If this debate were held 25 years ago I would probably be taking the position that chlorpromazine is the best ever. The fact that this lecture is taking place now could well be a result of the fact that almost all of the second generation antipsychotics are now off patent. This debate would have been far more important 10 or 15 years ago when the question clearly had huge economic importance. In those days I did not succeed in getting this issue into any major psychiatric forum. After CATIE and CUTLASS and numerous subsequent works few would argue today that the atypical antipsychotics are more effective clinically than the first generation ones (I exclude from this debate clozapine). The claim that second generation antipsychotics have a stronger effect on negative symptoms has completely disappeared from the psychiatric literature. These new antipsychotics cause less EPS and tardive dyskinesia, but the price our patients have paid in metabolic side effects is huge and it is really a tough choice as to which side effect is worse. The amount of propaganda “spin” that we have heard over the last 20 years about these issues is indeed discouraging: for instance the claim that atypical antipsychotics do not cause metabolic disturbance but that these disturbances are part in parcel of the illness. Recent studies demonstrate conclusively that even a single dose of olanzapine to normal volunteers causes a 45% increase in the area under the curve in a glucose tolerance test.

It is possible that in the future we will have antipsychotics that cause neither EPS nor metabolic disturbances and I am moderately optimistic about two new compounds in this regard. However, this is a far cry from our field's claim that a slew of new patented compounds were all far better than haloperidol and equivalent to clozapine without agranulocytosis. I am optimistic that in the long run that we will find better antipsychotics, but overpromising will not get us there any faster. In this sense haloperidol is the best ever.