation period. LEV did not significantly affect plasma concentrations of any concomitant AED during this study, and no alteration of mean clinical laboratory values was observed. The most commonly reported adverse events were headache, infection, anorexia, and somnolence. Conclusions: This open-label study of adjunctive LEV therapy (at 20,40 mg/kg/day) suggests that LEV is effective, safe, and well tolerated in children ages 6,12 years with treatment-resistant partial-onset seizures. A randomized, placebo-controlled, double-blind trial of LEV adjunctive therapy in children with treatment-resistant partial-onset seizures is needed and ongoing to confirm these open-label findings. [source] A systematic review of phase II trials of thalidomide/dexamethasone combination therapy in patients with relapsed or refractory multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2008Marie Von Lilienfeld-Toal Abstract Thalidomide monotherapy in relapsed/refractory multiple myeloma (MM) has a response rate of 30%. The combination of thalidomide with dexamethasone (Thal/Dex) is expected to improve responses, but it is unknown if the combination increases the rate of adverse events. Here, we conducted a systematic review of studies evaluating Thal/Dex in relapsed/refractory MM. Twelve studies were included, comprising 451 patients. The response rate (CR and PR) was 46% (95% CI 42,51%). Therapy-related toxicity was comparable to thalidomide monotherapy and included somnolence (26%, 95% CI 22,31%), constipation (37%, 95% CI 32,42%) and peripheral neuropathy (27%, 95% CI 23,32%). Only venous thromboembolism appeared to occur more often with Thal/Dex (5%, 95% CI 3,8%). Thus, using Thal/Dex results in an improved response rate in relapsed/refractory MM, with a toxicity rate comparable to thalidomide monotherapy. [source] Sleep disruption, daytime somnolence and ,sleep attacks' in Parkinson's disease: a clinical survey in PD patients and age-matched healthy volunteersEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2006J. J. Ferreira Recent case reports of ,sleep attacks' (SA) in patients with Parkinson's disease (PD) generated concerns about drug-induced daytime somnolence in this population. However, there are nearly no comparative data on sleep and vigilance problems between PD patients and normal controls. We performed a cross-sectional survey in PD patients and age-matched controls using a structured questionnaire on PD history, treatments, co-morbidity, activities of daily living, habits, exercise, sleep pattern, driving, pre-existing nocturnal problems, daytime somnolence, episodes of SA and the circumstances in which such episodes occurred. Daytime somnolence was also measured with the Epworth Sleepiness Scale (ESS) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). 176 PD patients and 174 controls were included. The same proportion of PD patients (27%) and controls (32%) reported episodes of SA, but these were more frequent in PD patients and occurred more frequently during situations requiring attention (10.8% vs. 1.7%, p<10,3). More PD patients had abnormal daytime somnolence (ESS) and poor sleeping quality (PSQI). The most consistent factor associated with SA was the duration of levodopa therapy and the predictive value of an abnormal ESS score was rather poor (40.7%). Abnormal daytime somnolence and poor sleep quality at night are more frequent in PD patients than in normals. However, SA are reported in both groups, although less frequently in the normals during activities that requires attention. [source] Long-Term, Open-Label Safety Study of Oral Almotriptan 12.5 mg for the Acute Treatment of Migraine in AdolescentsHEADACHE, Issue 5 2010Frank Berenson MD (Headache 2010;50:795-807) Objectives., This study evaluated the long-term safety of oral almotriptan 12.5 mg for the treatment of multiple migraine episodes in adolescents over a 12-month period. Efficacy outcomes were assessed as a secondary objective. Methods., Adolescent migraineurs aged 12-17 years were enrolled in this 12-month, open-label study (Study ID CR002827). Patients were instructed to record their assessments on paper headache records whenever they experienced a migraine headache that they treated with study medication. Safety was assessed descriptively and assessments included adverse event (AE) recording, change in laboratory values, vital signs, and electrocardiogram parameters. Efficacy outcomes were assessed descriptively and outcomes included rates for 2- and 24-hour pain relief and sustained pain relief, 2- and 24-hour pain-free and sustained pain-free, and presence of migraine-associated symptoms of photophobia, phonophobia, nausea and vomiting. Results., Overall, 67.1% of patients reported ,1 AE over the course of the trial, 7.6% had an AE judged by the study investigator to be related to treatment with almotriptan, 2.4% discontinued because of an AE, and 1.9% reported serious AEs. The most commonly reported treatment-related AEs (occurring in ,1% of patients) were nausea (1.4%) and somnolence (1.4%). Pain relief responses for treated migraines of moderate or severe intensity at baseline were 61.7% and 68.6%, at 2 and 24 hours, respectively; the sustained pain relief rate was 55.5%. Pain-free responses were reported for 40.5% of all treated migraines at 2 hours and 65.9% of treated migraines at 24 hours; the sustained pain-free rate was 38.4%. The proportion of migraines that achieved the pain relief, sustained pain relief, pain-free and sustained pain-free endpoints were similar in the 12- to 14-year and 15- to 17-year age groups. Treating with almotriptan 12.5 mg when headache pain was mild was associated with higher rates of pain relief and pain-free at 2 and 24 hours, and sustained pain relief and sustained pain-free, compared with treatment initiated when pain was severe. Conclusions., Almotriptan 12.5 mg was well tolerated in this adolescent population over a 12-month period. No unexpected safety or tolerability concerns were revealed over the course of this study. The results are consistent with almotriptan 12.5 mg being effective for the acute treatment of pain and symptoms associated with migraine in both younger and older adolescents. [source] Meta-Analysis Examining the Efficacy and Safety of Almotriptan in the Acute Treatment of MigraineHEADACHE, Issue 8 2007Li-Chia Chen PhD Objective.,To evaluate the comparative efficacy and safety of oral almotriptan in treating acute migraine attacks. Background.,Almotriptan is an oral selective sertonin1B/1D receptor agonist (triptan) with a high bioavailability and short half-life, developed for the treatment of migraine. In recent years, a number of randomized controlled trials have been published examining the efficacy and safety of almotriptan in the acute treatment of migraine. Methods.,Systematic review and meta-analysis of randomized controlled trials (RCTs) using a random-effects model to estimate the pooled rate ratios (RRs) and 95% confidence intervals (95%CI) for the proportions of patients achieving headache relief and pain-free responses at 1 or 2 hours post-dose, sustained pain-free response at 2,24 hours post-dose, and safety outcomes (proportions of patients experiencing any adverse events, dizziness, somnolence, asthenia, and chest tightness) comparing almotriptan against placebo, other triptans, and different dosages of almotriptan. Absolute rate differences (ARDs) for 2-hour headache relief, pain free, and sustained pain free responses between almotriptan and placebo were also calculated. Results.,Eight RCTs involving 4995 patients were included in the analysis. Almotriptan 12.5 mg was significantly more effective than placebo for all efficacy outcomes (RRs ranged from 1.47 to 2.15; ARDs ranged from 0.01 to 0.28) and there were no significant differences in any of the safety outcomes. There were also no significant differences in efficacy outcomes comparing almotriptan 12.5 mg against sumatriptan 100 mg and zolmitriptan 2.5 mg, but almotriptan 12.5 mg was associated with significantly fewer adverse events than sumatriptan 100 mg (RR: 0.39, 95%CI: 0.23, 0.67). However, there was no significant difference between almotriptan and sumatriptan in terms of clinically important adverse effects, such as dizziness, somnolence, asthenia, and chest tightness. Almotriptan 12.5 mg was significantly less effective than almotriptan 25 mg for 1-hour pain-free response (RR: 0.45, 95%CI: 0.21, 0.95), but associated with significantly fewer patients experiencing adverse events (RR: 0.61, 95%CI: 0.41, 0.91) than almotriptan 25 mg. Conclusions.,Almotriptan 12.5 mg is an effective treatment for acute attacks of migraine, in particular, it has been found to be as effective as sumatriptan 100 mg and zolmitriptan 2.5 mg. The risk of adverse events associated with almotriptan 12.5 mg was similar to placebo and significantly lower than sumatriptan 100 mg. Further research is required to assess the comparative efficacy of almotriptan against other triptans. [source] Antiepileptic Drugs in Migraine PreventionHEADACHE, Issue 2001Ninan T. Mathew MD Migraineurs may continue to experience attacks, despite daily use of one or more agents from a wide range of drugs, including , -blockers, calcium channel blockers, serotonin antagonists, tricyclic antidepressants, monoamine oxidase inhibitors, and antiepileptic agents. Divalproex sodium is the only antiepileptic drug approved for migraine prevention. Gabapentin, topiramate, and other antiepileptic agents are being evaluated for migraine prevention and treatment. Prospective, double-blind, placebo-controlled clinical trials of divalproex, gabapentin, and topiramate for migraine prevention generally were composed of a prospective baseline period, a dose titration period, and a fixed-dose treatment period. The primary efficacy variable was a reduction in the 28-day frequency of migraine headache. Patients receiving divalproex for 12 weeks at doses up to 1500 mg/day achieved significant decreases in the migraine frequency (P<.05), corresponding to reductions of 30% to 40% compared with baseline. Nearly half of the divalproex-treated patients had a 50% or more reduction from baseline in headache frequencies (P.05). Asthenia, vomiting, somnolence, tremor, and alopecia were common adverse events associated with divalproex. Significant reductions in migraine frequency were also observed with gabapentin (1800 to 2400 mg/day) when compared with placebo (P<.01), and nearly half of all patients treated at the highest dose experienced a reduction in headache rate of 50% or more. Somnolence was the most commonly reported adverse event among the gabapentin-treated patients. Two single-center, double-blind, placebo-controlled clinical trials evaluated topiramate for migraine prevention. A lower 28-day migraine frequency was seen during 18 weeks of administration at a maximum daily dose of 200 mg (P = .09). In a second study, a significantly lower mean 28-day migraine frequency was observed during 16 weeks of treatment with topiramate (P = .0015). Mean reduction in migraine frequency was also significantly greater in topiramate-treated patients (P = .0037). Paresthesias, diarrhea, somnolence, and altered taste were commonly reported adverse events in the topiramate-treated patients. Unlike some patients given divalproex or gabapentin, some given topiramate reported weight loss. Large, double-blind, placebo-controlled trials may prove the effectiveness of novel antiepileptic drugs in migraine prevention. [source] Antiepileptic Drugs in the Management of Cluster Headache and Trigeminal NeuralgiaHEADACHE, Issue 2001Todd D. Rozen MD Cluster headache and trigeminal neuralgia are relatively rare but debilitating neurologic conditions. Although they are clinically and diagnostically distinct from migraine, many of the same pharmacologic agents are used in their management. For many patients, the attacks are so frequent and severe that abortive therapy is often ineffective; therefore, chronic preventive therapy is necessary for adequate pain control. Cluster headache and trigeminal neuralgia have several distinguishing clinical features. Cluster headache is predominantly a male disorder; trigeminal neuralgia is more prevalent in women. Individuals with cluster headaches often develop their first attack before age 25; most patients with trigeminal neuralgia are between age 50 and 70. Cluster headaches are strongly associated with tobacco smoking and triggered by alcohol consumption; trigeminal neuralgia can be triggered by such stimuli as shaving and toothbrushing. Although the pain in both disorders is excruciating, cluster headache pain is episodic and unilateral, typically surrounds the eye, and lasts 15 to 180 minutes; the pain of trigeminal neuralgia lasts just seconds and is usually limited to the tissues overlying the maxillary and mandibular divisions of the trigeminal nerve. Cluster headache is unique because of its associated autonomic symptoms. Although the pathophysiology of cluster headache and trigeminal neuralgia are not completely understood, both appear to have central primary processes, and these findings have prompted investigations of the effectiveness of the newer antiepileptic drugs for cluster headache prevention and for the treatment of trigeminal neuralgia. The traditional antiepileptic drugs phenytoin and carbamazepine have been used for the treatment of trigeminal neuralgia for a number of years, and while they are effective, they can sometimes cause central nervous system effects such as drowsiness, ataxia, somnolence, and diplopia. Reports of studies in small numbers of patients or individual case studies indicate that the newer antiepileptic drugs are effective in providing pain relief for trigeminal neuralgia and cluster headache sufferers, with fewer central nervous system side effects. Divalproex has been shown to provide effective pain control and to reduce cluster headache frequency by more than half in episodic and chronic cluster headache sufferers. Topiramate demonstrated efficacy in a study of 15 patients, with a mean time to induction of cluster headache remission of 1.4 weeks (range, 1 day to 3 weeks). In the treatment of trigeminal neuralgia, gabapentin has been shown to be effective in an open-label study. When added to an existing but ineffective regimen of carbamazepine or phenytoin, lamotrigine provided improved pain relief; it also may work as monotherapy. Topiramate provided a sustained analgesic effect when administered to patients with trigeminal neuralgia. The newer antiepileptic drugs show considerable promise in the management of cluster headache and trigeminal neuralgia. [source] Fatigue in primary biliary cirrhosis is associated with excessive daytime somnolence,HEPATOLOGY, Issue 1 2006Julia L. Newton A significant proportion of patients with primary biliary cirrhosis (PBC) suffer from severe fatigue. The aim of this study was to characterize patterns of daytime sleep in patients with PBC (using both objective and subjective assessment approaches) and to study the association between sleep abnormality and fatigue severity. Fatigue severity was assessed in 48 female subjects with PBC (using a disease-specific quality of life instrument (the PBC-40) and a generic fatigue measure (Fatigue Impact Scale [FIS]) as well as 48 case-matched normal controls. All participants also completed the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS, which assesses daytime hypersomnolence). Objective sleep assessment was performed using accelerometry over 7 days. Global sleep quality assessed by the PSQI was significantly lower in the PBC group compared to controls (P < .0001). ESS scores were significantly higher in patients with PBC than controls (P = .0001), suggesting significantly greater daytime somnolence in the patients with PBC. Objective sleep assessment confirmed that subjects with PBC were sleeping on average almost twice as long as controls during the daytime. Both degree of daytime somnolence (ESS) and actual daytime sleep activity (accelerometry) correlated strongly with fatigue severity in the patient group (r2 = 0.5, P < .0001 and r2 = 0.2, P < .01, respectively). In conclusion, Sleep abnormality, in the form of excessive daytime somnolence, is present in a significant proportion of patients with PBC, with the degree of daytime somnolence correlating strongly with the degree of fatigue. Existing agents effective at reducing daytime somnolence (such as modafinil) hold potential for the treatment of fatigue in PBC. (HEPATOLOGY 2006;44:91,98.) [source] Safety and tolerability of duloxetine in the treatment of major depressive disorder: analysis of pooled data from eight placebo-controlled clinical trialsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2005James I. Hudson Abstract Objective To examine the safety and tolerability of the antidepressant duloxetine across multiple studies for major depressive disorder (MDD). Method Safety data were integrated from the acute phases of eight double-blind, placebo-controlled trials in which patients were randomized to duloxetine (40,120,mg/d; n,=,1139) or placebo (n,=,777) for up to 9 weeks. This data set included all acute-phase clinical trials that formed the basis of the New Drug Application (United States) or European Union submission package for duloxetine in the treatment of MDD. Two studies included continuation phases in which acute treatment responders received duloxetine or placebo for an additional 26 weeks. Safety assessments included serious adverse event reports, rates of discontinuation, spontaneously reported treatment-emergent adverse events, changes in vital signs and laboratory values, and electrocardiograms. Results The rates of serious adverse events for duloxetine- and placebo-treated patients were 0.3% and 0.6%, respectively (p,=,0.282). Adverse events led to discontinuation in 9.7% of duloxetine-treated patients, compared with 4.2% of patients receiving placebo (p,<,0.001). Treatment-emergent adverse events with an incidence for duloxetine ,,5.0% and significantly greater than placebo were nausea, dry mouth, constipation, insomnia, dizziness, fatigue, somnolence, increased sweating and decreased appetite. Mean changes in blood pressure and heart rate were small, and the incidence of increases above normal ranges was low. Duloxetine-treated patients had a mean decrease in weight of 0.5,kg compared with an increase of 0.2,kg for patients receiving placebo (p,<,0.001). No significant differences were found between duloxetine and placebo in the incidence of potentially clinically significant laboratory values at anytime while on treatment. Conclusion These results are consistent with those obtained previously from smaller pooled data sets, and suggest that duloxetine is safe and well tolerated in patients with MDD. Copyright © 2005 John Wiley & Sons, Ltd. [source] Mirtazapine and paroxetine: a drug-drug interaction study in healthy subjectsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2001F. J. L. Ruwe Abstract Paroxetine inhibits cytochrome P450 2D6, which is involved in the metabolism of mirtazapine. The possible drug-drug interaction between two pharmacologically distinct antidepressants, mirtazapine and paroxetine, has been investigated in a randomized, three-way crossover study in 24 healthy male and female subjects. After a titration phase of 3 days, each subject received single daily doses of 30,mg mirtazapine, 40,mg paroxetine or the combination for 6 days. Assessments included serial blood sampling for pharmacokinetics at steady state, cognitive testing using the test battery of CDR Ltd, a visual analogue mood rating scale (Bond and Lader) and the Leeds Sleep Evaluation Questionnaire. Paroxetine inhibits the metabolism of mirtazapine, as shown by increases of approximately 17% and 25% of the 24,h AUC's of mirtazapine and its demethyl metabolite, respectively. Mirtazapine did not alter the pharmacokinetics of paroxetine. The combined administration of mirtazapine and paroxetine probably does not alter cognitive functioning or result in major changes on the visual analogue mood rating scale and Sleep Evaluation Questionnaire, compared with the administration of either drug alone. The incidence of adverse events was lower during combined administration of mirtazapine and paroxetine than during administration of either drug alone. Fatigue, dizziness, headache, nausea, anxiety and somnolence were the most common adverse events during combined administration. These data suggest that the combination of mirtazapine and paroxetine is unlikely to lead to clinically relevant drug-drug interactions and can be used without dose adjustment of either drug. The combination may even be better tolerated than either drug alone. Copyright © 2001 John Wiley & Sons, Ltd. [source] Iloperidone for schizophrenia: a review of the efficacy and safety profile for this newly commercialised second-generation antipsychoticINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2009L. Citrome Summary Objective:, The aim of the study was to describe the efficacy and safety of iloperidone for the treatment of schizophrenia. Data sources:, The pivotal registration trials were accessed by querying http://www.pubmed.gov, http://www.fda.gov and http://www.clinicaltrials.gov for the search term ,iloperidone'. Study selection:, Four published primary reports of phase III studies were identified as well as preclinical animal and receptor affinity studies that describe potential mechanisms of action and pharmacogenomic studies that identify potential genetic biomarkers for efficacy and tolerability. Product labelling provided additional data. Data extraction:, Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Data synthesis:, Iloperidone is a second-generation antipsychotic agent indicated for the acute treatment of schizophrenia in adults. Iloperidone has been evaluated in several double-blind placebo-controlled clinical trials. The oral formulation has demonstrated efficacy in reducing the symptoms of acute schizophrenia at fixed daily doses ranging from 12 to 24 mg. Data reported for categorical definitions of response using the Positive and Negative Syndrome Scale were limited to one study and specifically to rates of achieving a , 20% decrease in the positive subscale from baseline; significantly more patients receiving iloperidone 24 mg/day (72%) than placebo (52%) met this criterion, yielding a NNT of five. Iloperidone should be titrated slowly to avoid orthostatic hypotension, potentially delaying the achievement of a therapeutic dose level. There appears to be a dose relationship for adverse events such as dizziness, somnolence and dry mouth; for example NNH vs. placebo for somnolence was 25 for iloperidone 10,16 mg/day and 10 for 20,24 mg/day. There is a possibility of a therapeutic dose response as well. Iloperidone is essentially free of extra-pyramidal side effects. Iloperidone is associated with weight gain comparable with risperidone. Long-term double-blind maintenance studies have demonstrated iloperidone's non-inferiority to haloperidol for relapse prevention. Product labelling includes a warning about the potential for QT interval prolongation. At present there are no efficacy studies available that are powered to directly compare iloperidone with other second-generation antipsychotics. The development of a depot formulation of iloperidone as well as efforts to identify genetic biomarkers for prediction of both efficacy and tolerability are in progress. Conclusions:, Aside from paliperidone, iloperidone is the first new second-generation antipsychotic to be commercialised in the USA since 2002. From the limited registration data, iloperidone appears to be relatively well tolerated once titrated to a therapeutic level and can be a useful option to consider. The development of a depot formulation and potential for genetic biomarkers may make this agent compelling. Further comparisons with other available agents among patients with schizophrenia in the ,real world' are needed. [source] Pregabalin for peripheral neuropathic pain: results of a multicenter, non-comparative, open-label study in Indian patientsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2006LYRICA STUDY GROUP Summary The aim of this study was to evaluate the tolerability, safety and efficacy of pregabalin in Indian patients with peripheral neuropathic pain. In this prospective, multicenter, non-comparative, open-label study, patients with peripheral neuropathic pain (n = 111) received pregabalin in doses ranging from 75 to 300 mg twice daily for 3 weeks. Primary efficacy measures included weekly pain score and the Visual Analogue Scale (VAS) score of the Short-Form McGill Pain Questionnaire (SF-MPQ). Despite a short study duration, a significant reduction was seen in weekly pain score (p < 0.0001), as well as VAS score of SF-MPQ (p < 0.0001). Significant improvements were also seen in other pain-related endpoints, weekly sleep interference score, quality of life measures, and patient and clinician ratings of global improvement. Pregabalin was well tolerated, and the most common adverse events were dizziness and somnolence. The short study duration precluded the assessment of longer term safety issues such as weight gain. This study has demonstrated the safety, tolerability and efficacy of pregabalin for peripheral neuropathic pain in Indian patients. [source] Subjectively reported sleep quality and excessive daytime somnolence in Parkinson's disease with and without dementia, dementia with Lewy bodies and Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 6 2007Frauke Boddy Abstract Objective We compared subjective sleep quality and excessive daytime somnolence (EDS) in controls, Parkinson's disease with (PDD) and without dementia (PD), dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). We investigated whether sleep dysfunction and EDS associate with motor phenotype in PD, PDD and DLB. Method Assessments included the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Results EDS was more frequent in PD, DLB and PDD patients than in AD. PDD, PD and DLB patients also had worse sleep quality when compared with AD and controls. Baseline postural instability-gait difficulty (PIGD) motor phenotype in PDD was associated with a higher ESS score and frequency of EDS, but this association was lost at two years. PSQI scores did not differ between PIGD dominant and non-dominant PD, PDD and DLB patients. Conclusion EDS and poor sleep quality are greater in PD, PDD and DLB, compared with AD. The dissociation of EDS and motor phenotype suggests their pathophysiology is anatomically and/or temporally distinct. Copyright © 2006 John Wiley & Sons, Ltd. [source] Lenalidomide in the treatment of multiple myeloma: a reviewJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2008X. Armoiry PharmD PhD Summary Lenalidomide is an immunomodulatory drug derived from thalidomide. It was developed to maximize the anti-inflammatory and anti-neoplasic properties of thalidomide and to reduce its toxicity. The molecular mechanism of action of lenalidomide is unclear, but its therapeutic activity is mainly due to its well defined anti-inflammatory, immunomodulatory, anti-proliferative and anti-angiogenic properties. In relapsed or refractory multiple myeloma (MM), lenalidomide, combined with standard dose dexamethasone, is superior to dexamethasone alone in terms of time to progression, response rate and overall survival. The most commonly reported adverse events include haematological toxicity with manageable neutropenia and thrombopenia. Lenalidomide does not trigger the limiting toxicities of thalidomide: somnolence, neuropathy and constipation. Lenalidomide, in combination with dexamethasone, is indicated for the treatment of MM patients who have received at least one prior therapy and is administered orally at the dose of 25 mg q.d. for 21 days of 28-day cycles. The drug is being investigated for the treatment of newly diagnosed MM. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical trial data on lenalidomide. [source] Sleep problems and daytime somnolence in a German population-based sample of snoring school-aged childrenJOURNAL OF SLEEP RESEARCH, Issue 1 2007STEFFEN EITNER Summary Habitual snoring is associated with daytime symptoms like tiredness and behavioral problems. Its association with sleep problems is unclear. We aimed to assess associations between habitual snoring and sleep problems in primary school children. The design was a population-based cross-sectional study with a nested cohort study. The setting was twenty-seven primary schools in the city of Hannover, Germany. Habitual snoring and sleep problems were assessed in primary school children using an extended version of Gozal's sleep-disordered breathing questionnaire (n = 1144). Approximately 1 year later, parents of children reported to snore habitually (n = 114) and an equal number of children who snored never or occasionally were given the Sleep Disturbance Scale for Children, a validated questionnaire for the assessment of pediatric sleep problems. Snoring status was re-assessed using the initial questionnaire and children were then classified as long-term habitual snorers or ex-habitual snorers. An increasing prevalence of sleep problems was found with increasing snoring frequency for sleep-onset delay, night awakenings, and nightmares. Long-term habitual snorers were at significantly increased risk for sleep,wake transition disorders (e.g. rhythmic movements, hypnic jerks, sleeptalking, bruxism; odds ratio, 95% confidence interval: 12.0, 3.8,37.3), sleep hyperhidrosis (3.6, 1.2,10.8), disorders of arousal/nightmares (e.g. sleepwalking, sleep terrors, nightmares; 4.6, 1.3,15.6), and excessive somnolence (i.e. difficulty waking up, morning tiredness, daytime somnolence; 6.3, 2.2,17.8). Ex-habitual snorers were at increased risk for sleep,wake transition disorders (4.4, 1.4,14.2). Habitual snoring was associated with several sleep problems in our study. Long-term habitual snorers were more likely to have sleep problems than children who had stopped snoring spontaneously. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 62JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003C Briani Thalidomide seems to be effective in the treatment of cutaneous forms of lupus erythematosus refractory to other therapies. Peripheral neuropathy is the most severe side effect, but the incidence of neuropathy and its relation to thalidomide doses are still unclear. We prospectively monitored 12 patients treated with thalidomide for cutaneous lupus erythematosus in order to estimate the occurrence of side effects, particularly peripheral neuropathy. A total of 12 female patients, median age 38,6 years (range 26,56), with subacute or chronic cutaneous lupus erythematosus were considered. The patients were treated with low dose thalidomide (starting dose 100 mg, tapered to 50 mg/day or 50 mg alternative day) for up to 18 months. The average follow-up period was 8,6 months (range 2,18). Prior to, and regularly during treatment patients underwent neurological evaluation and electrophysiological study of at least 8 nerves in the 4 arms (ulnar, median, sural, peroneal nerves). At recruitment, one patient presented a sensory-motor peripheral neuropathy. Of the remaining 11 patients, six did not present electrophysiological evidence of neuropathy, one had a carpal tunnel syndrome and four showed slowing of ulnar nerve velocity at elbow. No patients developed neuropathy neither worsening of electrophysiological parameters during thalidomide treatment. The most common side effect was tremor, always reversible after withdrawing or reducing thalidomide. Paresthesias, somnolence, amenhorrea, constipation were also present. Only one patient had to stop the therapy for the occurrence, 10 days after taking 50 mg of thalidomide, of a severe, stabbing, "zoster-like" thoracic pain, which disappeared upon withdrawal of the drug. Started again on thalidomide, the symptoms reappeared and the patient definitely interrupted the therapy with benefit. All the 11 patients who continued on the therapy presented a significant improvement or remission of the cutaneous alterations. These preliminary data seem to indicate that low dose thalidomide is efficacious and tolerable for cutaneous lupus erythematosus. Peripheral neuropathy seems not to be a major side effect. A longer follow-up and the study of more patients are needed to confirm the results. [source] Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: A randomized, double-blind trialACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2004G. Dierking Background: Preliminary clinical studies have suggested that gabapentin may produce analgesia and reduce the need for opioids in postoperative patients. The aim of the present study was to investigate the opioid-sparing and analgesic effects of gabapentin administered during the first 24 h after abdominal hysterectomy. Methods: In a randomized, double-blind study, 80 patients received oral gabapentin 1200 mg or placebo 1 h before surgery, followed by oral gabapentin 600 mg or placebo 8, 16 and 24 h after the initial dose. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 24 h postoperatively. Pain was assessed on a visual analogue scale (VAS) at rest and during mobilization, nausea, somnolence and dizziness on a four-point verbal scale, and vomiting as present/not present at 2, 4, 22 and 24 h postoperatively. Results: Thirty-nine patients in the gabapentin group, and 32 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from median 63 (interquartile range 53,88) mg to 43 (28,60) mg (P < 0.001). We observed a significant inverse association between plasma levels of gabapentin at 2 h postoperatively, and morphine usage from 0 to 2 h, and from 0 to 4 h postoperatively (R2 = 0.30, P = 0.003 and R2 = 0.24 P = 0.008, respectively). No significant differences in pain at rest or during mobilization, or in side-effects, were observed between groups. Conclusion: Gabapentin in a total dose of 3000 mg, administered before and during the first 24 h after abdominal hysterectomy, reduced morphine consumption with 32%, without significant effects on pain scores. No significant differences in side-effects were observed between study-groups. [source] Double-blind study of pardoprunox, a new partial dopamine agonist, in early Parkinson's disease,MOVEMENT DISORDERS, Issue 6 2010Juliana Bronzova MD Abstract This study examined the efficacy and safety of the partial dopamine agonist, pardoprunox (SLV308), in the treatment of patients with early Parkinson's disease (PD). Patients were randomized to receive pardoprunox (n = 69) or placebo (n = 70). Pardoprunox was titrated to each patient's optimal dose (9,45 mg/d) over 2 to 6 weeks and then maintained at this dose for a further 3 weeks. Concomitant anti-Parkinson treatment was not permitted. In the primary analysis, Unified PD Rating Scale (UPDRS)-Motor score was improved in pardoprunox-treated patients (overall mean dose 23.8 mg/d; ,7.3 points), as compared with placebo (,3.0 points; P = 0.0001), from baseline to end point. At end point, there were more responders (,30% reduction in UPDRS-Motor score) in the pardoprunox group (50.7%) than in the placebo group (15.7%; P < 0.0001). In other secondary analyses, UPDRS-activities of daily living (ADL) and -ADL+Motor scores were also significantly more improved in the pardoprunox group. Nausea was reported by 32 of 68 (47.1%) pardoprunox-treated patients (vs. 3/70, 4.3%, placebo-treated patients), with dizziness, somnolence, headache, and asthenia also reported by ,10 patients. In this exploratory proof-of-concept study, pardoprunox significantly improved motor function in patients with early PD. The efficacy and safety profile of pardoprunox justifies its further investigation in PD. © 2010 Movement Disorder Society [source] An open-label conversion study of pramipexole to ropinirole prolonged release in Parkinson's disease,MOVEMENT DISORDERS, Issue 14 2009Kelly E. Lyons PhD Abstract Ropinirole prolonged release (PR) is a once daily oral dopamine agonist approved for the treatment of Parkinson's disease (PD). The goal of this 4 week, open-label study was to determine the most effective conversion ratio with the fewest adverse effects (AEs) when switching from pramipexole to ropinirole PR. Sixty patients with PD taking pramipexole were converted overnight to ropinirole PR at ratios of 1:3, 1:4, or 1:5 such that 20 consecutive subjects were enrolled in each group. Ropinirole PR dose adjustments were allowed to maintain efficacy or to reduce AEs. An overnight switch from pramipexole to ropinirole PR was found to be well tolerated and AEs were typical for a dopamine agonist. The most common AEs were worsening of PD symptoms, dizziness, somnolence, and nausea, the majority of which resolved after dose adjustments. Thirteen subjects discontinued ropinirole PR before 4 weeks. These subjects were taking a significantly greater dose of pramipexole, the majority greater than 4 mg/day, and tended to have longer disease durations. A conversion ratio of 1 mg of pramipexole to 4 mg of ropinirole PR resulted in the fewest discontinuations of ropinirole PR, the fewest dose adjustments and the largest percentage of subjects that preferred ropinirole PR. © 2009 Movement Disorder Society [source] Dopamine receptor gene polymorphisms in Parkinson's disease patients reporting "sleep attacks"MOVEMENT DISORDERS, Issue 11 2004Ida Rissling MD Abstract Genes encoding proteins involved in dopaminergic transmission are potential candidate genes for the induction of somnolence in Parkinson's disease (PD) because dopaminergic agents have been shown to be associated with sudden onset of sleep (SOS) in PD. We conducted an association study on dopamine D2, D3, and D4 receptor gene polymorphisms comparing 137 PD patients with SOS and 137 PD patients without SOS matched according to drug therapy, disease duration, sex, and age. Our results show a significant association between the dopamine D2 receptor gene polymorphism Taq IA and SOS in PD. No significant association between two other investigated polymorphisms and the phenomenon of "sleep attacks" in PD was observed. © 2004 Movement Disorder Society [source] | ||||||||||||||||||||||||||||||||||