Adjunct mirtazapine for negative symptoms of schizophrenia.
Author(s): Phan SV, Kreys TJ.
Affiliation(s): University of Georgia College of Pharmacy, Albany, Georgia 31701, USA.
sphan@rx.uga.edu
Publication date & source: 2011, Pharmacotherapy. , 31(10):1017-30
Negative symptoms of schizophrenia are characterized by affective flattening,
alogia, avolition, and anhedonia and are often nonresponsive to antipsychotic
therapy. Because negative symptoms are predictive of poor occupational and social
functioning, as well as poor global outcomes, numerous studies evaluating adjunct
therapy to antipsychotics have been conducted. This review focuses on the use of
the antidepressant mirtazapine as adjunct therapy to antipsychotics for the
treatment of negative symptoms of schizophrenia. A literature search of the
MEDLINE database (from inception-March 2011) identified eight relevant articles:
six were randomized, double-blind, placebo-controlled trials, and two were
open-label trials. Of the six randomized trials reviewed, four studies assessed
add-on mirtazapine to second-generation antipsychotics, whereas two studies
examined add-on mirtazapine to first-generation antipsychotics. Five of the six
randomized trials supported the use of mirtazapine for negative symptoms of
schizophrenia. Of the two open-label trials, one naturalistic study demonstrated
that mirtazapine add-on therapy to clozapine was not associated with improvements
in negative symptoms; however, this study focused primarily on improvements in
cognition, not negative symptoms. An open-label extension phase to a randomized
controlled trial showed that mirtazapine continued to produce significant
improvement in negative symptoms over a longer duration of time, when added to
first-generation antipsychotic therapy. Overall, mirtazapine appears to be well
tolerated and associated with few drug interactions. Although adjunct mirtazapine
to antipsychotics has been shown to be effective at doses of 30 mg/day in most of
the trials, limitations of these studies include short study duration and small
sample sizes. To improve generalizability, larger multicenter studies with
broader inclusion criteria should be conducted. In addition, studies of longer
duration that use different mirtazapine dosages are needed to further assess the
benefits of mirtazapine for negative symptoms of schizophrenia.
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