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Vol 17, No 3 (2020)
Review paper
Published online: 2020-08-30

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Second generation antipsychotics in the therapy of patients with negative symptoms of schizophrenia

Agata Szulc
Psychiatria 2020;17(3):134-144.


The pharmacotherapy of schizophrenia, and particularly its negative symptoms, is a difficult and complex process. It is
necessary to properly identify groups of patients, and especially individual patients, depending on the nature of negative
symptoms, i.e. whether they are primary or secondary, predominant or significant, or predominant and persistent.
The literature regarding the efficacy of various second-generation antipsychotics in the treatment of negative symptoms
is not uniform; the assessment of negative symptoms is based on different methods, and the studies involve diversified
patient groups where patients’ responses to the studied drugs probably vary depending on whether their negative
symptoms are significant, predominant or predominant and persistent. Moreover, a vast majority of studies concern the
general population of schizophrenic patients, where the intensity of negative symptoms was evaluated amongst other
parameters. All of these factors make it practically impossible to evaluate and compare these studies. In addition, the
selection of a second-generation anti-psychotic that would show superiority over others is also difficult.
As a part of this study, a review of the literature for randomized trials directly comparing second-generation key antipsychotics
used in the treatment of negative symptoms was performed. In most of the analyzed studies, no statistically
significant differences were found between the analyzed drugs (comparison of risperidone, amisulpride, aripiprazole,
and olanzapine between them). Only individual studies have shown that olanzapine is superior to risperidone in assessing
the effect of both drugs on negative symptoms. However, it should be emphasized that the results were characterized
by limited credibility in terms of the possibility of drawing conclusions about the direct influence of drugs on negative
symptoms. The reason for this state of affairs should be sought, i.a. in the fact that in these studies the obtained effects
were not adjusted for the confounding factors whose influence on negative symptoms was confirmed. However in
patients with predominant and persistent negative symptoms cariprazine is superior to risperidone.
Complementary analysis of secondary studies for the analysed drugs indicated greater efficacy of second-generation
antipsychotics over first-generation drugs and placebo in various groups of patients with negative symptoms.
It must be underlined, however, that these studies are difficult to compare due to their non-homogeneity.
Another problem that arises in the context of clinical trials and daily practice it the proper diagnosis and differentiation
of primary negative symptoms from secondary negative symptoms.

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