Clinical trial of pentazocine in rheumatoid arthritis. Observations on the value of potent analgesics and placebos.

Severe and chronic pain is a dominant feature in most patients with rheumatoid arthritis. Despite optimum doses of standard analgesic and anti-inflammatory drugs, there are many patients who do not obtain adequate pain relief. Until recently, the use of strong analgesics has been strongly contraindicated, as all such available drugs were classified under the Dangerous Drugs Act (DUdley Hart, 1968). The risk of drug dependence in patients with a chronic disease such as rheumatoid arthritis clearly precludes the use of such drugs except in exceptional circumstances. The development of a new group of narcotic antagonists with a benzomorphan nucleus (Archer, Albertson, Harris, Pierson, Bird, Keats, Telford, and Papadopoulos, 1962) led to the introduction of pentazocine in 1967. When given by intramuscular or subcutaneous injection, 30 mg. pentazocine is approximately equinanalgesic with 10 mg. morphine (British Medical Journal, Today's Drugs, 1970). The W.H. O. Expert Committee on Drug Dependence have passed pentazocine as being safe for use without special controls on three occasions (W.H.O. Technical Reports, 1966, 1969, 1970). It has been widely used for the relief of postoperative pain (Kantor, Sunshine, Laska, Meisner, and Hopper, 1966) in the management of patients with malignant dis-ase (Beaver, Wallenstein, Houde, and Rogers, 1968; Frankendal and Kjellgren, 1971), ischaemic heart (Scott and Orr, 1969) and limb pain (Taylor, 1971), and in obstetric practice (Mitchell, 1963; Filler and Filler, 1966). In two uncontrolled trials (Vignon, Chapuy, and Falconnet, 1969; DavidChausse and Laporte, 1970), it was suggested that injections of pentazocine in doses ranging from 30 to 120 mg. per day were highly effective in patients with a variety of rheumatic diseases. The marketing of an oral preparation in 1969 made it possible to consider the use of pentazocine as a practical possibility in the long-term management of rheumatoid arthritis, although it was found to be only one-third as effective as the parenteral preparation on clinical assessment (Beaver, 1968) and on monitoring blood levels (Beckett, Taylor, and Kourounakis, 1970). In considering the use of pentazocine for the treatment of rheumatoid arthritis, it is unlikely that it would be an effective form of therapy on its own. It possesses no anti-inflammatory or antipyretic activity (Sterling Winthrop Laboratories, Unpublished observations). Fremont-Smith and Bayles (1965) showed that even large doses of pethidine were less effective than salicylates in relieving symptoms in active rheumatoid arthritis, and it is generally accepted that, if adequate analgesia is to be obtained, drugs combining peripheral anti-inflammatory, analgesic, and antipyretic effects must be employed (Winter, 1966; Drug Ther. Bull., 1966). In this paper, we report the results of a doubleblind cross-over trial in which oral pentazocine and identical placebo tablets were given to patients who were receiving standard and stable regimes of nonsteroidal analgesic anti-inflammatory drugs but were obtaining inadequate relief of pain.