Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group

OBJECTIVE: To assess the safety and efficacy of botulinum toxin type A (BOTOX; Allergan, Inc) in the prevention of migraine. BACKGROUND: Current migraine preventive therapies are often unsatisfactory because of their limited efficacy, adverse effects, and drug interactions. Botulinum toxin type A injections often reduce the pain associated with conditions such as cervical dystonia, achalasia, rectal fissures, and myofascial pain syndrome. An open-label, noncontrolled study of botulinum toxin type A suggested benefits for patients with migraine. DESIGN AND METHODS: This was a double-blind, vehicle-controlled study of 123 subjects with a history of two to eight moderate-to-severe migraine attacks per month, with or without aura. Participants were randomized to receive single administrations of vehicle or botulinum toxin type A, 25 U or 75 U, injected into multiple sites of pericranial muscles at the same visit. During a 1-month baseline period and for 3 months following injection, subjects kept daily diaries in which they recorded migraine frequency, migraine severity, and the occurrence of migraine-associated symptoms. RESULTS: Compared with vehicle treatment, subjects in the 25-U botulinum toxin type A treatment group showed significantly fewer migraine attacks per month, a reduced maximum severity of migraines, a reduced number of days using acute migraine medications, and reduced incidence of migraine-associated vomiting. Both the 25-U and 75-U botulinum toxin type A groups were significantly better than the vehicle group on subject global assessment. Botulinum toxin A treatment was well tolerated, with only the 75-U treatment group exhibiting a significantly higher rate of treatment-related adverse events than vehicle. CONCLUSIONS: Pericranial injection of botulinum toxin type A, 25 U, was found to be a safe treatment that significantly reduced migraine frequency, migraine severity, acute medication usage, and associated vomiting.     

Efficacy and tolerability of prochlorperazine buccal tablets in treatment of acute migraine

OBJECTIVES: To study the efficacy and tolerability of prochlorperazine (PCZ) management of acute migraine. DESIGN AND METHODS: A double blind comparative study was conducted to assess the efficacy of buccal PCZ 3 mg compared with oral ergotamine tartarate 1 mg plus caffeine 100 mg (ERG) or placebo (buccal or oral) for treatment of acute migraine. In all, 114 episodes of acute migraine were evaluated. Patients graded symptoms on a four-point scale before and up to 4 hours after treatment. The primary efficacy parameters included headache resolution within 2 hours (grade 3 or 2 to grade 0) and alleviation of other accompanying symptoms of migraine. The supplementary endpoints included improvement in quality of life (QOL). RESULTS: The percentage of patients reporting resolution of headache (to grade 0) was 51.4% for buccal PCZ and 21.7% for buccal placebo, 23.1% for oral ERG and 28.6% for oral placebo, headache tended to recur in both the placebo and ERG groups after initial improvement. Buccal PCZ was well tolerated; no signs of local irritation were evident, and patients found the formulation easy to use. Mild but transient sedation and drowsiness were observed in 41%. CONCLUSIONS: In the present study, PCZ 3 mg via the buccal route produced faster improvement and greater efficacy than placebo (oral as well as buccal) or oral ERG. The global QOL score 2 hours after treatment scores was higher in the PCZ group. Buccal PCZ may represent a particularly effective alternative for acute migraine treatment.     

Quality-of-life assessment in patients with hyperhidrosis before and after treatment with botulinum toxin: results of an open-label study

BACKGROUND: Patients with hyperhidrosis, a disorder characterized by increased sweat production, experience substantial functional and emotional problems. Botulinum toxin type A (BTX-A) has been shown to be useful in the treatment of hyperhidrosis; however, few studies have considered the effects of treatment on patients' quality of life (QOL). OBJECTIVES: The objectives of this study were to assess QOL in patients with focal hyperhidrosis; to investigate whether the impairment in QOL in these patients is related to the type of hyperhidrosis or the number of sites involved; and to compare the changes in QOL and the response to BTX-A treatment in patients with axillary and palmar hyperhidrosis. METHODS: Patients with focal primary hyperhidrosis of the axillae, palms, and soles who had experienced decreased QOL and whose condition had not responded to conventional topical and physical therapies were included in this open-label study. Patients completed a self-administered Dermatology Life Quality Index (DLQI) questionnaire before and 2 weeks after treatment with BTX-A. RESULTS: All 41 patients had experienced a decrease in QOL as measured by the DLQI. The impairement in QOL was not dependent on the number or types of sites involved. Treatment with BTX-A led to improvement in QOL in all patients, with the median DLQI score decreasing (ie, improving) significantly from pretreatment level (P < 0.001). The improvement in QOL and response to treatment were similar in patients with axillary and palmar hyperhidrosis. CONCLUSIONS: Further studies with a longer follow-up period are needed to assess the long-term effects of BTX-A; however, preliminary data from the present study suggest that BTX-A improves QOL in patients with focal hyperhidrosis, independent of the presenting clinical picture.     

Exploding vs. imploding headache in migraine prophylaxis with Botulinum Toxin A

Migraine headache is routinely managed using medications that abort attacks as they occur. An alternative approach to migraine management is based on prophylactic medications that reduce attack frequency. One approach has been based on local intramuscular injections of Botulinum Toxin Type A (BTX-A). Here, we explored for neurological markers that might distinguish migraine patients who benefit from BTX-A treatment (100 units divided into 21 injections sites across pericranial and neck muscles). Responders and non-responders to BTX-A treatment were compared prospectively (n=27) and retrospectively (n=36) for a host of neurological symptoms associated with their migraine. Data pooled from all 63 patients are summarized below. The number of migraine days per month dropped from 16.0+/-1.7 before BTX-A to 0.8+/-0.3 after BTX-A (down 95.3+/-1.0%) in 39 responders, and remained unchanged (11.3+/-1.9 vs. 11.7+/-1.8) in 24 non-responders. The prevalence of aura, photophobia, phonophobia, osmophobia, nausea, and throbbing was similar between responders and non-responders. However, the two groups offered different accounts of their pain. Among non-responders, 92% described a buildup of pressure inside their head (exploding headache). Among responders, 74% perceived their head to be crushed, clamped or stubbed by external forces (imploding headache), and 13% attested to an eye-popping pain (ocular headache). The finding that exploding headache was impervious to extracranial BTX-A injections is consistent with the prevailing view that migraine pain is mediated by intracranial innervation. The amenability of imploding and ocular headaches to BTX-A treatment suggests that these types of migraine pain involve extracranial innervation as well.     

Botulinum toxin type-A therapy in cluster headache: an open study

The objective of this open single-centre study was to evaluate the efficacy and tolerability of botulinum toxin type-A (BTX-A) as add-on in the prophylactic treatment of cluster headache (CH). Twelve male patients with episodic (n=3) or chronic (n=9) CH, unresponsive to common prophylactic medications, were treated with a cumulative dose of 50 International Units (IU) BTX-A according to a standardised injection scheme into the ipsilateral pericranial muscles. One patient with chronic CH experienced a total cessation of attacks and in 2 patients attack intensity and frequency improved. In another patient with chronic CH typical attacks were not influenced, but an ipsilateral continuous occipital headache significantly improved. Patients with episodic CH did not benefit from BTX-A treatment. Tolerability was excellent. These findings provide evidence that BTX-A may be beneficial as an add-on prophylactic therapy for a limited number of patients with chronic CH.     

Symptomatic relief of migraine: multicenter comparison of Cafergot P-B, Cafergot, and placebo

A multicenter, randomized, double-blind trial was conducted to compare the efficacy of Cafergot P-B with that of its components, Cafergot, pentobarbital, and Bellafoline, and with placebo for the treatment of migraine. Patients with vascular headaches of the migraine type who regularly experienced nervous tension and some form of gastrointestinal distress with their headaches were randomized to one of five treatment groups. They were given treatment packets containing their assigned drug for use during two separate migraine attacks. Patients made pretreatment evaluations of the following symptoms: head pain, nervous tension, nausea, vomiting, anorexia, abdominal cramps, and photophobia. They made posttreatment evaluations of these symptoms 0.5, 1.0, 1.5, 2.0, and 3.0 hours after ingesting their assigned drug. Improvement scores were calculated from the differences between the pretreatment and the posttreatment ratings. Patients also made a final global assessment of their drug's efficacy. All patients who took at least one dose of the study medication and completed a baseline evaluation and at least one postdose evaluation of severity of pain were included in the analysis (n = 254). The comparisons of particular interest were those between Cafergot P-B and Cafergot and between Cafergot P-B and placebo. Cafergot P-B was significantly more effective than Cafergot in relieving head pain at hours 2 and 3, nervous tension, nausea, vomiting, anorexia, and photophobia. Cafergot P-B was significantly more effective than placebo in relieving head pain, nervous tension, nausea (second headache only), vomiting, and photphobia. The incidence of reported adverse effects was no greater with Cafergot P-B than with Cafergot; however, patients given Cafergot P-B reported less vomiting than did patients given Cafergot. The results of this study show that addition of pentobarbital and Bellafoline to Cafergot provides greater relief of pain, vomiting, nervous tension, photophobia, and other symptoms associated with migraine, while reducing the severity of the nausea that may accompany a migraine headache or Cafergot therapy.     

A preliminary comparison of the efficacy and tolerability of botulinum toxin serotypes A and B in the treatment of myofascial pain syndrome: a retrospective, open-label chart review

BACKGROUND: Myofascial pain syndrome (MPS) is characterized by acute or chronic regional muscle pain associated with single or multiple trigger points within taut bands of muscle. Botulinum toxins have clinical utility when sustained focal muscle relaxation is required and may be a useful addition to the treatment armamentarium for MPS. OBJECTIVE: The purpose of the present article was to compare the efficacy and tolerability of botulinum toxin serotypes A and B (BTX-A and BTX-B) in the treatment of MPS. METHODS: This was a retrospective, open-label, single-center chart review. Charts of all patients who received either BTX-A or BTX-B for MPS between January and November 2001 were included in the review. Patients rated the intensity of their pain on a visual analog scale (VAS) from 0 = no pain to 10 = worst pain imaginable before and after receiving BTX-A or BTX-B. RESULTS: The charts of 91 patients (74.7% female, 25.3% male; mean [SD] age, 47 [10.2] years) who received BTX-A (n = 56; mean dose, 256.9 U; range, 100-600 U) or BTX-B (n = 35; mean dose, 9000 U; range, 2500-20,000 U) were included in this retrospective review. Patients who received BTX-A had significantly greater mean reductions in VAS pain scores compared with those who received BTX-B (mean reduction, 2.7 vs 1.8, respectively; P < 0.001). Patients who received BTX-A also reported significantly longer durations of pain relief compared with those who received BTX-B (4.5 vs 2.7) months; P < 0.001). Eight of 56 patients (14.3%) in the group that received BTX-A reported mild adverse events that included flulike symptoms, injection-site pain, and weakness of the neck muscles. Seven of 35 patients (20.0%) in the group that received BTX-B reported adverse events that included mild flulike symptoms, dry eyes, severe visual disturbances, and severe dry mouth. CONCLUSION: Patients with MPS who received BTX-A reported significantly greater reductions in pain for longer durations compared with those who received BTX-B. No patients who received BTX-A experienced severe systemic adverse events, compared with 4 patients who received BTX-B. The results of this comparison are consistent with the US Food and Drug Administration-approved labeling indicating that BTX-A is not interchangeable with any other botulinum toxin in terms of biological activity.     

A randomized open-label study of sodium valproate vs sumatriptan and metoclopramide for prolonged migraine headache

ObjectiveThe objective of this study is to compare the efficacy and tolerability of intravenous valproic acid (iVPA) with intramuscular metoclopramide + subcutaneous (SQ) sumatriptan for prolonged acute migraine.BackgroundIntravenous valproic acid has been explored as a possible treatment of acute migraine. Sumatriptan and newer generation triptans are also effective for migraine. However, iVPA has not yet been compared with triptans in head-to-head studies.MethodsPatients presenting with moderate to severe intensity migraine without aura were randomized to receive either 400 mg of iVPA or 10 mg intramuscular metoclopramide + 6 mg SQ sumatriptan (30 patients in each study arm). The severity of headache and other associated symptoms such as photophobia and phonophobia were assessed at baseline and after 20 minutes and 1, 2, 4, and 24 hours. The primary end point was to compare the efficacy of the 2 study treatments in relieving headache from moderate-severe to none-mild and of other associated symptoms within a period of 24 hours.ResultsPain relief from severe or moderate to mild or none was obtained in 53.3% of subjects in the iVPA arm and 23.3% in the metoclopramide + sumatriptan arm at 1 hour following treatment (P = .033), whereas 60% and 30% reported pain relief at 2 hour (P = .037). There was no other significant difference in alleviation of associated migraine symptoms between the 2 arms. No serious adverse effects were noted.ConclusionTreatment with iVPA was more effective than metoclopramide + SQ sumatriptan during the first 2 hours in patients with a prolonged migraine.     

Sleep features and central sensitization symptoms in primary headache patients

Background

Association between sleep disorders and headache is largely known. The aim of the present study was to evaluate sleep quality and quantity in a large cohort of primary headache patients, in order to correlate these scores with symptoms of central sensitization as allodynia, pericranial tenderness and comorbidity with diffuse muscle-skeletal pain.

Methods

One thousand six hundreds and seventy primary headache out patients were submitted to the Medical Outcomes Study (MOS) within a clinical assessment, consisting of evaluation of frequency of headache, pericranial tenderness, allodynia and coexistence of fibromyalgia syndrome (FM).

Results

Ten groups of primary headache patients were individuated, including patients with episodic and chronic migraine and tension type headache, mixed forms, cluster headache and other trigeminal autonomic cephalalgias. Duration but not sleep disturbances score was correlated with symptoms of central sensitization as allodynia and pericranial tenderness in primary headache patients. The association among allodynia, pericranial tenderness and short sleep characterized chronic migraine more than any other primary headache form. Patients presenting with FM comorbidity suffered from sleep disturbances in addition to reduction of sleep duration.

Conclusion

Self reported duration of sleep seems a useful index to be correlated with allodynia, pericranial tenderness and chronic headache as a therapeutic target to be assessed in forthcoming studies aiming to prevent central sensitization symptoms development.     

Comparison of tolerability and efficacy of a combination of paracetamol?+?caffeine and sumatriptan in the treatment of migraine attack: a randomized,double-blind,double-dummy,cross-over study

In this study, we compared the efficacy and tolerability of the combination of paracetamol 1,000 mg + caffeine 130 mg (PCF) with sumatriptan 50 mg (SUM) in migraine attacks. This was a multi-center randomized double-blind, double-dummy, cross-over controlled trial. The efficacy was assessed by the sum of pain intensity differences, the curve of mean pain intensity, the number of pain free at 2 h, and the total pain relief. Tolerability was assessed by recording adverse events within 4 h after drug assumption and evaluating the global judgement of patients. The comparison of these parameters did not show differences between the two drugs which resulted absolutely overlapping in pain relief and patients evaluation. In conclusion, we confirm the efficacy and safety of PCF such as SUM in the treatment of migraine attacks.     

Combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine: a multicentre double-blind placebo-controlled study

This multicentre, double-blind, randomized, placebo-controlled, parallel study was designed to evaluate the efficacy of combined oral lysine acetylsalicylate and metoclopramide (LAS-MCP) in the acute treatment of migraine attacks. A total of 266 patients, 18–65 years old, with two to six attacks of migraine with or without aura (IHS criteria) per month were included. The patients had to treat two migraine attacks with LAS-MCP (1620 mg lysine acetylsalicylate-the equivalent of 900 mg aspirin- combined with 10 mg metoclopramide) or placebo. The main outcome measure was headache relief (reduction in headache severity from grade 3 or 2-severe or moderate-to grade 1 or 0-mild or none) 2 h after treatment. LAS-MCP was superior to placebo for headache relief (56% vs 28%) and for the following secondary outcome measures: complete headache relief (18% vs 7%; p < 0.001), nausea (28% vs 44%; p < 0.001), vomiting (3% vs 11%; p = 0.001), use of rescue medication (47% vs 68%; p < 0.001), global efficacy judged as good or excellent (32% vs 14%; p < 0.001). The tolerability was considered as good in 94% of treated attacks in both groups. Combined oral lysine acetylsalicylate and metoclopramide is an effective and well-tolerated acute treatment of migraine attacks.     

Prevention of migraine with olmesartan in patients with hypertension/prehypertension

OBJECTIVE: To explore the effects of olmesartan on frequency and severity of migraine attacks in patients with comorbid hypertension and prehypertension. BACKGROUND: A randomized, double-blind, placebo-controlled, crossover study with a total of 60 patients has demonstrated the efficacy and safety of the angiotensin II receptor blocker candesartan in migraine prophylaxis. We study the potential efficacy and tolerability of olmesartan in preventing migraine in patients with hypertension and prehypertension. DESIGN/METHODS: Twenty-four adults, aged 27 through 76, with either hypertension or prehypertension, were included in this open-label study. Participants suffered from migraines (diagnosed according to International Headache Society classifications) for at least 3 months. Patients were treated with 10 to 40 mg of olmesartan per various observational periods of at least 3 months. Frequency and severity were recorded by office visits or by telephonic interview. RESULTS: Patients reported an 82.5% average reduction in the frequency of migraine attacks. Patients also experienced a 45% average reduction in the severity of migraine attacks measured on a numeric pain scale of 1 to 10. The only undesired effect was dizziness or presyncope. No serious adverse events occurred and no adverse event caused a premature termination. Two patients had no reduction in headache frequency, intensity, and blood pressure. CONCLUSIONS: The favorable results and low rate of adverse effects, in this open migraine prevention study in patients with hypertension or prehypertension, are similar to results of the randomized, double-blind, placebo-controlled, crossover study in patients taking candesartan. Olmesartan shows a potential as an effective and well-tolerated migraine prophylactic agent for patients with comorbid hypertension and prehypertension.     

Intravenous dipyrone in the acute treatment of migraine without aura and migraine with aura: a randomized,double blind,placebo controlled study

BACKGROUND: Dipyrone (Metamizol) has been used in the acute treatment of migraines in Brazil. Some investigators have found it to be a highly effective medication for migraine pain and associated symptoms. OBJECTIVE: To conduct a randomized, placebo controlled, double blind study to assess the effect of dipyrone on the pain and symptoms associated with migraine without aura or with aura and the adverse effect profile of this medication. METHODS: For the migraine without aura group, 44 patients were assigned at random to receive 1 g intravenous dipyrone, and 30 patients received 10 mL 0.9% physiological saline. For the migraine with aura group, 30 patients received both dipyrone or placebo. We used seven parameters of analgesic evaluation and an analog scale to assess nausea, photophobia, and phonophobia. RESULTS: Patients receiving dipyrone demonstrated a statistically superior improvement (P<.05 and P<.01) in pain and all associated symptoms compared with control subjects. CONCLUSIONS: Dipyrone is an effective drug for the relief of acute migraine pain and associated symptoms.     

Rizatriptan 5 mg for the acute treatment of migraine in adolescents: results from a double-blind, single-attack study and two open-label, multiple-attack studies

OBJECTIVE: To examine the short- and long-term efficacy and tolerability of rizatriptan 5 mg in adolescents with migraine. METHODS: Two studies were conducted in patients aged 12 to 17 years. The first study was a randomized, double-blind, placebo-controlled, single-attack study followed by a randomized, 1-year, open-label extension. The second study was a randomized, 1-year, open-label study. In the single-attack study, patients treated a moderate or severe migraine headache and up to two recurrences with rizatriptan 5-mg tablets (n = 234) or placebo (n = 242). Patients were instructed to use the study medication only on nonschool days. Headache severity, associated symptoms, and functional disability were assessed by the patient at 0.5, 1, 1.5, 2, 3, and 4 hours after the initial dose. In the 1-year studies, patients treated up to 6 migraine attacks per month with rizatriptan 5-mg tablets (n = 273), rizatriptan 5-mg wafers (n = 281), or standard care therapy (n = 132). Headache severity was assessed by the patient at 2 hours after the initial dose. In all studies, the primary efficacy measure was pain relief at 2 hours post dose. RESULTS: In the single-attack study, the proportion of patients with pain relief at 2 hours was not significantly different between rizatriptan 5 mg (68.2%) and placebo (68.8%). Fewer patients than expected (about 30%) treated their migraine attacks on the weekend. Among these patients, the proportion with pain relief at 2 hours was significantly higher in the rizatriptan group than in the placebo group (74% vs. 58%, P = 0.022). In the multiple-attack studies, pain relief at 2 hours was achieved in significantly more attacks treated with rizatriptan 5-mg tablet (77%) or with rizatriptan 5-mg wafer (77%) than with standard care (64%). Rizatriptan 5 mg was well tolerated in both the studies, with an adverse event profile not significantly different from that of placebo or standard care. CONCLUSIONS: Rizatriptan 5 mg was not more effective than placebo in the treatment of a single migraine attack in adolescents, but appeared to be more effective than standard care for treating multiple attacks occurring over 1 year in these patients. Rizatriptan 5 mg was well tolerated in adolescents during short-term and long-term use.     

Sumatriptan in Acute Migraine Using a Novel Cartridge System Self-Injector

SYNOPSIS
This double-blind. randomized, placebo-controlled, parallel-group, multicenter study assessed the efficacy, acceptability, safety, and tolerability of subcutaneous sumatriptan 6 mg administered using a novel cartridge system self-injector for the acute treatment of migraine.
Eighty-six patients treated one migraine attack at home with sumatriptan or placebo. A second identical injection was available after 1 hour for inadequate relief or if the headache recurred. Rescue medication was available I hour later. The primary end point was headache relief (improvement in headache from moderate or severe to mild or no pain) within 60 minutes of the first injection. Secondary end points included the acceptability of the self-injector, requirement for and efficacy of a second dose, relief of nonheadache symptoms, use of rescue medication, and adverse events.
Significantly more patients taking sumatriptan than placebo reported headache relief I hour after the first injection (88% vs 11%, P <0.001). The device was well accepted by patients; about 90% found it easy to use and wanted to take further medication using it. Significantly fewer patients taking sumatriptan than placebo required a second injection (33% vs 92%, P <0.001) or rescue medication after the second injection (35% vs 67% P <0.05). Significantly more patients taking sumatriptan than placebo reported headache relief after the second injection (83% vs 32%, P <0.01), and resolution of non-headache migraine symptoms (54% vs 23%, P <0.01). Sumatriptan was generally well tolerated.
Subcutaneous sumatriptan 6 mg self-administered using the novel self-injector is an effective, well accepted, and well tolerated acute treatment of migraine.     

Clinical efficacy of rizatriptan for patients with migraine: efficacy of drug therapy for migraine accompanied by tension headache–like symptoms, focusing on neck stiffness

According to an epidemiological study in Japan, there are as many as 22 million patients with tension headache and 8.4 million with migraine. Furthermore, patients suffering from both types of headache concurrently are estimated to account for more than 50% of headache patients. We studied the efficacy of drug therapy for migraine accompanied by tension headache–like symptoms, focusing principally on neck stiffness. We evaluated the efficacy of rizatriptan by comparison of findings before and after therapy in 34 migraine patients, consisting of 16 without neck stiffness (migraine without neck factor: WONF) and 18 with it (migraine with neck factor: WNF), who received treatment at our neurology/internal medicine department from 1 March 2004 to 31 May 2005. In the study, all the patients were asked to keep a record of their migraine status. The severity of migraine was classified by physicians according to the International Headache Society diagnostic criteria, based on which drug efficacy was evaluated. We selected rizatriptan for migraine treatment in our study based on Dr. Ferrari’s report. In the efficacy study of rizatriptan, in the group of 34 migraine patients, the pain relief rate (79.4%) and pain–free rate (41.2%) at two hours after treatment were as high as those reported in the meta–analysis performed by Ferrari et al., indicating high efficacy of rizatriptan. In the efficacy comparison between the WONF and WNF groups, the painfree rates were 56.3% and 27.8%, and cumulative pain relief rates were 100% and 61.1%, respectively, with better results in the WONF group. A test result was also significantly better (p=0.0076) in the WONF group. Rizatriptan was proved effective in treating migraine patients accompanied by tension headachelike symptoms. Comparison of efficacy rates between patient groups with and without tension headache–like symptoms showed that the pain relief rate in the group without neck stiffness was higher.     

A Sumatriptan Iontophoretic Transdermal System for the Acute Treatment of Migraine

Objective.— Gastrointestinal symptoms, such as nausea and vomiting, occur almost universally at one time or another in patients during a migraine attack. One third of patients who experience migraine‐related nausea report that this symptom interferes with their ability to take oral medications. The sumatriptan iontophoretic transdermal system (NuPathe Inc., Conshohocken, PA, USA) uses proprietary technology to circumvent the gastrointestinal tract while delivering triptan therapy. This phase III randomized, double‐blind, placebo‐controlled trial evaluated the efficacy and tolerability of this system for the acute treatment of migraine. Methods.— Patients were randomized to treat a single moderate‐to‐severe migraine attack with the sumatriptan iontophoretic transdermal system or placebo. The primary end point was the proportion of patients who were headache pain‐free 2 hours after patch activation. Other end points included the proportions of patients who reported headache pain relief, and freedom from nausea, photophobia, and phonophobia; rescue medication use; and tolerability. Results.— Four hundred sixty‐nine patients were treated. Significantly more patients treated with the sumatriptan iontophoretic transdermal system compared with placebo experienced freedom from headache pain, nausea, photophobia, and phonophobia 2 hours after patch activation, experienced rapid and sustained headache pain relief, and used less rescue medication. Treatment‐emergent adverse events were reported by 50% and 44% of patients treated with the sumatriptan iontophoretic transdermal system and placebo, respectively. Most events were transient mild‐to‐moderate application‐site reactions. Conclusions.— The sumatriptan iontophoretic transdermal system is effective and well tolerated, and may be particularly useful in patients with migraine‐related gastrointestinal symptoms such as nausea.     

Duration of effect of botulinum toxin type A in adult patients with cervical dystonia: a retrospective chart review

BACKGROUND: Clinical trials have established the efficacy and safety of botulinum toxin type A (BTX-A) in patients with cervical dystonia. To maintain the clinical benefits of BTX-A, injections need to be repeated whenever patients' symptoms begin to recur. OBJECTIVE: The purpose of this study was to determine, in clinical practice settings, the mean duration of effect of BTX-A in the treatment of adult patients with cervical dystonia. METHODS: A retrospective chart review was undertaken at an academic center and a private neurology practice. At each site, > or =50 patients being treated for cervical dystonia were identified and randomized for chart review. Patients had to have received the first assessable injection of BTX-A between January 1, 1998, and March 31, 1998, to coincide with the clinical availability of the most current formulation of the neurotoxin. A chart was eligible for review if the patient was aged > or =18 years, had a documented diagnosis of idiopathic cervical dystonia, was being treated with BTX-A, and had been under the continuous care of investigators from January 1, 1998, to August 31, 1999. Of the 102 patients initially identified, the first 30 from each site who met the study inclusion criteria were assessed for (1) age and sex; (2) severity of dystonia; (3) years of BTX-A use; (4) dates of first, second, third, and fourth BTX-A injections; (5) drug dose; (6) use of electromyography; (7) use of other prescribed therapies; (8) laboratory tests; and (9) adverse events. The mean interval between each visit and mean per-patient duration of effect were calculated and stratified by patient characteristics. RESULTS: The mean age of the patients was 56.4 years. Two thirds of the patients were women. Forty-one of the 60 patients (68.3%) had either moderate or severe disease, and 48 (80.0%) had experienced cervical dystonia for >5 years. The mean per-patient duration of effect across the 4 visits was 15.5 weeks (range, 12.2-24.3 weeks). The duration of effect did not differ significantly between study sites despite the differences in disease severity, drug dose, and use of adjunctive therapy. CONCLUSION: BTX-A the controls symptoms of cervical dystonia for 12 to 24 weeks, with a mean duration of effect per patient of 15.5 weeks.     

Oral sumatriptan for the acute treatment of probable migraine: first randomized, controlled study

OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan tablets in adults who meet International Headache Society (IHS) criteria for probable migraine but who do not meet IHS criteria for migraine with or without aura. BACKGROUND: Headaches with some but not all of the features of migraine meet criteria for probable migraine, a form of migraine recognized by the IHS. Probable migraine attacks are also prevalent and frequently underdiagnosed. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled, parallel-group study. Adults (18 to 65 years) with a 1-year history of headaches that met 2004 IHS criteria for probable migraine without aura (same operational definition as 1988 IHS migrainous disorder) were eligible for enrollment. All patients were triptan- and ergot-na?ve and had never been diagnosed with migraine. Patients were randomized in a 1:1:1:1 fashion to receive sumatriptan 25, 50, or 100 mg conventional tablets or matching placebo and were instructed to treat a single moderate or severe probable migraine attack. A post hoc analysis was conducted to evaluate the population of patients who achieved headache relief sustained throughout the immediate posttreatment period. Patients who reported relief within 2 hours and subsequently lost headache relief within 4 hours were considered nonresponders. RESULTS: At 2 hours, more patients treated with sumatriptan achieved headache relief, the primary efficacy measure, compared with placebo, but differences only approached statistical significance for 100 mg (P= .053). The 2-hour headache relief rate in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. The time to use of rescue was significantly shorter in the placebo group compared with the sumatriptan 100 mg group (P= .002). The time to use of rescue in the sumatriptan 25 or 50 mg groups was not significantly different than placebo. More patients treated with placebo (22%) lost headache relief within 4 hours compared with patients treated with sumatriptan 25 mg (17%), 50 mg (14%), or 100 mg (7%). A post hoc analysis demonstrated that at 2 hours, headache relief sustained through 4 hours (S 0-4 hours) was achieved in 44%, 49%, and 57% of patients treated with sumatriptan 25, 50, and 100 mg, respectively, compared with 34% of patients treated with placebo (P < .05 for sumatriptan 50 and 100 mg vs. placebo). All doses of sumatriptan were well tolerated and no serious adverse events were reported. CONCLUSION: These results suggest that oral sumatriptan may be effective and is well tolerated for the acute treatment of probable migraine without aura, however, the difference between sumatriptan and placebo was not statistically significant for the a priori defined primary endpoint.     

Meta‐Analysis of the Efficacy and Safety of Naproxen Sodium in the Acute Treatment of Migraine

(Headache 2010;50:808‐818) Objective.— To assess the efficacy and safety of naproxen sodium in the treatment of acute migraine attacks. Background.— Non‐steroidal anti‐inflammatory drugs including naproxen sodium have been used in treating migraine attack. A number of clinical trials of naproxen sodium in migraine have been reported. However, it remains to be established whether naproxen sodium unequivocally offers clinical benefits taken into account the desired outcomes in acute migraine therapy as recommended by the International Headache Society. Methods.— Clinical trials were identified through electronic searches (MEDLINE, EMBASE, EBM review, and the Cochrane Library) up to June 2009 and historical searches of relevant articles. Studies were included in the meta‐analysis if they were (1) double‐blind, randomized, placebo‐controlled trials that evaluated naproxen sodium tablet in moderate or severe migraine attacks in adult patients, and (2) reporting the efficacy in terms of headache relief, pain‐free, relief of migraine‐associated symptoms, sustained headache relief, sustained pain‐free, or headache recurrence. Data extraction and study quality assessment were performed independently by 2 investigators. Disagreements were resolved by a third investigator. Treatment effects and adverse effects were expressed as risk ratio. A random effects model was used when significant heterogeneity existed, otherwise the fixed effects model was performed. Results.— We identified 16 published randomized controlled trials of naproxen in the treatment of migraine. Four trials met the inclusion criteria and were included in the meta‐analysis. Naproxen sodium was more effective than placebo in reducing pain intensity and providing pain‐free within 2 hours in adults with moderate or severe migraine attacks. The pooled risk ratios were 1.58 (95% confidence interval [CI] 1.41‐1.77, P < .00001), and 2.22 (95% CI 1.46‐3.37, P = .0002), respectively, for headache relief at 2 hours and pain‐free at 2 hours. It was also effective in achieving headache relief at 4 hours, relief of migraine‐associated symptoms, sustained headache relief, and sustained pain‐free responses. There was no significant difference in headache recurrence rate between naproxen sodium and placebo. The risk of any adverse event was greater with naproxen sodium than with placebo (pooled risk ratio 1.29, 95% CI 1.04‐1.60, P = .02). The adverse events commonly associated with naproxen sodium were nausea, dizziness, dyspepsia, and abdominal pain. Conclusions.— The available evidence suggests that naproxen sodium is more effective but may cause more adverse events than placebo in the acute treatment of moderate to severe migraine. It is effective in reducing headache intensity, rendering pain‐free at 2 hours and improving migraine‐associated symptoms. However, its effectiveness relative to other active comparators needs to be better defined by appropriate head‐to‐head clinical trials.