There is a widely accepted traditional understanding among experts, that the therapeutic benefits of neuroleptic short and long-term treatment of people suffering from schizophrenic psychosis are so relevant for the life of these people as well as also from the viewpoint of the society that in comparison the typical side effects of the antipsychotic medication can be neglected. This position is expressed in all national and international guidelines, like for example the WFSBP guidelines. The efficacy of antipsychotics in reducing the symptoms of the acute episode as well as in relapse prevention are well documented in the sense of EBM and most of the side effects are only transient or can be reduced by adequate measures.

However this position probably has to be re-discussed given the fact that data coming from few naturalistic studies raised the question, whether long-term treatment with antipsychotics can lead to brain alterations which in consequence might be negative for brain functioning. This is a serious issue which needs further research in control group studies, because naturalistic studies are often biased in their results. Altogether the respective results are not consistent. One RCT and one naturalistic follow up study suggest that atypical antipsychotic like clozapine or olanzapine are not associated with brain volume changes. Also this needs further investigation as well as discussions concerning potential consequences for the current treatment procedures. Apparently in the treatment guidelines this differentiation so far was neglected.