The development of new analgesics over the past 50 years: a lack of real breakthrough drugs.

Fifty-nine drugs identified as analgesics were introduced from 1960 to 2009 and remain in use. Seven can be regarded as having novel molecular targets; however, only one, sumatriptan, was sufficiently effective to motivate the introduction of many similar drugs acting at the same target (triptans). Publication productivity in the area of pain grew exponentially during this period. Pain-related publications on morphine were dominant among other analgesics. Very intensive research efforts directed at diverse molecular targets related to pain mechanisms produced thousands of publications, but those efforts have not yet yielded new analgesics with sufficient effectiveness to change the share of publications on opioids or nonsteroidal antiinflammatory drugs. Morphine and aspirin, introduced for the treatment of pain more than a century ago, continue to dominate biomedical publications despite their limited effectiveness in many areas (e.g., neuropathic pain) and multiple serious adverse effects. The present assessment reveals the lack of real breakthroughs in analgesic drug development despite intense research efforts. Possible factors contributing to the apparent drought of novel analgesics are discussed.