Much discussion has occurred about the idea that different antipsychotics can be combined in order to reduce the dose and the side effect profile of each one. Present Guidelines do not support this approach.

We decided to carry out a literature review to establish the evidence which supports this approach.

We carried out a literature search using Google Scholar and Pubmed databases.

Clozapine augmentation with another antipsychotic, usually sulpiride, amisulpride or aripiprazole, has been most studied. Many studies focus on efficacy rather than side effect profile.

A number of short studies and case reports, often with the use of Aripiprazole as the augmenting medication,

suggest that combinations of antipsychotics can reduce side effect profile; larger studies are beginning to emerge.

Some of these studies do not demonstrate greater efficacy for the combination, and in these, the combination use can only be justified on the basis of improvement of side effect profile.

What can be done pragmatically in clinical trials is to compare the effect of a combination with that of each medication separately, or in some cases with placebo. Efficacy of the combination needs to be balanced against side effect profile.

Before this approach can be recommended in guidelines, it is necessary that more trials of larger samples need to be carried out.