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Eur Arch Psychiatry Clin Neurosci. 2015 Oct;265(7):567-78. doi: 10.1007/s00406-015-0596-y. Epub 2015 Apr 21.

Pharmacological treatment of negative symptoms in schizophrenia.

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Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany.
Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary.
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.


Effective treatment of negative symptoms is one of the most important unmet needs in schizophrenic disorders. Because the evidence on current psychopharmacological treatments is unclear, the authors reviewed the findings published to date by searching PubMed with the keywords negative symptoms, antipsychotics, antidepressants, glutamatergic compounds, monotherapy and add-on therapy and identifying additional articles in the reference lists of the resulting publications. The findings presented here predominantly focus on results of meta-analyses. Evidence for efficacy of current psychopharmacological medications is difficult to assess because of methodological problems and inconsistent results. In general, the second-generation antipsychotics (SGAs) do not appear to have good efficacy in negative symptoms, although some show better efficacy than first-generation antipsychotics, some of which also demonstrated efficacy in negative symptoms. Specific trials on predominant persistent negative symptoms are rare and have been performed with only a few SGAs. More often, trials on somewhat persistent negative symptoms evaluate add-on strategies to ongoing antipsychotic treatment. Such trials, mostly on modern antidepressants, have demonstrated some efficacy. Several trials with small samples have evaluated add-on treatment with glutamatergic compounds, such as the naturally occurring amino acids glycine and D-serine and new pharmacological compounds. The results are highly inconsistent, although overall efficacy results appear to be positive. The unsatisfactory and inconsistent results can be partially explained by methodological problems. These problems need to be solved in the future, and the authors propose some possible solutions. Further research is required to identify effective treatment for the negative symptoms of schizophrenia.


Antidepressants; Antipsychotics; Glutamatergic compounds; Negative symptoms; Pharmacological treatment

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