Search

The efficacy of acute therapies for migraine can be measured in many ways. Traditional endpoints (such as reduction in pain from moderate or severe to mild or absent) are used for regulatory purposes, but do not reflect all components of the migraine syndrome, nor, necessarily, what is most valued by patients and clinicians. There is also a pharmacokinetic-pharmacodynamic disconnection for these traditional types of endpoint, suggesting that they teach us little about how these drugs work. More rigorous, but nonetheless pain-score based, endpoints are reviewed. The biases that can attach to measures such as therapeutic gain and number needed to treat, in the context of migraine therapy, and the limitations of these measures for use in meta-analysis, are discussed. The clinical subtleties of these endpoints are numerous: understanding patients' ability to distinguish between multiple headache types, the best timing of treatment relative to the start of an attack, and measuring clinical outcome may be statistically difficult, but yet may also provide more clinical utility than pain-score analyses. The three therapeutic strategies (Step, Stepped-within-attack, and Stratified care) are reviewed and the place of 5HT[sub 1B/1D] agonists within them, based on the currently best available evidence, is identified. Consideration should be given to more real-life studies, to measuring drug efficacy after early administration during onset of headache, and to greater sophistication in our approach to the necessarily gestalt measures of patient satisfaction and treatment preference. [ABSTRACT FROM AUTHOR]

The article provides an overview of opioid chronopharmacology. Several traditional activities of analgesic opioids include non-opioid receptor interactions and pharmaceutical convenience. It describes the mechanism of actions of buprenorphine, remifentanil and levo-alpha-acetyl methadol. The article concludes that chronopharmacology influence the proper therapeutic uses of opioids and their popularity for abuse.