Biomedical subjects

Andrew J Dowson

Publications and source records attributed to Andrew J Dowson.

6 recordsLinked to original sources

PubMed2003

Analysis of the patients attending a specialist UK headache clinic over a 3-year period.

OBJECTIVE: This study analyzed the profile of patients who attended a specialist UK headache clinic over a 3-year period. METHODS: An audit was conducted of the clinical records of patients attending the specialist headache clinic at King's College, London, between January 1997 and January 2000. Data were collected for diagnoses given, current medications taken, medications prescribed and recommended, and investigations conducted. Results were calculated as numbers and proportions of patients for the 3-year period and for the 3 separate 12-month periods. RESULTS: A total of 458 patients were included in the audit. Most patients were diagnosed as having chronic daily headache (CDH, 60%) or migraine (33%). Prior to the clinic visit, most patients with CDH and migraine treated their headaches with analgesics, and there was little use of prophylactic medication. In the clinic, 74% of patients with CDH and 85% of migraineurs were prescribed prophylactic medication, and 81% of migraineurs were given triptans for acute treatment. Diagnostic testing was performed in 12% of the patients, and all results were normal or negative. CONCLUSIONS: CDH and migraine were the most common headache types encountered in this UK secondary-care clinic. Review of treatment patterns used prior to the initial clinic evaluation suggests that management of CDH and migraine in UK primary care is suboptimal, and educational initiatives are needed to improve headache management.

Analgesics↗

PubMed2003

Speed of onset and efficacy of zolmitriptan nasal spray in the acute treatment of migraine: a randomised, double-blind, placebo-controlled, dose-ranging study versus zolmitriptan tablet.

OBJECTIVE: Zolmitriptan oral tablet is highly effective and well tolerated in the acute treatment of migraine with and without aura in adults. A nasal spray formulation has now been developed. The objective of this study was to compare the efficacy and tolerability of fixed doses of zolmitriptan administered via a nasal spray with placebo and zolmitriptan oral tablet in the acute treatment of migraine. PATIENTS AND STUDY DESIGN: This was a randomised, double-blind, double-dummy, placebo-controlled, parallel-group, multicentre, dose-ranging study. 1547 patients aged 18-65 years with an established diagnosis of migraine with or without aura (as defined by International Headache Society criteria) who had at least a 1-year history of migraine and an age of onset <50 years were included. Patients were able to distinguish typical migraine from nonmigraine headaches and had experienced an average of one to six migraine headaches per month during the 2 months preceding the study. Patients were randomised to zolmitriptan (Zomig) The use of tradenames is for product identification purposes only and does not imply endorsement.) nasal spray (5.0, 2.5, 1.0 or 0.5 mg), zolmitriptan oral tablet (2.5mg) or placebo for the treatment of three moderate or severe migraine attacks. The primary outcome measure was headache response at 2 hours following treatment, defined as reduced intensity of migraine pain (using a scale of none, mild, moderate or severe) from severe or moderate at baseline to mild or no pain at 2 hours after treatment. Secondary outcome measures included early headache response at 15, 30 and 45 minutes and headache response at 1 and 4 hours postdose, as well as pain-free rates at 15, 30 and 45 minutes and 1, 2 and 4 hours postdose. Laboratory assessments, vital signs, 12-lead ECGs and nose and throat examinations were performed at screening and follow-up visits. Adverse events were recorded throughout the study using Coding Symbols for Thesaurus of Adverse Reaction Terms (COSTART) terminology. RESULTS: Each dose of zolmitriptan nasal spray produced a greater 2-hour headache response rate than placebo (70.3%, 58.6%, 54.8% and 41.5% for zolmitriptan nasal spray 5.0, 2.5, 1.0 and 0.5mg, compared with 30.6% for placebo [all p < 0.001 vs placebo]). The 2-hour headache response rate for zolmitriptan nasal spray 5.0mg was significantly higher than that of the zolmitriptan 2.5mg oral tablet (61.3%; p < 0.05), while comparisons of nasal spray 0.5, 1.0 and 2.5mg with zolmitriptan 2.5mg oral tablet were not statistically significant. The nasal spray 5.0 and 2.5mg showed a rapid onset of action, with a significant difference in headache response compared with placebo from 15 minutes through 4 hours after administration and a significant difference between the nasal spray 5.0mg and 2.5mg oral tablet from 15 minutes through to 2 hours (the other nasal spray doses were not statistically significant compared with 2.5mg oral tablet). Zolmitriptan nasal spray resulted in pain-free rates that were dose dependent. While all doses from 1.0 mg upwards produced significant pain-free outcomes from 30 minutes versus placebo, only the 5.0mg dose produced pain-free rates significantly superior to both placebo and the 2.5mg oral tablet. Zolmitriptan nasal spray was well tolerated, with the most common adverse events being unusual taste and paresthesia. The majority of adverse events were of short duration and mild or moderate intensity. Only ten patients were withdrawn from the trial because of adverse events. Serious adverse events were reported by nine patients after taking study medication, but none was considered to be causally related to study medication. Zolmitriptan was not associated with any clinically significant changes in laboratory test values or vital signs. CONCLUSION: All doses of zolmitriptan nasal spray produced significant 2-hour headache response rates compared with placebo. The 5.0 and 2.5mg doses were also significantly more effective than placebo for the majority of secondary efficacy measures. Zolmitriptan nasal spray 5.0mg provided a headache response statistically superior to both placebo and the 2.5mg tablet as early as 15 minutes after administration, while demonstrating pain-free outcomes significantly superior to placebo and the 2.5mg tablet as early as 30 minutes after administration. All doses of zolmitriptan nasal spray were well tolerated, resulting in an optimal therapeutic index and clinical recommendation for the 5.0mg dose.

Administration, Intranasal↗

PubMed2003

Tolerability and consistency of effect of zolmitriptan nasal spray in a long-term migraine treatment trial.

OBJECTIVES: To primarily assess the tolerability of zolmitriptan (Zomig) nasal spray 5mg in the long-term treatment of migraine, as well as determine efficacy and consistency of effect over time (up to 1 year). METHODS: This randomised, double-blind-to-dose, parallel-group, multicentre study was designed as a two-phase, crossover trial with a total duration of 1 year. In the pre-crossover phase, 1,093 patients aged 18-65 years with an established diagnosis of migraine with or without aura received intranasal zolmitriptan 5, 2.5, 1 or 0.5mg for the treatment of mild, moderate or severe migraine attacks. When a headache persisted or recurred, a second dose of zolmitriptan nasal spray (or other approved escape medication) was permitted 2 hours post-administration but no later than 24 hours after the first dose. In the post-crossover phase, once a placebo-controlled, dose-finding study had established 5mg as the dose with the optimal clinical utility, all patients were crossed over under blinded conditions to receive this dose. As this was primarily a safety study, the primary endpoints for the study were the incidence and nature of all serious adverse events (at any time before or after administration) and nonserious adverse events (within 24 hours of administration), as well as the incidence of clinically significant abnormalities in either ECG or haematology and clinical chemistry parameters. Nose and throat examinations were performed before and after the study at 30 predetermined trial centres. Other endpoint measures included headache response rate, pain-free assessments, reduction in headache intensity, time to resumption of normal activities and consistency of headache response. Efficacy rates were measured in 90-day intervals up to a period of 360 days. RESULTS: Zolmitriptan nasal spray 5mg was well tolerated, with only 1.9% of patients withdrawing from the 12-month long-term trial because of adverse events. Adverse events occurred in 22.1% of attacks treated with zolmitriptan nasal spray 5mg, and the majority were of short duration and mild or moderate intensity. Serious adverse events occurred in 0.2% of attacks treated with zolmitriptan nasal spray 5mg. There was no evidence of increased incidence of adverse events with increasing duration of treatment. Nasopharyngeal adverse events were reported in 5.5% of attacks treated with zolmitriptan nasal spray 5mg. Again, events were generally transient and of mild intensity. For the 1,093 patients who treated 13,806 attacks during the pre-crossover phase, headache response rates at 2 hours over all attacks were 73.2%, 70.5%, 49.9% and 41.5% for zolmitriptan nasal spray 5, 2.5, 1 and 0.5mg, respectively. Pain-free rates at 2 hours over all attacks were 51.5%, 48.1%, 24.7% and 21.8%, respectively. For the 783 patients receiving the 5mg dose in either the pre- or post-crossover phases, the 2-hour headache response rates were 72.9%, 74.4%, 74.6% and 74.1% for the four 90-day periods between day 0 and day 360. Normal activities were resumed within 2 hours in 60.4% of attacks. Long-term usage of zolmitriptan nasal spray 5mg was also associated with a consistently effective response, with 57.8% of patients experiencing a 2-hour headache response in over 75% of attacks. The majority of patients (70.3%) rated their overall satisfaction with zolmitriptan nasal spray 5mg as good or excellent. CONCLUSION: Zolmitriptan nasal spray 5mg provides good tolerability and efficacy in long-term use in a clinical setting, with consistently high 2-hour headache and pain-free rates. This combination of benefits translates to high patient satisfaction with this formulation of zolmitriptan.

Administration, Intranasal↗

PubMed2003

Casebook: headache.

Headache alone rarely indicates a sinister underlying cause. However, if the red flags are flying -- that is, if the patient is over 30 years old when the first headache develops, has additional symptoms or signs or has a very acute onset, particularly involving vomiting, then suspicion should be raised (see table 4). Although migraine has a high impact on the sufferer and affects a large proportion of the population on a monthly basis, the problem of acute muscle contraction headache is far greater. Other forms of headache are actually uncommon in comparison to these two. However, chronic daily headache is the most common condition seen by the medical professional because of its impact on the patient's quality of life. The key to the management of this condition is the assessment of analgesic dependence including NSAIDs, and particularly the codeine-containing agents. These should be avoided while long-term aproached such as exercise and certain prophylactic agents are introduced. It is true to say that if a careful initial assessment is made leading to a correct diagnosis, then the chance of appropriate management is enormously increased. Patients undergoing the correct management should generally see a massive improvement in their quality of life. Headache can, therefore, be a very satisfying condition for the clinician to treat.

Adult↗

PubMed2002

How does almotriptan compare with other triptans? A review of data from placebo-controlled clinical trials.

Almotriptan, the new selective 5-HT1B/1D agonist, has a higher oral bioavailability than any other triptan, with more than two thirds of the administered dose absorbed within the first hour both inside and outside of a migraine attack. Gender or the presence of food in the stomach does not affect its pharmacokinetic profile, and the compound has no clinically relevant interactions with other drugs. Among the available triptans, response rates at 2 hours range from 50% to 80%, with 20% to 50% of patients pain-free. Almotriptan 12.5 mg provides similar efficacy, with significant advantage over placebo at 30 minutes and a reliable consistency (75% in two of three attacks). Headache typically recurs in 25% to 45% of patients with most triptans. The recurrence rate with almotriptan 12.5 mg, 18% to 27%, is among the lowest reported. The tolerability of almotriptan 12.5 mg is close to that of placebo with a low incidence of central nervous system side effects and chest symptoms. In conclusion, almotriptan's consistent pharmacokinetics and good efficacy, in combination with excellent tolerability, make it an attractive choice in the acute treatment of migraine attacks.

Humans↗

PubMed2002

Review of zolmitriptan and its clinical applications in migraine.

Preclinical studies have shown that zolmitriptan is a selective serotonin 5-HT(1B/1D) receptor agonist (triptan). Randomised, placebo-controlled, double-blind trials in patients with migraine have shown that zolmitriptan has good efficacy measured using 2 h response and pain-free rates. Migraine-associated symptoms, including nausea, photophobia and phonophobia, are also improved with zolmitriptan. Oral zolmitriptan (2.5 and 5 mg) has an onset of action within 45 min and efficacy is sustained in most patients who respond at 2 h. The orally-disintegrating zolmitriptan tablet has the advantage that it may be taken immediately, without the need for additional fluids, any time a migraine headache occurs. Patients may benefit in terms of improved efficacy from the convenience of the disintegrating tablet, since there is evidence that taking triptan therapy as early as possible in an attack is advantageous. For similar reasons, as well as improved efficacy, a nasal spray formulation is in development. Zolmitriptan is effective in the treatment of migraine associated with menses and migraine with aura. There is no tachyphylaxis following repeated doses for multiple attacks of migraine over a prolonged period of time. Compared to placebo, the incidence of persistent migraine headache is reduced by zolmitriptan and recurrent migraine headache occurs less frequently. Zolmitriptan has also shown efficacy in the treatment of persistent and/or recurrent migraine headache. Comparative clinical studies have shown overall that zolmitriptan has similar or superior efficacy to sumatriptan in the treatment of migraine. Specifically, zolmitriptan 2.5 mg was significantly more effective than sumatriptan 25 or 50 mg according to a number of end points, including headache response at 2 h. Oral zolmitriptan is also effective in the acute treatment of cluster headache. Zolmitriptan is generally well tolerated, with most adverse events being mild-to-moderate, transient and resolving without intervention or the need for treatment withdrawal. The consistent efficacy in treating all types of migraine and the choice of available formulations make zolmitriptan acceptable to patients and a suitable first-line therapy for the treatment of migraine.

Administration, Oral↗