Biomedical subjects

Paul K Winner

Publications and source records attributed to Paul K Winner.

4 recordsLinked to original sources

PubMed2005

Pediatric migraine: recognition and treatment.

The diagnosis of migraine headache in childhood rests on criteria similar to those used in migraine in adults. It is important, however, to appreciate several fundamental differences. These differences include the duration of attack, which is often far shorter than in an adult, and the location of the attack, which may be bilateral in many children. The treatment of children and adolescents with migraines includes treatment modalities for acute attacks, preventive medications when the attacks are frequent, and biobehavioral modes of therapy to address long-term management of the disorder. The controlled clinical trials of medications in pediatric migraine have suffered from high placebo response rates that may be related to the sites conducting the study (ie, headache specialist vs clinical research organizations). The medications have proved to be safe in the pediatric age group. Treatment modalities for acute migraine include over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), as well as the oral triptans such as sumatriptan succinate, rizatriptan benzoate, and zolmitriptan and the nasal spray formulations of sumatriptan and zolmitriptan. Subcutaneous sumatriptan and parenteral dihydroergotamine have also been used limitedly. Preventive treatment for patients with frequent or disabling migraines (or both) includes the antidepressants amitriptyline hydrochloride and nortriptyline hydrochloride, the anticonvulsants divalproex sodium and topiramate, and the antihistaminic agent cyprohepatine hydrochloride. Biobehavioral approaches aimed at addressing the fundamental lifestyle issues and nonpharmacologic approaches to management are fundamental to long-term success.

Analgesics↗

PubMed2003

Migraine preventive medication reduces resource utilization.

OBJECTIVE: To determine if long-term resource utilization is reduced by adding a preventive medication to a migraine management regimen that already includes acute medication. BACKGROUND: In 2000, new evidence-based guidelines for the treatment of migraine were released by the US Headache Consortium and the American Academy of Neurology. Although these guidelines emphasize the role of preventive medication in achieving significant clinical improvement, little yet is known concerning the impact of such management on medical and pharmaceutical resources. Methods.-Resource utilization information in a large claims database was analyzed retrospectively. RESULTS: Adding a preventive medication to migraine management reduced the use of other migraine medications, as well as visits to physician offices and emergency departments. In addition, both acute and preventive medications were associated with lower utilization of computed tomography and magnetic resonance imaging scans. CONCLUSION: Migraine preventive drug therapy is effective in reducing resource consumption when added to therapy consisting only of an acute medication.

Amitriptyline↗

PubMed2002

Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled, multicenter outcome study.

OBJECTIVE: To assess the efficacy of tizanidine hydrochloride versus placebo as adjunctive prophylactic therapy for chronic daily headache (chronic migraine, migrainous headache, or tension-type headache). BACKGROUND: Tizanidine is an alpha2-adrenergic agonist that inhibits the release of norepinephrine at both the spinal cord and brain, with antinociceptive effects that are independent of the endogenous opioid system. Previous open-label studies have suggested the drug may be effective for treatment of chronic daily headache. METHODS: Two hundred patients completed a 4-week, single-blind, placebo baseline period, with 134 fulfilling selection criteria and then randomized to tizanidine or placebo. Ninety-two patients completed at least 8 weeks of treatment (tizanidine, n = 45; placebo, n = 47), and 85 patients completed 12 weeks of treatment (tizanidine, n = 44; placebo, n = 41). Most patients (77%) met the diagnostic criteria for migraine of the International Headache Society; 23% had either chronic migrainous headache or chronic tension-type headache. Tizanidine was slowly titrated over 4 weeks to 24 mg or the maximum dose tolerated (mean, 18 mg; SD, 6.4; median, 20.0; range, 2 to 24), divided equally over three dose intervals per day. Overall headache index ([headache days x average intensity x duration in hours]/28 days) was the primary end point. RESULTS: Tizanidine was shown to be superior to placebo in reducing the overall headache index (P =.0025), as well as mean headache days per week (P =.0193), severe headache days per week (P =.0211), average headache intensity (P =.0108), peak headache intensity (P =.0020), and mean headache duration (P =.0127). The mean percentage improvement during the last 4 weeks of treatment with tizanidine versus placebo was 54% versus 19% for the headache index (P =.0144), 55% versus 21% for severe headache days (P =.0331), 35% versus 19% for headache duration (P =.0142), 35% versus 20% for peak headache intensity (P =.0106), 33% versus 20% for average headache intensity (P =.0281), and 30% versus 22% for total headache days (P =.0593). Patients receiving tizanidine also scored higher ratings of overall headache improvement on a visual analog scale (P =.0069). There was no statistically significant difference in outcome for patients with chronic migraine versus those with only migrainous or tension-type headache. Adverse effects reported by more than 10% of the patients included somnolence (47%), dizziness (24%), dry mouth (23%), and asthenia (19%). Dropouts due to adverse events did not differ significantly between tizanidine and placebo. CONCLUSIONS: The results support tizanidine as an effective prophylactic adjunct for chronic daily headache, including migraine, migrainous headache, and tension-type headache. These results also suggest the possible importance of an alpha2-adrenergic mechanism underlying the pathophysiology of this spectrum of headache disorders.

Adolescent↗

PubMed2002

GW320659 for the treatment of attention-deficit/hyperactivity disorder in children.

OBJECTIVE: To assess the safety, tolerability, and efficacy of GW320659, a chemically novel inhibitor of norepinephrine and dopamine reuptake, in pediatric attention-deficit/hyperactivity disorder (ADHD). METHOD: This was a multicenter, open-label, dose-titration study of seven daily dose levels of GW320659: 1.25, 2.5, 5, 7.5,10,12.5, and 15 mg. Treatment began with the lowest dose of GW320659 and increased weekly until subjects (mean age 9.1 years) achieved a maximum acceptable dose. Subjects remained at their maximum acceptable dose for a 4-week treatment period. The key efficacy end-point was clinical response (Clinical Global Impressions of Improvement score of 1 or 2 and an improvement of 5 or more points on at least one of the Conners Parent or Teacher Rating Scales Tscore). Other end-points included assessments of safety and of quality of life using the Child Health Questionnaire Parent Form 28 (CHQ-PF28). RESULTS: Fifty-one subjects entered the titration phase and 46 subjects completed the study. During the treatment phase, these 46 subjects received a mean dose of 14.2 mg/day and the maximum exposure to GW320659 was 11 weeks. At the end of the treatment period, 76% of subjects showed improvement with GW320659 and there were significant improvements in 7 of the 12 subscales of the CHQ-PF28 compared with baseline (p < .05). Adverse events were generally mild; only five subjects required downward titration because of adverse events (three psychiatric, one neurological and urological, one cardiovascular), and no subject withdrew because of adverse events. CONCLUSIONS: GW320659 may have clinically relevant efficacy in pediatric ADHD and was well tolerated in this short-term initial study in children.

Adrenergic Uptake Inhibitors↗