Letters

Paracetamol-codeine combinations versus paracetamol alone

In a similar overview we also concluded that codeine added to the analgesic efficacy of paracetamol, using derived outcome measures of pain such as the sum of the pain intensity difference (as defined in de Craen and colleagues' paper).² In the meta-analysis of six head to head comparison trials, however, a significant pooled estimate of a 6.7 point difference in the sum of the pain intensity difference (95% confidence interval 3.2 to 10.3) between the paracetamol-codeine combination and paracetamol was not translated into a significant increase in the proportion of patients obtaining moderate to excellent pain relief (response rate ratio 1.14 (0.97 to 1.34)). More head to head comparisons will of course improve our ability to estimate additive effects.^{3 4}

Deciding what change is clinically important is often difficult. Better reporting of patients' assessment of how their treatments have affected their symptom or condition, as advocated by de Craen and colleagues, would ease the interpretation of data from clinical trials and facilitate evidence based practice. We would go one step further and request that the time at which this response is assessed should be defined consistently to take account of the drugs' pharmacokinetics and pharmacodynamics.

In our meta-analysis, caffeine (another additive in many products that combine analgesics) did not add to the efficacy of paracetamol, as measured by either the sum of the pain intensity difference or the response rate ratio.

Professor of clinical pharmaceutics Research fellow Centre for Evidence Based Pharmacotherapy, School of Pharmacy, University of Nottingham, Nottingham NG7 2RD

A Li Wan Po, W Y Zhang 

1. De Craen AJM, Di Guilio G, Lampe-Schoenmaeckers AJEM, Kessels AGH, Kleijnen J. Analgesic efficacy and safety of paracetamol-codeine combinations versus paracetamol alone: a systematic review. BMJ 1996;313:321-5. (10 August.) [Abstract/Free Full Text]
2. Zhang WY, Li Wan Po A. Analgesic efficacy of paracetamol and its combination with codeine and caffeine in surgical pain--a meta-analysis. J Clin Pharm Ther 1996 (in press).
3. Rothman KJ, Michels KB. The continuing unethical use of placebo controls. N Engl J Med 1994;331:394-8. [Free Full Text]
4. Jones B, Jarvis P, Lewis Ja, Ebbutt AF. Trials to show equivalence. BMJ 1996;313:36-9. (6 July.) [Free Full Text]