• Prescrire Int. 2004 Feb 1;13(69):22-5.

Abstract(1) The first-line drugs for mild to moderate pain are non opiate analgesics, namely paracetamol and nonsteroidal antiinflammatory drugs (NSAIDs). (2) Codeine, dextropropoxyphene and tramadol are weak opiates; they are often used with paracetamol in fixed-dose combinations, in order to reinforce the analgesic effect of paracetamol. (3) These analgesic combinations have only been evaluated in a few situations associated with chronic and acute pain. And the endpoints used in clinical trials are designed more to show statistically significant differences than clear clinical differences. (4) In acute pain, available meta-analyses confirm that the first-line drug is paracetamol, or, if necessary, ibuprofen, a NSAID. (5) The paracetamol + codeine combination slightly increases the analgesic effect of paracetamol, but causes more adverse effects. Combinations of paracetamol + dextropropoxyphene and paracetamol + tramadol are even less useful. (6) The few available clinical trials fail to demonstrate that combining paracetamol with a NSAID is any more effective than either drug given alone, while adverse effects are increased. (7) Paracetamol is also the first-line treatment for chronic non cancer pain, such as low back pain or pain due to osteoarthritis of the hip. NSAIDs have no advantages over paracetamol in these settings. We found no trials of paracetamol + NSAID combinations. Combinations of paracetamol and weak opiates have been inadequately studied in this situation, and are only second-line options.

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