Are Patients Really Getting Better?

Currently, Lamictal is undergoing phase III trials as an add-on treatment for schizophrenia. Here’s what a recent review had to say about research done to this point on lamotrigine as an add-on treatment…

“We found five relevant trials (total n=537), but no usable data on service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment or economic outcomes. Overall, reporting of data was poor. Those data we were able to use suggested that equal proportions of people allocated lamotrigine or placebo had no global response (n=208, 1 RCT, RR 1.06 CI 0.73 to 1.54). There was no significant difference between groups in the proportions of people whose mental state did not improve (n=297, 3 RCT, RR 1.26 CI 0.81 to 1.97). There was, however, a significant reduction in the PANSS total scores (n=67, 2 RCT, WMD -16.88 CI -8.57 to -25.18, p=0.0001), positive symptom sub-scale scores (n=65, 2 RCTs, WMD -5.10 CI -8.86 to -1.34) and negative symptom sub-scale scores (n=67, 2 RCTs, WMD -5.25, CI -7.07 to -3.43). Most cognitive measures showed no differences (n=329, 2 RCTs, RR not attaining BACS composite score of 0.5 1.10 CI 0.59 to 2.04).”

So the PANSS shows change, which is good, but on the other hand there was no usable data on a number of important variables. This brings up the issue of what is clinically relevant – what is the relationship between PANSS scores and real-life patient functioning? I’m not claiming to have the answer. If PANSS scores are changing yet mental state (however it was measured) is not also improving, what's going on? The question is important – if we have nothing but a single measure indicating improvement, does this mean a drug really benefits patients? Alan Kazdin discussed this point much more brilliantly than I could in an article in the American Psychologist recently. What made this of particular concern to me was the fact that no usable data were reported, across five trials, on a variety of other aspects of patient functioning – was this just a lack of curiosity on the part of investigators or were data suppressed? I’ve not dug deeply on this one, but it is a question worth thinking about.