More evidence on proneurocognitive effects of add-on mirtazapine in schizophrenia.

Enhancement of neurocognition is essential in the treatment of schizophrenia. In our previously reported six-week randomized controlled trial (RCT) mirtazapine added to conventional antipsychotics improved not only negative, but also positive symptoms and neurocognition in difficult-to-treat schizophrenia. The present study aimed to explore whether a prolonged exposure to mirtazapine could further improve neurocognition. Completers of the RCT who were able and willing to proceed to the extension phase received open label mirtazapine for an additional 6 weeks. During the extension phase, both groups (i.e., patients who previously received mirtazapine and those who received placebo) and the whole population showed improvement on a number of neurocognitive tests. Patients who shifted to open label mirtazapine from placebo achieved in the six following weeks similar results as their initially mirtazapine-treated counterparts did during their first 6 weeks of mirtazapine exposure. Middle-term mirtazapine treatment (12 weeks) demonstrated an advantage over short-term mirtazapine treatment (6 weeks) on Stroop Dots time and Trail Making Test, part B, number of mistakes (t = -2.562, p = 0.035 and t = -2.42, p = 0.043, correspondingly). Mirtazapine added to antipsychotics consistently shows desirable effects on neurocognition. Lengthy treatment seems worthwhile. Mirtazapine may become a safe and cost-saving neurocognitive enhancer in schizophrenia, yet more studies are needed.

Effects of add-on mirtazapine on neurocognition in schizophrenia: a double-blind, randomized, placebo-controlled study.

Mirtazapine added to antipsychotics appears to improve the clinical picture of schizophrenia, including both negative and positive symptoms. This study explored the effect of adjunctive mirtazapine on neurocognition in patients with schizophrenia who had shown an insufficient response to first-generation antipsychotics (FGAs). Thirty-seven schizophrenia patients, who were at least moderately ill despite their FGA treatment, received add-on mirtazapine (n=19) or placebo (n=18) in a 6-wk double-blind, randomized trial. Widely used neuropsychological tests were performed to explore visual-spatial functions, verbal and visual memory, executive functions, verbal fluency and general mental and psychomotor speed. The data were analysed on the modified intent-to-treat basis with last observation carried forward. False discovery rate was applied to correct for multiple testing. Mirtazapine outperformed placebo in the domains of visual-spatial ability and general mental speed/attentional control as assessed by, correspondingly, Block Design and Stroop dots. The difference in the degree of change (i.e. change while on mirtazapine minus that on placebo) was 18.6% (p=0.044) and 11.1% (p=0.044), respectively. Adjunctive mirtazapine might offer a safe, effective and cost-saving option as a neurocognitive enhancer for FGA-treated schizophrenia patients. Mirtazapine+FGA combinations may become especially useful in light of the currently increasing attention towards FGAs. Larger and longer studies that incorporate functional outcomes, as well as comparisons with second-generation antipsychotics are, however, still needed for more definite conclusions.

Add-on mirtazapine enhances antipsychotic effect of first generation antipsychotics in schizophrenia: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Mirtazapine, an antidepressant with a broad spectrum of receptor affinity may, if combined with first generation antipsyhotics (FGAs), improve clinical profile of the FGAs. However, potentiation of the antipsychotic effect by mirtazapine has not been reported thus far. We explored the efficacy of adjunctive mirtazapine on symptoms of schizophrenia in patients having an insufficient response to different FGAs. METHODS: Schizophrenia-diagnosed patients with a prolonged disease and a history of a poor response to numerous antipsychotics, who were at least moderately ill despite their FGAs treatment, received add-on mirtazapine (n=20) or placebo (n=19) in a 6-week double-blind randomized controlled trial (RCT). The analysis was made on a Modified Intent-to-Treat (MITT) basis with Last Observations Carried Forward (LOCF). RESULTS: Mirtazapine outranged placebo on almost all measures. The clear-cut clinical relevance of this finding was demonstrated by a large effect size of 1.00 (95% CI 0.23-1.67, p=0.003) on the total Positive and Negative Syndrome Scale (PANSS) scores (the primary outcome). The PANSS positive subscale scores decreased by 17.2% with mirtazapine vs. 1.6% with placebo (p<0.001), and the PANSS negative subscale scores by 12% and 3% (p<0.001), correspondingly. CONCLUSIONS: This is the first RCT reporting a robust additive antipsychotic effect of an adjunctive antidepressant. Mirtazapine-FGAs combination appears to be a safe, well-tolerated and efficacious treatment option in this challenging population. These findings are important due to the current re-emerging attention to FGAs. The focus of further studies should be expanded to include combinations with or switching to novel antipsychotics, different subpopulations of patients with schizophrenia, finding of optimal doses, and comparison with clozapine.