Fixed Drug Combinations for the Acute Treatment of Migraine

Abstract

Fixed drug combinations (FDCs) combine standardised doses of two or more drugs in a single tablet, injection, nasal spray or suppository. FDCs may improve treatment compliance, efficacy or tolerability through a variety of mechanisms. At present, FDCs are commonly used in migraine treatment, and more are in development. This systematic review identified 43 prospective trials of FDCs in use for the acute treatment of migraine. Quantitative combination and analysis of the data were not possible, but results of the review support the following qualitative conclusions. First, many FDCs in use for the acute treatment of migraine are older drugs. In these cases, clinical trial evidence that the FDC is efficacious or has important advantages over its treatment components is lacking. The benefits assumed for some common FDC ingredients such as caffeine and metoclopramide are not clearly confirmed in these trials. Secondly, the use of barbiturate-containing FDCs for the acute treatment of migraine is not evidence based, and these drugs are frequently implicated in the development of dependence or medication-induced headache syndromes. Thirdly, studied opioid-containing FDCs are generally superior to placebo, but evidence regarding the safety and tolerability of their repeated use in the treatment of migraine is lacking; clinical experience dictates caution in the use of these agents. Fourthly, ergotamine-containing FDCs are generally superior to placebo, but perform poorly in comparison with single-agent selective serotonin 5-HT(1B/1D) receptor agonists ('triptans'), NSAIDs or even isometheptene or opioid comparators, and are less well tolerated. Fifthly, the most consistent and impressive evidence of benefit is for NSAID-containing FDCs. These invariably outperform placebo and are equivalent or superior to active comparators. Finally, with renewed interest in the use of FDCs for the acute treatment of migraine, high-quality evidence of a benefit for such treatments is emerging. An FDC containing a triptan and NSAID seems most likely to provide efficacy and tolerability benefits in the acute treatment of migraine. Such an FDC is in development but not yet approved for use.