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Acute Treatment (acute + treatment)
Selected AbstractsA Randomized Controlled Trial of Mist in the Acute Treatment of Moderate CroupACADEMIC EMERGENCY MEDICINE, Issue 9 2002Gina M. Neto MD Abstract Objective: To determine whether the use of mist improves clinical symptoms in children presenting to the emergency department (ED) with moderate croup. Methods: Children 3 months to 6 years of age were eligible for the study if they presented to the ED with moderate croup. Moderate croup was defined as a croup score of 2-7. The patients were randomly assigned to receive either mist (humidified oxygen) via mist stick or no mist. The patients had croup scores measured at baseline and every 30 minutes for up to two hours. At these intervals the following parameters were also measured: heart rate, respiratory rate, oxygen saturation, and patient comfort score. The patients were treated until the croup score was less than 2 or until two hours had elapsed. All patients initially received a dose of oral dexamethasone (0.6 mg/kg). Other treatments, such as racemic epinephrine or inhaled budesonide, were given at the discretion of the treating physician. The research assistants were unaware of the assigned treatments. Results: There were 71 patients enrolled in the study; 35 received mist and 36 received no mist. The two treatment groups had similar characteristics at baseline. The median baseline croup score was 4 in both groups. The outcomes were measured as the change from baseline at 30, 60, 90, and 120 minutes. The change in the croup score from baseline in the mist group was not statistically different from the croup score change in the group that did not receive mist (p = 0.39). There was also no significant difference in improvement of oxygen saturation, heart rate, or respiratory rate at any of the assessment times. There was no adverse effect from the mist therapy. Conclusions: Mist therapy is not effective in improving clinical symptoms in children presenting to the ED with moderate croup. [source] Electrical Stimulation of Sphenopalatine Ganglion for Acute Treatment of Cluster HeadachesHEADACHE, Issue 7 2010Mehdi Ansarinia MD (Headache 2010;50:1164-1174) Introduction., Cluster headaches (CH) are primary headaches marked by repeated short-lasting attacks of severe, unilateral head pain and associated autonomic symptoms. Despite aggressive management with medications, oxygen therapy, nerve blocks, as well as various lesioning and neurostimulation therapies, a number of patients are incapacitated and suffering. The sphenopalatine ganglion (SPG) has been implicated in the pathophysiology of CH and has been a target for blocks, lesioning, and other surgical approaches. For this reason, it was selected as a target for an acute neurostimulation study. Methods., Six patients with refractory chronic CH were treated with short-term (up to 1 hour) electrical stimulation of the SPG during an acute CH. Headaches were spontaneously present at the time of stimulation or were triggered with agents known to trigger clusters headache in each patient. A standard percutaneous infrazygomatic approach was used to place a needle at the ipsilateral SPG in the pterygopalatine fossa under fluoroscopic guidance. Electrical stimulation was performed using a temporary stimulating electrode. Stimulation was performed at various settings during maximal headache intensity. Results., Five patients had CH during the initial evaluation. Three returned 3 months later for a second evaluation. There were 18 acute and distinct CH attacks with clinically maximal visual analog scale (VAS) intensity of 8 (out of 10) and above. SPG stimulation resulted in complete resolution of the headache in 11 attacks, partial resolution (>50% VAS reduction) in 3, and minimal to no relief in 4 attacks. Associated autonomic features of CH were resolved in each responder. Pain relief was noted within several minutes of stimulation. Conclusion., Sphenopalatine ganglion stimulation can be effective in relieving acute severe CH pain and associated autonomic features. Chronic long-term outcome studies are needed to determine the utility of SPG stimulation for management and prevention of CH. [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] Eletriptan for the Acute Treatment of Migraine in Adolescents: Results of a Double-Blind, Placebo-Controlled TrialHEADACHE, Issue 4 2007Paul Winner DO Background.,Eletriptan is a potent 5-HT1B/1D agonist with proven efficacy in the acute treatment of migraine in adults. Objective.,To evaluate the efficacy and tolerability of eletriptan 40 mg versus placebo in adolescent patients (aged 12-17). Methods.,A multicenter, double-blind, parallel-group, placebo-controlled trial was conducted comparing 40 mg of oral eletriptan with placebo for the treatment of migraine in adolescent patients. The primary efficacy endpoint was 2-hour headache response, and a number of secondary endpoints were also evaluated. An exploratory analysis evaluated which clinical and demographic characteristics might be correlated with high placebo response. Results.,Of 274 patients who treated a migraine attack, 267 were evaluated for efficacy (n = 138 eletriptan; n = 129 placebo) at 2 hours post-dose. There was no significant difference in 2-hour headache response for eletriptan 40 mg versus placebo (57% vs 57%), and no significant improvements were observed for any of the outcomes at 1 or 2 hours post-dose. By contrast, there was a significant advantage for eletriptan 40 mg in reducing headache recurrence within 24 hours post-dose (11% vs 25%, P= .028), and post hoc analyses showed statistically significant differences for sustained headache response rates (52% vs 39%; P= .04) and sustained pain-free response rates (22% vs 10%; P= .013). The strongest clinical predictor of placebo response was triptan-naïve status (ie, no previous use of any triptan). Eletriptan 40 mg was well tolerated in this population, and the profile of adverse events was similar to that observed in Phase III trials in adult patients. Conclusions.,The high placebo response rates reported here for 1- and 2-hour outcomes are in accordance with other studies of triptans in adolescent patients. The evaluation of treatment effect in adolescent migraine might benefit from use of more stringent outcome measures, such as headache recurrence, sustained headache response, and sustained pain-free response at 24 hours post-dose. [source] Introduction: Cardiovascular Safety and Triptans in the Acute Treatment of MigraineHEADACHE, Issue 2004David W. Dodick MD First page of article [source] Pharmacological Profile and Clinical Characteristics of Frovatriptan in the Acute Treatment of Migraine:HEADACHE, Issue 2002Introduction No abstract is available for this article. [source] Dose Range-Finding Studies With Frovatriptan in the Acute Treatment of MigraineHEADACHE, Issue 2002Alan Rapoport MD Objective.,To determine the optimum dose of frovatriptan for the acute treatment of migraine. Background.,Frovatriptan is a new triptan developed for the acute treatment of migraine. The dose-response characteristics and safety of frovatriptan have been investigated across a broad range of doses from 0.5 to 40 mg. Design.,Two randomized, placebo-controlled, double-blind, parallel-group trials, with a total of 1453 patients, were performed to determine the optimal dose of the 5-HT1B/1D agonist, frovatriptan, for the acute treatment of migraine. The dose ranges studied were 2.5 to 40 mg in the high-dose study and 0.5 to 5 mg in the low-dose study. Results.,At 2 hours postdosing for initial moderate or severe headache (International Headache Society grades 2 or 3), there was an approximate two-fold difference in the proportion of patients taking frovatriptan doses of 2.5 to 40 mg with mild or no headache compared to placebo. Frovatriptan doses of 0.5 mg and 1 mg were not more effective than placebo at 2 hours postdose, and 2.5 mg was identified as the lowest effective dose for the relief of migraine and accompanying symptoms. Above 2.5 mg, no dose-response relationship was observed for any efficacy parameters. There was an increase in the incidence of adverse events from 10 mg and above, but the vast majority were rated as mild in severity and did not impact upon tolerability in a significant manner. Conclusions.,Frovatriptan was well tolerated throughout the dose range of 0.5 to 40 mg. The 2.5-mg dose confers the optimal balance of efficacy and tolerability for the acute treatment of migraine. [source] Effects of six antihypertensive drugs on blood pressure and hypothalamic GABA content in spontaneously hypertensive ratsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2001Ying Guan In order to investigate the effects of antihypertensive drugs on blood pressure and ,-amino butyric acid (GABA) content in the hypothalamus and the possible relationship between blood pressure decrease and GABA content changes, blood pressure and GABA contents after chronic (20 weeks) treatments of nitrendipine, atenolol, captopril, hydrochlorothiazide, dihydralazine and prazosin were studied in spontaneously-hypertensive rats (SHR). The acute and subacute (1 week) effects of nitrendipine on GABA contents was also observed in SHR. It was found that 20 week treatments with six different antihypertensive agents produced a decrease in systolic blood pressure and an increase in GABA content. The blood pressure level was significantly correlated with GABA content in the hypothalamus, but not with that in the cortex. Acute treatment with a single dose of nitrendipine, did not alter GABA content. Bicuculline, a GABA receptor antagonist, did not attenuate the hypotensive effect of nitrendipine. In conclusion, chronic treatments by different antihypertensive agents produced an increase of hypothalamic GABA content and a decrease of blood pressure. The increase of GABA content induced by nitrendipine seems likely to be secondary to blood pressure decrease. [source] Acute treatment of paediatric migraine: A meta-analysis of efficacyJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 1-2 2008Shawna Silver Aim: To undertake a meta-analysis of all randomised controlled trials (RCTs) on the acute pharmacologic treatment of children and adolescents with migraine headache. Methods: In total, 139 abstracts of clinical trials specific to the acute treatment of paediatric migraine were appraised. Inclusion criteria required clinical trials to be randomised, blinded, placebo-controlled studies with comparable endpoints. Non- English language publications were excluded. 11 clinical trials qualified for inclusion in the final meta-analysis. Two endpoints were analysed: the proportion of patients with (1) headache relief, and (2) complete pain relief, 2 h post-treatment. Results: The following medications were included in the analysis: acetaminophen (n = 1), ibuprofen (n = 2), sumatriptan (n = 5), zolmitriptan (n = 1), rizatriptan (n = 2) and dihydroergotamine (n = 1). Results are expressed as a relative benefit (RB) conferred over placebo and the number needed to treat (NNT). Only ibuprofen and sumatriptan provided a statistically significant relative efficacy in comparison with placebo. Two hours post-treatment, ibuprofen was associated with an RB 1.50 (95% CI 1.15,1.95) in the generation of headache relief (NNT 2.4) and RB 1.92 (95% CI 1.28,2.86) in the production of complete pain relief (NNT 4.9). Sumatriptan rendered an RB 1.26 (95% CI 1.13,1.41) in headache relief (NNT 7.4) and an RB 1.56 (95% CI 1.26,1.93) in the production of complete pain relief (NNT 6.9). Conclusion: Despite the pharmacological options for the management of acute migraine, few RCTs in the paediatric population exist. Composite data demonstrate that only ibuprofen and sumatriptan are significantly more effective than placebo in the generation of headache relief in children and adolescents. [source] Melatonin ameliorates hippocampal nitric oxide production and large conductance calcium-activated potassium channel activity in chronic intermittent hypoxiaJOURNAL OF PINEAL RESEARCH, Issue 3 2008Y. W. Tjong Abstract:, Melatonin protects against hippocampal injury induced by intermittent hypoxia (IH). IH-induced oxidative stress is associated with decreases in constitutive production of nitric oxide (NO) and in the activity of large conductance calcium-activated potassium (BK) channels in hippocampal neurons. We tested the hypothesis that administration of melatonin alleviates the NO deficit and impaired BK channel activity in the hippocampus of IH rats. Sprague,Dawley rats were injected with melatonin (10 mg/kg, i.p.) or vehicle before daily IH exposure for 8 hr for 7 days. The NO and intracellular calcium ([Ca2+]i) levels in the CA1 region of hippocampal slices were measured by electrochemical microsenor and spectrofluorometry, respectively. The activity of BK channels was recorded by patch-clamping electrophysiology in dissociated CA1 neurons. Malondialdehyde levels were increased in the hippocampus of hypoxic rats and were lowered by the melatonin treatment. Levels of NO under resting and hypoxic conditions, and the protein expression of neuronal NO synthase (nNOS) were significantly reduced in the CA1 neurons of hypoxic animals compared with the normoxic controls. These deficits were mitigated in the melatonin-treated hypoxic rats with an improved [Ca2+]i response to acute hypoxia. The open probability of BK channels was decreased in the hypoxic rats and was partially restored in the melatonin-treated animals, without alterations in the expression of channel subunits and unitary conductance. Acute treatment of melatonin had no significant effects on the BK channel activity or on the [Ca2+]i response to hypoxia. Collectively, these results suggest that melatonin ameliorates the constitutive NO production and BK channel activity via an antioxidant mechanism against an IH-induced down-regulation of nNOS expression in hippocampal neurons. [source] Acute treatment of bipolar depression with adjunctive zonisamide: a retrospective chart reviewBIPOLAR DISORDERS, Issue 5 2004Claudia F Baldassano Background:, This retrospective chart review evaluated the use of zonisamide as adjunctive treatment in patients with bipolar depression. Method:, The charts of outpatients with bipolar I or II disorder treated with adjunctive zonisamide were reviewed. The efficacy of zonisamide was assessed via comparison of physician-rated Global Assessment of Functioning (GAF) and Clinical Global Impression of Severity (CGI-S) Scale scores at baseline and after 6 weeks of therapy using paired t -tests. Patients who scored ,2 on the CGI-S after 6 weeks of zonisamide therapy were considered good responders to zonisamide. Results:, Charts for 12 patients (four men and eight women) with a mean (±SD) age of 39.6 (±7.6) years were evaluated. Patients received a mean (±SD) zonisamide dosage of 236 (±68) mg/day. Mean GAF scores significantly improved from 44.0 at baseline to 59.3 at week 6 (P = 0.05). Mean CGI-S scores improved from 4.54 at baseline to 3.42 at week 6, but the change was not statistically significant. Six patients (50.0%) were considered responders to zonisamide. Four patients discontinued zonisamide therapy, two for an adverse event (sedation) and two for lack of efficacy. Conclusions:, Zonisamide may be a useful adjunctive treatment for some patients with bipolar depression. Conclusions from this study are limited due to its retrospective design. Further investigation of zonisamide in the treatment of bipolar depression is warranted. [source] Migraine: a review and future directions for treatmentACTA NEUROLOGICA SCANDINAVICA, Issue 2 2006M. Linde Migraine is a chronic, neurological disorder generally manifesting itself in attacks with severe headache, nausea and an increased reactivity to sensory stimuli. A low migraine threshold is set by genetic factors, although the phenotype also modulates the manifestations. The 1-year prevalence is approximately 13% and is higher among women. Patients usually experience neuropsychological dysfunction, and sometimes also reversible focal neurological symptoms. The trajectories of the characteristic symptoms of acute migraine usually follow a similar time course, indicating a reciprocal underlying mechanism. A central nervous system hyperexcitability has been demonstrated in neurophysiological studies. The dibilitating effects of migraine are not confined to the attacks per se. Many individuals do not recover completely between the attacks and most report a negative impact on the most important life domains, and an interest in testing other treatments. Young persons have a higher frequency of attacks. Acute treatment should routinely be initiated with an analgesic plus a prokinetic anti-emetic. Triptans must not be provided early during the attack to ensure their efficacy. The natural course of attacks is commonly only temporarily altered by acute treatment. Non-pharmacological treatment and drugs may be equally viable in prophylaxis for migraine. In more complicated cases, conjoint therapy should be considered. New strategies to improve adherence with existing therapeutic regimens might yield greater benefits than will new pharmacological agents. [source] C1 inhibitor deficiency: consensus documentCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2005M. M. Gompels Summary We present a consensus document on the diagnosis and management of C1 inhibitor deficiency, a syndrome characterized clinically by recurrent episodes of angio-oedema. In hereditary angio-oedema, a rare autosomal dominant condition, C1 inhibitor function is reduced due to impaired transcription or production of non-functional protein. The diagnosis is confirmed by the presence of a low serum C4 and absent or greatly reduced C1 inhibitor level or function. The condition can cause fatal laryngeal oedema and features indistinguishable from gastrointestinal tract obstruction. Attacks can be precipitated by trauma, infection and other stimulants. Treatment is graded according to response and the clinical site of swelling. Acute treatment for severe attack is by infusion of C1 inhibitor concentrate and for minor attack attenuated androgens and/or tranexamic acid. Prophylactic treatment is by attenuated androgens and/or tranexamic acid. There are a number of new products in trial, including genetically engineered C1 esterase inhibitor, kallikrein inhibitor and bradykinin B2 receptor antagonist. Individual sections provide special advice with respect to diagnosis, management (prophylaxis and emergency care), special situations (childhood, pregnancy, contraception, travel and dental care) and service specification. [source] Effect of treatment delay upon pulp and periodontal healing of traumatic dental injuries , a review articleDENTAL TRAUMATOLOGY, Issue 3 2002J.O. Andreasen Abstract,,,Based on an analysis of the literature concerning parameters influencing the prognosis of traumatic dental injuries, few studies were found to have examined possible relationships between treatment delay and pulpal and periodontal ligament healing complications. It has been commonly accepted that all injuries should be treated on an emergency basis, for the comfort of the patient and also to reduce wound healing complications. For practical and especially economic reasons, various approaches can be selected to fulfill such a demand, such as acute treatment (i.e. within a few hours), subacute (i.e. within the first 24 h), and delayed (i.e. after the first 24 h). In this survey the consequences of treatment delay on pulpal and periodontal healing have been analyzed for the various dental trauma groups. Applying such a treatment approach to the various types of injuries, the following treatment guidelines can be recommended, based on our present rather limited knowledge of the effect of treatment delay upon wound healing. Crown and crown/root fractures: Subacute or delayed approach. Root fractures: Acute or subacute approach. Alveolar fractures: Acute approach (evidence however questionable). Concussion and subluxation: Subacute approach. Extrusion and lateral luxation: Acute or subacute approach (evidence however questionable). Intrusion: Subacute approach (evidence however questionable). Avulsion: If the tooth is not replanted at the time of injury, acute approach; otherwise subacute. Primary tooth injury: Subacute approach, unless the primary tooth is displaced into the follicle of the permanent tooth or occlusal problems are present; in the latter instances, an acute approach should be chosen. These treatment guidelines are based on very limited evidence from the literature and should be revised as soon as more evidence about the effect of treatment delay becomes available. [source] Multidimensional effects of sertraline in social anxiety disorderDEPRESSION AND ANXIETY, Issue 1 2006Kathryn M. Connor M.D. Abstract Clinical trials of social anxiety disorder (SAD) have largely focused on the effect of treatment on symptoms of fear and avoidance, while neglecting the third clinically relevant dimension, physiological arousal. Data were combined from two previously reported placebo-controlled trials of sertraline in the treatment of moderate-to-severe generalized SAD. Efficacy was evaluated using the Brief Social Phobia Scale (BSPS). Three hundred forty-six subjects were randomized to 12,13 weeks of treatment with sertraline and 273 subjects to placebo. Following treatment, significant improvement was noted in favor of sertraline on the full BSPS (P<.001), as well as on each of the individual BSPS subscales: fear (P=.001); avoidance (P<.0001); and physiological arousal (P<.0001). Of the physiological symptoms assessed, the treatment advantage with sertraline was maintained for blushing (P<.003) and palpitations (P<.03), but not for trembling and sweating. These results confirm the efficacy of treatment with a selective serotonin reuptake inhibitor (SSRI), sertraline, across the spectrum of fear, avoidance, and physiological arousal in generalized SAD (GSAD). Among common physiological symptoms in this population, blushing and palpitations appear more treatment responsive than trembling and sweating to acute treatment with sertraline. Depression and Anxiety 23:6,10, 2006. © 2005 Wiley-Liss, Inc. [source] Effects of buspirone and alprazolam treatment on the startle-potentiated startle responseDEPRESSION AND ANXIETY, Issue 3 2004Randall L. Commissaris Ph.D. Abstract The startle potentiated startle (SPS) paradigm has been reported to be an effective procedure for studying the conditioned enhancement of acoustic startle in the absence of electric shocks or extinction. This study examines the effects of two anxiolytic treatments, buspirone and alprazolam, on this SPS effect. Subjects were tested in the SPS paradigm 2 days a week (Monday and Thursday) for 10 weeks. Each startle test session consisted of 10 Noise Alone trials (115 dB acoustic noise burst presented for 40 ms) and 10 Light+Noise trials (115 dB acoustic stimuli presented during the latter 40 ms of a 3,540 ms period in which a 15-watt light was illuminated). Although there was no difference in startle amplitude on Noise Alone trials when compared to Light+Noise trials initially, by the end of the first test session and continuing throughout the duration of the experiment, startle amplitude on Light+Noise trials was significantly (approximately 50,75%) greater than on Noise Alone trials. After five control (i.e., no injection) SPS test sessions, once-weekly drug challenges were conducted over the course of 7 weeks. In these weekly drug challenges, subjects received acute treatment with various doses of the benzodiazepine anxiolytic alprazolam (0.25, 0.5, 1.0 mg/kg) or the novel anxiolytic buspirone (1.0, 2.0, 4.0 mg/kg); subjects also received vehicle treatment (0.5% methylcellulose) on one treatment day. All treatments were administered intraperitoneally (IP), 15 min before the start of startle testing. Consistent with previous reports, buspirone increased and alprazolam decreased startle amplitude on the Noise Alone trials; these effects were dose-related. Both agents reduced the magnitude of the SPS effect when it was expressed as the Light+Noise startle amplitude minus the Noise Alone startle amplitude. These findings are similar to the effects of these treatments in the traditional shock-based fear-potentiated startle paradigm. Depression and Anxiety 19:146,151, 2004. © 2004 Wiley-Liss, Inc. [source] Activation of ADF/cofilin mediates attractive growth cone turning toward nerve growth factor and netrin-1DEVELOPMENTAL NEUROBIOLOGY, Issue 8 2010Bonnie M. Marsick Abstract Proper neural circuitry requires that growth cones, motile tips of extending axons, respond to molecular guidance cues expressed in the developing organism. However, it is unclear how guidance cues modify the cytoskeleton to guide growth cone pathfinding. Here, we show acute treatment with two attractive guidance cues, nerve growth factor (NGF) and netrin-1, for embryonic dorsal root ganglion and temporal retinal neurons, respectively, results in increased growth cone membrane protrusion, actin polymerization, and filamentous actin (F-actin). ADF/cofilin (AC) family proteins facilitate F-actin dynamics, and we found the inactive phosphorylated form of AC is decreased in NGF- or netrin-1-treated growth cones. Directly increasing AC activity mimics addition of NGF or netrin-1 to increase growth cone protrusion and F-actin levels. Extracellular gradients of NGF, netrin-1, and a cell-permeable AC elicit attractive growth cone turning and increased F-actin barbed ends, F-actin accumulation, and active AC in growth cone regions proximal to the gradient source. Reducing AC activity blunts turning responses to NGF and netrin. Our results suggest that gradients of NGF and netrin-1 locally activate AC to promote actin polymerization and subsequent growth cone turning toward the side containing higher AC activity. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 565,588, 2010 [source] Further characterization and validation of gpt delta transgenic mice for quantifying somatic mutations in vivoENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2001Roy R. Swiger Abstract The utility of any mutation assay depends on its characteristics, which are best discovered using model mutagens. To this end, we report further on the characteristics of the lambda-based gpt delta transgenic assay first described by Nohmi et al. ([1996]: Environ Mol Mutagen 28:465,470). Our studies show that the gpt transgene responds similarly to other transgenic loci, specifically lacZ and cII, after treatment with acute doses of N -ethyl- N -nitrosourea (ENU). Because genetic neutrality is an important factor in the design of treatment protocols for mutagenicity testing, as well as for valid comparisons between different tissues and treatments, a time-course study was conducted. The results indicate that the gpt transgene, like cII and lacZ, is genetically neutral in vivo. The sensitivities of the loci are also equivalent, as evidenced by spontaneous mutant frequency data and dose, response curves after acute treatment with 50, 150, or 250 mg/kg ENU. The results are interesting in light of transgenic target size and location and of host genetic background differences. Based on these studies, protocols developed for other transgenic assays should be suitable for the gpt delta. Additionally, a comparison of the gpt and an endogenous locus, Dlb-1, within the small intestine of chronically treated animals (94 ,g/mL ENU in drinking water daily) shows differential accumulation of mutations at the loci during chronic exposure. The results further support the existence of preferential repair at endogenous, expressed genes relative to transgenes. Environ. Mol. Mutagen. 37:297,303, 2001 © 2001 Wiley-Liss, Inc. [source] A modified MPTP treatment regime produces reproducible partial nigrostriatal lesions in common marmosetsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Mahmoud M. Iravani Abstract Standard MPTP treatment regimens in primates result in >,85% destruction of nigral dopaminergic neurons and the onset of marked motor deficits that respond to known symptomatic treatments for Parkinson's disease (PD). The extent of nigral degeneration reflects the late stages of PD rather than events occurring at its onset. We report on a modified MPTP treatment regimen that causes nigral dopaminergic degeneration in common marmosets equivalent to that occurring at the time of initiation of motor symptoms in man. Subcutaneous administration of MPTP 1 mg/kg for 3 consecutive days caused a reproducible 60% loss of nigral tyrosine hydroxylase (TH)-positive cells, which occurred mainly in the calbindin-D28k -poor nigrosomes with a similar loss of TH-immunoreactivity (TH-ir) in the caudate nucleus and the putamen. The animals showed obvious motor abnormalities with reduced bursts of activity and the onset of motor disability. However, the loss of striatal terminals did not reflect early PD because a greater loss of TH-ir occurred in the caudate nucleus than in the putamen and a marked reduction in TH-ir occurred in striatal patches compared to the matrix. Examination of striatal fibres following a partial MPTP lesion showed a conspicuous increase in the number and the diameter of large branching fibres in the putaminal and to some extent caudatal matrix, pointing to a possible compensatory sprouting of dopaminergic terminals. In addition, these partially lesioned animals did not respond to acute treatment with L-DOPA. This primate partial lesions model may be useful for examining potential neuroprotective or neurorestorative agents for PD. [source] PDE10A inhibition reverses subchronic PCP-induced deficits in attentional set-shifting in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005Joshua S. Rodefer Abstract Persistent suppression of N -methyl- d -aspartate (NMDA) receptor function produces enduring structural changes in neocortical and limbic regions in a pattern similar to changes reported in schizophrenia. This similarity suggests that chronic NMDA receptor antagonism in animals may represent a useful model of neurobiological and related cognitive deficits in schizophrenia. Schizophrenia is associated with impairments in frontal lobe-dependent cognitive functions, including working memory and attentional shifting. Deficits in attention and executive function have not been well characterized in animal models of schizophrenia using chronic NMDA receptor antagonist administration. We investigated whether subchronic systemic administration of the NMDA receptor antagonist phencyclidine (PCP) to rats followed by a drug washout period would produce enduring cognitive deficits on an attentional set-shifting task. The task is functionally analogous to a sensitive test of frontal function in humans and non-human primates. Subchronic PCP administration selectively impaired extradimensional shift learning without affecting other discrimination or reversal tasks. Moreover, acute treatment with the PDE10A inhibitor papaverine immediately prior to testing attenuated the PCP-induced deficits in extradimensional shift learning across a range of doses. These data suggest that subchronic PCP administration may model effectively some of the cognitive deficits that are observed in schizophrenia, and that PDE10A inhibition may be an effective therapeutic route to improve executive function deficits associated with schizophrenia. [source] Hyperbaric Oxygen Does Not Prevent Neurologic Sequelae after Carbon Monoxide PoisoningACADEMIC EMERGENCY MEDICINE, Issue 1 2002Benjamin Gilmer MS Abstract Delayed neurologic sequelae occur in up to 40% of severe carbon monoxide (CO) poisonings. Conflicting clinical data support the efficacy of hyperbaric oxygen (HBO) therapy in the acute treatment of CO poisoning. Objective: To determine whether oxygen therapy reduces neurologic sequelae after CO poisoning in mice. Methods: Male Swiss-Webster mice were exposed to CO at 1,000 ppm for 40 minutes and then 50,000 ppm until loss of consciousness (LOC) (4-9 additional minutes). Total time of both phases of CO exposure was 40-49 minutes. Treatment included HBO with 3 atmospheres (ATA) 100% oxygen, normobaric oxygen (NBO) with 1 ATA 100% oxygen, or ambient air 15 minutes after LOC. All animals underwent passive avoidance training and memory was assessed by measuring step-down latency (SDL) and step-up latency (SUL) seven days following CO exposure. Results: Carbon monoxide poisoning induced significant memory deficits (SDLCO= 156 sec; SULCO= 75%) compared with nonpoisoned (NP) animals (SDLNP= 272 sec; SULNP= 100%). Both HBO and NBO did not prevent these neurologic sequelae. Furthermore, no significant neurobehavioral differences were found between HBO and NBO. Histologic examination of the CA1 layer of the hippocampus for pyknotic cells showed significant damage from CO in the air-treated animals (9.6%) but not in the nonpoisoned animals (3.8%). No significant neuroprotection was seen histologically with NBO and HBO compared with ambient air. Conclusions: These results suggest that HBO is not effective in preventing neurologic sequelae in mice and that there is no benefit of HBO over NBO following severe CO neurotoxicity. [source] Diabetes hyperglycemia and recovery from strokeGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1-2 2001Christopher S Gray Strokeis a major cause of death and severe disability in older people. Despite the burden of disease, there is still no safe, simple and proven medical therapy for the treatment of acute stroke. Advances in acute stroke treatment have been either consistently disappointing (neuroprotective therapy) or fraught with controversy regarding risk/benefit (thrombolysis), and attention is once again being directed towards physiological variables that may influence outcome. Both insulin-dependent and non-insulin-dependent diabetes mellitus are major risk factors for stroke. Diabetes mellitus has also been shown to be associated with increased mortality and reduced functional outcome after stroke. Hyperglycemia is a frequent finding following stroke and may reflect the metabolic stress of the acute event, so-called stress hyperglycemia, and/or underlying impaired glucose metabolism. Several large clinical studies have now demonstrated a positive association between a raised blood glucose and poor outcome from stroke; greater mortality and reduced functional recovery. What is not clear is to what extent hyperglycemia is a ,normal' physiological response to stroke or whether hyperglycemia per se increases cerebral damage in the acute phase. There are many potential mechanisms by which hyperglycemia can exert a harmful effect upon cerebral tissue and it is probable that an important relationship exists, not only between glucose and stroke outcome, but also between insulin and neuroprotection. It remains to be determined whether lowering and maintaining ,normal' glucose levels in the immediate aftermath of stroke, combined with the administration of insulin as an acute treatment, can modify this outcome. [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] Migraine Disability Awareness Campaign in Asia: Migraine Assessment for ProphylaxisHEADACHE, Issue 9 2008Shuu-Jiun Wang MD Objectives., This study aimed to survey the headache diagnoses and consequences among outpatients attending neurological services in 8 Asian countries. Methods., This survey recruited patients who consulted neurologists for the first time with the chief complaint of headache. Patients suffering from headaches for 15 or more days per month were excluded. Patients answered a self-administered questionnaire, and their physicians independently completed a separate questionnaire. In this study, the migraine diagnosis given by the neurologists was used for analysis. The headache symptoms collected in the physician questionnaire were based on the diagnostic criteria of migraine proposed by the International Classification of Headache Disorders, second edition (ICHD-2). Results., A total of 2782 patients (72% females; mean age 38.1 ± 15.1 years) finished the study. Of them, 66.6% of patients were diagnosed by the neurologists to have migraine, ranging from 50.9% to 85.8% across different countries. Taken as a group, 41.4% of those patients diagnosed with migraine had not been previously diagnosed to have migraine prior to this consultation. On average, patients with migraine had 4.9 severe headaches per month with 65% of patients missing school, work, or household chores. Most (87.5%) patients with migraine took medications for acute treatment. Thirty-six percent of the patients had at least one emergency room consultation within one year. Only 29.2% were on prophylactic medications. Neurologists recommended pharmacological prophylaxis in 68.2% of patients not on preventive treatment. In comparison, migraine prevalence was the highest with ICHD-2 "any migraine" (ie, migraine with or without migraine and probable migraine) (73.3%) followed by neurologist-diagnosed migraine (66.6%) and ICHD-2 "strict migraine" (ie, migraine with or without aura only) (51.3%). About 88.6% patients with neurologist-diagnosed migraine fulfilled ICHD-2 any migraine but only 67.1% fulfilled the criteria of ICHD-2 strict migraine. Conclusions., Migraine is the most common headache diagnosis in neurological services in Asia. The prevalence of migraine was higher in countries with higher referral rates of patients to neurological services. Migraine remains under-diagnosed and under-treated in this region even though a high disability was found in patients with migraine. Probable migraine was adopted into the migraine diagnostic spectrum by neurologists in this study. [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] Eletriptan for the Acute Treatment of Migraine in Adolescents: Results of a Double-Blind, Placebo-Controlled TrialHEADACHE, Issue 4 2007Paul Winner DO Background.,Eletriptan is a potent 5-HT1B/1D agonist with proven efficacy in the acute treatment of migraine in adults. Objective.,To evaluate the efficacy and tolerability of eletriptan 40 mg versus placebo in adolescent patients (aged 12-17). Methods.,A multicenter, double-blind, parallel-group, placebo-controlled trial was conducted comparing 40 mg of oral eletriptan with placebo for the treatment of migraine in adolescent patients. The primary efficacy endpoint was 2-hour headache response, and a number of secondary endpoints were also evaluated. An exploratory analysis evaluated which clinical and demographic characteristics might be correlated with high placebo response. Results.,Of 274 patients who treated a migraine attack, 267 were evaluated for efficacy (n = 138 eletriptan; n = 129 placebo) at 2 hours post-dose. There was no significant difference in 2-hour headache response for eletriptan 40 mg versus placebo (57% vs 57%), and no significant improvements were observed for any of the outcomes at 1 or 2 hours post-dose. By contrast, there was a significant advantage for eletriptan 40 mg in reducing headache recurrence within 24 hours post-dose (11% vs 25%, P= .028), and post hoc analyses showed statistically significant differences for sustained headache response rates (52% vs 39%; P= .04) and sustained pain-free response rates (22% vs 10%; P= .013). The strongest clinical predictor of placebo response was triptan-naïve status (ie, no previous use of any triptan). Eletriptan 40 mg was well tolerated in this population, and the profile of adverse events was similar to that observed in Phase III trials in adult patients. Conclusions.,The high placebo response rates reported here for 1- and 2-hour outcomes are in accordance with other studies of triptans in adolescent patients. The evaluation of treatment effect in adolescent migraine might benefit from use of more stringent outcome measures, such as headache recurrence, sustained headache response, and sustained pain-free response at 24 hours post-dose. [source] Sumatriptan Nasal Spray in Adolescent Migraineurs: A Randomized, Double-Blind, Placebo-Controlled, Acute StudyHEADACHE, Issue 2 2006Paul Winner DO Objective.,To compare the efficacy and tolerability of sumatriptan nasal spray (NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subjects. Background.,Currently, no triptan is approved in the United States for the treatment of migraine in adolescent subjects (12 to 17 years). In a previous randomized, placebo-controlled study of 510 adolescent subjects, sumatriptan NS at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy analysis for headache relief with 20 mg at 2 hours did not demonstrate statistical significance (P= .059). A second study was initiated to evaluate the efficacy of sumatriptan NS in this population. Methods.,This was a randomized (1:1:1), placebo-controlled, double-blind, parallel-group study. Overall, 738 adolescent subjects (mean age: 14 years) with ,6-month history of migraine (with or without aura) self-treated a single attack of moderate or severe migraine. The primary endpoints were headache relief at 1 hour and sustained relief from 1 to 24 hours. Pain-free rates, presence/absence of associated symptoms, headache recurrence, and use of rescue medications were also assessed. Tolerability was based on adverse events (AEs) and vital signs. Results.,Sumatriptan NS 20 mg provided greater headache relief than placebo at 30 minutes (42% vs. 33%, respectively; P= .046) and 2 hours (68% vs. 58%; P= .025) postdose, but did not reach statistical significance at 1 hour (61% vs. 52%; P= .087) or for sustained headache relief from 1 to 24 hours (P= .061). Significant differences (P < .05) in favor of sumatriptan NS 20 mg over placebo were observed for several secondary efficacy endpoints including sustained relief from 2 to 24 hours. In general, sumatriptan NS 5 mg percentages were slightly higher than placebo but the differences did not reach statistical significance. Both doses of sumatriptan NS were well tolerated. No AEs were serious or led to study withdrawal. The most common event was taste disturbance (2%, placebo; 19%, sumatriptan NS 5 mg; 25%, sumatriptan NS 20 mg). Conclusions.,This study suggests that sumatriptan may be beneficial to some adolescents and is generally well tolerated in the acute treatment of migraine in this population. [source] Assessment of Adverse Events Associated With Triptans,Methods of Assessment Influence the ResultsHEADACHE, Issue 10 2004Fred D. Sheftell MD Background.,A recent study conducted in triptan-naïve migraine patients showed that tolerability was the second most important attribute of an acute treatment. However, the proportion of patients reporting side effects after any acute treatment may vary with regard to the method of assessment. Objectives.,To contrast two methods of assessing adverse events (prompted and unprompted) in those with headache using triptans. Methods.,This study was conducted in two sites, a headache center in the United States, and a neurology office focusing on headache in Italy. We prospectively surveyed 415 adults with headache, who had been using the same triptan for at least 3 months. Participants were asked about their headache and treatment history. Subjects then completed a standardized questionnaire, assessing adverse events in two different ways. First, subjects were asked if they had any adverse events when using the triptan. After returning the first part of the questionnaire, subjects received a second form, where 49 possible adverse events were listed. We contrasted and correlated both sets of answers. Results.,Most patients (U.S. = 74.9%, Italy = 65.5%) reported no side effects in the unprompted questionnaire. However, most of them (U.S. = 62.9%, Italy = 54.1%) reported at least one side effect in the prompted questionnaire. Most patients that reported side effects in the unprompted questionnaire said they had just one adverse event, while most reported two or more side effects in the prompted questionnaire. Both in the unprompted and in the prompted questionnaires, most side effects were rated as mild or moderate. Interestingly, 31 (7.5%) subjects (pooling data from both sites together) graded their adverse events as severe in the prompted questionnaire, but had not self-reported them. Conclusions.,(1) When assessing adverse events, the method of data collection may dramatically influence the results. (2) From those subjects who did not self-report adverse events after using a triptan, most of them will report positively if presented with a list of side effects. [source] Cluster headache: the challenge of clinical trials.HEADACHE, Issue 3 2003K Moore Curr Pain Headache. Rep 2002 Feb;6(1):52-56 The design and execution of clinical trials poses special problems for cluster headache. Although there is less inter-individual and intra-individual variability of attacks than seen with migraine, the brevity of attacks, spontaneous remissions unrelated to treatment, and the relative rarity of cluster headaches challenge investigators. The International Headache Society has developed guidelines that represent a compromise between scientific rigor and practicality. Only injectable sumatriptan for acute attacks and verapamil for prophylaxis have demonstrated a robust therapeutic effect in controlled clinical trials. Comment: Kenneth Moore raises important methodological considerations. It is possible to undertake crossover trials comparing different active treatments? He is correct in his assertion that few agents show robust efficacy. A major issue relates to the proportion of patients with episodic versus chronic cluster headache where efficacy of active treatments can vary. For example, oral zolmitriptan was effective against placebo only in those patients with episodic disease (Bahra A, Gawel MJ, Hardebo JE, Millson DS, Breen SA, Goadsby PJ. Oral zolmitriptan is effective in the acute treatment of cluster headache. Neurology. 2000;54:1832-1839). And a set of small studies on melatonin and cluster demonstrate the problems Dr. Moore describes. In one study (Leone M, D'Amico D, Moschiano F, Fraschini F, Busonne G. Metalonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups. Cephalalgia. 1996;16:494-496), the melatonin worked only in episodic, not chronic cluster patients. In the second study (Prinsheim T, Magnoux E, Dobson CF, Hamel E, Aube M. Melatonin as adjuctive therapy in the prophylaxis of cluster headache: a pilot study. Headache. 2002;42:787-792), melatonin did not work better than placebo in either episodic or chronic cluster patients. Furthermore, the paper abstracted above by Torelli and Manzoni suggests that episodic cluster may progress to chronic cluster as a result of extrinsic factors such as smoking. Finally, there are ethical issues in placebo-controlled cluster studies, given the severity of the pain and the availability of effective acute and chronic treatments. As noted above, Dr. Peter Goadsby points out the need to persevere with these studies to find nonvasoactive treatments for patients with cluster headache. DSM and SJT [source] | |||||||||||||||||||||||||||||||||||||