Geographical variation in antipsychotic efficacy not ruled out

By Eleanor McDermid, Senior medwireNews Reporter

An individual patient data meta-analysis fails to exclude the possibility that atypical antipsychotics work better in patients from some parts of the world than others.

The analysis of data from 5233 patients with schizophrenia suggests that patients in North America may not respond as well as patients from Europe and the rest of the world.

These findings may indicate that “study results cannot be extrapolated from one geographical region to the others”, say study author Taina Mattila (Medicines Evaluation Board, Utrecht, the Netherlands) and co-workers.

They say that the variation found could be caused by differences in patient populations across the regions studied, particularly in age and ethnicity.

The differences between North America and other geographical regions did not quite attain statistical significance, but the authors say this could be due to much smaller patient numbers for the other regions. The raw data obtained for 22 of 29 studies that met the inclusion criteria included 3737 patients from North America, 1052 from Europe and just 444 from the rest of the world.

Pooled data for all five compounds studied showed an effect size of 0.368 for North America, with the prediction interval of 0.15–0.58 suggesting a small to moderate effect. But the potential effects were moderate to large in Europe and the rest of the world, with effect sizes of 0.564 and 0.530 and prediction intervals of 0.35–0.78 and 0.38–0.68, respectively.

Likewise, the odds ratios for response with an antipsychotic versus placebo were 1.71 for North America and 2.25 and 2.61 for Europe and the rest of the world, respectively.

Just two of the five compounds had individually been studied in all three regions. When the authors analysed data for these two antipsychotics separately, they found a similar pattern, with one having a trend towards greater efficacy in Europe only and the other in both Europe and the rest of the world, relative to North America.

This shows that the previously reported differences “are not driven by unequal distribution of studied compounds across the three regions” write Mattila et al in European Neuropsychopharmacology.

They add that, when looking at interaction, the threshold for a clinically significant effect size is “commonly more lenient than the traditional 0.5 level.”

They say: “We therefore conclude that clinically relevant regional differences in effect size between North America and the rest of the world cannot be excluded.”

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