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

Abstract

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.

Relationships between pharmacotherapy-induced metabolic changes and improved psychopathology in schizophrenia: data from a mirtazapine and first-generation antipsychotics combination trial

“…In our previous publications a clear-cut effect of add-on mirtazapine on schizophrenia symptoms was reported (Joffe et al 2009 ;Stenberg et al 2010 ;Terevnikov et al 2010), where significant improvement was observed in the main clinical domains of schizophrenia, as measured by PANSS total, positive, negative and general (sub)-scales and a battery of neurocognitive tests. In the present study, we explored the relationships between the metabolic and psychotropic effects of mirtazapine.…”

“…Mirtazapine, one of the few existing receptor-blocking antidepressants with a specific psychopharmacological profile, seems to boost the desirable effects of the FGAs on the negative, positive and cognitive symptoms of schizophrenia (Joffe et al 2009 ;Stenberg et al 2010 ;Terevnikov et al 2010 ;Phan and Kreys, 2011). Mirtazapine also causes weight gain and dyslipidaemia in patients with major depressive disorder (MDD ; Laimer et al 2006).…”

Predictors and mediators of add-on mirtazapine-induced cognitive enhancement in schizophrenia – A path model investigation

“…The participants (n ¼ 19 in the mirtazapine group and n ¼ 18 in the placebo group) were adults who were suffering from chronic schizophrenia and had previously demonstrated sub-optimal response to different FGAs. The study has been described thoroughly earlier (Joffe et al, 2009;Stenberg et al, 2010).…”

May Non-antipsychotic Drugs Improve Cognition of Schizophrenia Patients?

“…A following double-blind, randomized, placebo-controlled study failed to find differences between patients treated with adjunctive mirtazapine to atypical antipsychotic and controls [24]. In contrast, a similar study with a sample of schizophrenia patients treated with first generation antipsychotics showed the efficacy of adjunctive mirtazapine as neurocognitive enhancer [25]. The latter study was extended for a further 6 weeks and patients, who had already received mirtazapine, showed further improvements in some cognitive functions as shown by the scores in the Stroop Dots time and Trail Making Test part B [26].…”