Analgesics with barbiturates such as Butalbital are banned in Germany, and expert advisory panels elsewhere have warned of their potential for abuse. Some experts warn that butalbital is particularly likely to lead to rebound (analgesic overuse) headache and/or dependence and question whether their benefit outweighs these problems.

"Butalbital-containing analgesics may be effective as backup medications or when other medications are ineffective or cannot be used. Because of concerns about overuse, medication-overuse headache, and withdrawal, their use should be limited and carefully monitored."

Duke University researched completed clinical studies to identify and summarize evidence on the efficacy and safety of butalbital-containing combination drugs at the request of the United States Headache Consortium. This was as a supplement to the Agency for Health Care Research and Quality-sponsored technical report on the treatment of acute Migraine. The US Headache Consortium is composed of seven member organizations with an interest in improving the quality of care for people with Migraine disorders. The organizations include the American Academy of Neurology (AAN), the American Headache Society (AHS), the American Academy of Family Physicians (AAFP), the American College of Emergency Physicians (ACEP), American College of Physicians-American Society of Internal Medicine (ACP_ASIM), the American Osteopathic Association (AOA) and the National Headache Foundation (NHF).

Their research located controlled trials of Fiorinal, Fiorinal-PA, Fioricet, Fiorinal with Codeine, and Optalidon. Optalidon contains nonsteroidal anti-inflammatory agents (aminophenazone or propyphenazone) not available in the United States. In the located studies, these butalbital-containing compounds were compared with placebo, Micrainin (meprobamate and aspirin), Tylenol #3 (acetaminophen and codeine), Stadol (butorphanol tartrate nasal spray), and aspirin.

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