Comparative efficacy and safety of inhaled corticosteroids in asthma.

Current guidelines emphasize the efficacy of inhaled corticosteroids for anti-inflammatory activity in asthma, and recommend higher doses and earlier initiation of therapy than previous guidelines. Concern over possible side effects with long term use has prompted an evaluation of the available literature to determine the optimal dose that may be administered without fear that significant side effects might occur (e.g., growth retardation in children, adrenal suppression, reduction in bone mineral density, cataract formation). Regular treatment with the following drugs in adults and children, respectively, is unlikely to result in any clinically significant effects on the above parameters: beclomethasone dipropionate less than 1500 micrograms and 400 micrograms, budesonide less than 1600 micrograms and 400 micrograms, flunisolide less than 2000 micrograms and 1000 micrograms, fluticasone propionate approximately 500 micrograms and 200 micrograms, and triamcinolone acetonide less than 1600 micrograms and 1200 micrograms. Systemic effects are influenced by potency and bioavailability. Inhaled corticosteroids owe their favourable safety profile to a high topical to systemic potency ratio compared with that of oral corticosteroids. In terms of relative topical potency, fluticasone propionate is more potent than budesonide, which is more potent than beclomethasone dipropionate, which is more potent than flunisolide and triamcinolone acetonide. The delivery device has an important influence on the amount of drug reaching the patient. A spacer device attached to a metered dose inhaler or a Turbuhaler reduces oropharyngeal deposition and increases lung deposition. As a result, a dosage reduction may be possible, and local side effects of dysphonia and oral candidiasis may be reduced. Patients requiring continued high doses by the inhaled route should be monitored for systemic effects and be considered for osteoporosis prevention therapy if appropriate.

A systematic review of the use of triptans in acute migraine.

OBJECTIVE: A systematic review of the literature was undertaken, to consolidate evidence concerning the efficacy and safety of triptans currently available in Canada (sumatriptan, rizatriptan, naratriptan, zolmitriptan), and to provide guidelines for selection of a triptan. METHODS: Data from published, randomized, placebo-controlled trials were pooled and a combined number needed to treat (NNT) and number needed to harm (NNH) was generated for each triptan. Direct comparative trials of triptans were also examined. RESULTS: The lowest NNT for headache response/pain-free at one/two hours is observed with subcutaneous sumatriptan. Among the oral formulations, the lowest NNT is observed with rizatriptan and the highest NNT with naratriptan. The lowest NNH is observed with subcutaneous sumatriptan. CONCLUSIONS: Triptans are relatively safe and effective medications for acute migraine attacks. However, differences among them are relatively small. Considerations in selecting a triptan include individual patient response/tolerance, characteristics of the attacks, relief of associated symptoms, consistency of response, headache recurrence, delivery systems and patient preference.

Delivery systems for acute migraine medications.

OBJECTIVE: To discuss advantages and disadvantages of various routes of administration and delivery systems for acute migraine medications, and to assist family physicians in optimizing treatment for individual patients. QUALITY OF EVIDENCE: A MEDLINE search from January 1966 to October 2000 and a Current Contents search for the year 1999 to October 2000 were conducted. Randomized controlled trials were selected, when available. Also included are guidelines (Canadian), non-blinded trials, systematic reviews, and population-based studies. MAIN MESSAGE: Selecting an appropriate way to deliver medication is important in acute migraine therapy. The parenteral route has advantages, such as rapid onset, greater efficacy, and the possibility of use during nausea and vomiting. Disadvantages include local site discomfort, inconvenience, and patients' dislike of needles. Most patients prefer oral therapy, but gastric stasis and nausea and vomiting during a migraine attack might limit its use. The intranasal route usually provides fairly rapid onset, but side effects, such as disturbances in taste, can occur. The rectal route is another option, but absorption is sometimes erratic, rectal irritation can occur, and few migraine medications are available in rectal formulation. CONCLUSION: Selection of appropriate medications and suitable delivery systems for individual patients, based on the characteristics of their attacks (e.g., severity, speed of progression to severe intensity, degree of associated symptoms), ease of administration, and patient preference, will optimize therapy for acute migraine attacks.

Guidelines for the diagnosis and management of migraine in clinical practice. Canadian Headache Society.

OBJECTIVE: To provide physicians and allied health care professionals with guidelines for the diagnosis and management of migraine in clinical practice. OPTIONS: The full range and quality of diagnostic and therapeutic methods available for the management of migraine. OUTCOMES: Improvement in the diagnosis and treatment of migraine, which will lead to a reduction in suffering, increased productivity and decreased economic burden. EVIDENCE AND VALUES: The creation of the guidelines followed a needs assessment by members of the Canadian Headache Society and included a statement of objectives; development of guidelines by multidisciplinary working groups using information from literature reviews and other resources; comparison of alternative clinical pathways and description of how published data were analysed; definition of the level of evidence for data in each case; evaluation and revision of the guidelines at a consensus conference held in Ottawa on Oct. 27-29, 1995; redrafting and insertion of tables showing key variables and data from various studies and tables of data with recommendations; and reassessment by all conference participants. BENEFITS, HARMS AND COSTS: Accuracy in diagnosis is a major factor in improving therapeutic effectiveness. Improvement in the precise diagnosis of migraine, coupled with a rational plan for the treatment of acute attacks and for prophylactic therapy, is likely to lead to substantial benefits in both human and economic terms. RECOMMENDATIONS: The diagnosis of migraine can be improved by using modified criteria of the International Headache Society as well as a semistructured patient interview technique. Appropriate treatment of symptoms should take into account the severity of the migraine attack, since most patients will have attacks of differing severity and can learn to use medication appropriate for each attack. When headaches are frequent or particularly severe, prophylactic therapy should be considered. Both the avoidance of migraine trigger factors and the application of nonpharmacological therapies play important roles in overall migraine management and will be addressed at a later date. VALIDATION: The guidelines are based on consensus of Canadian experts in neurology, emergency medicine, psychiatry, psychology, family medicine and pharmacology, and consumers. Previous guidelines did not exist. Field testing of the guidelines is in progress.

Guidelines for the nonpharmacologic management of migraine in clinical practice. Canadian Headache Society.

OBJECTIVE: To provide physicians and allied health care professionals with guidelines for the nonpharmacologic management of migraine in clinical practice. OPTIONS: The full range and quality of nonpharmacologic therapies available for the management of migraine. OUTCOMES: Improvement in the nonpharmacologic management of migraine. EVIDENCE AND VALUES: The creation of the guidelines followed a needs assessment by members of the Canadian Headache Society and included a statement of objectives; development of guidelines by multidisciplinary working groups using information from literature reviews and other resources; comparison of alternative clinical pathways and description of how published data were analysed; definition of the level of evidence for data in each case; evaluation and revision of the guidelines at a consensus conference held in Ottawa on Oct. 27-29, 1995; redrafting and insertion of tables showing key variables and data from various studies and tables of data with recommendations; and reassessment by all conference participants. BENEFITS, HARMS AND COSTS: Augmentation of the use of nonpharmacologic therapies for the acute and prophylactic management of migraine is likely to lead to substantial benefits in both human and economic terms. RECOMMENDATIONS: Both the avoidance of migraine trigger factors and the use of nonpharmacologic therapies have a part to play in overall migraine management. VALIDATION: The guidelines are based on consensus of Canadian experts in neurology, emergency medicine, psychiatry, psychology and family medicine, and consumers. Previous guidelines did not exist. Field testing of the guidelines is in progress.