Efficacy and safety of noradrenalin reuptake inhibitor augmentation therapy for schizophrenia: A meta-analysis of double-blind randomized placebo-controlled trials

Kishi, Taro; Mukai, Tomohiko; Matsuda, Yuki; Moriwaki, Masatsugu; Iwata, Nakao

doi:10.1016/j.jpsychires.2013.07.003

Cited by 11 publications

(10 citation statements)

References 51 publications

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“…Given the importance of maintaining medication adherence for schizophrenia, it is often necessary to use a safer but less efficacious antipsychotic. Augmentation therapy should be considered before changing from the safer antipsychotic to one with greater potential efficacy but also higher metabolic risk 41,42. In a prospective study, 27% of patients with schizophrenia eventually developed poor adherence 43.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and tolerability of topiramate-augmentation therapy for schizophrenia: a systematic review and meta-analysis of randomized controlled trials

Okuyama¹,

Oya²,

Matsunaga³

et al. 2016

NDT

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This study aimed to perform a comprehensive meta-analysis of topiramate-augmentation therapy in patients with schizophrenia receiving antipsychotic agents. Data published up to June 20, 2016 were obtained from the PubMed, PsycINFO, and Cochrane Library databases. Twelve randomized controlled trials comparing topiramate to placebo or antipsychotic only were included (n=676 patients). The primary outcome was change in overall symptoms. Relative risk (RR) and standardized mean difference (SMD), along with 95% confidence intervals, were calculated using random effects model for each outcome. Topiramate-augmentation therapy was superior to the control for decreasing overall symptoms (SMD −0.55, 95% confidence interval −0.86 to −0.24; P=0.001; I2=55%, eight comparisons, n=380), positive symptoms (SMD −0.4), negative symptoms (SMD −0.47), and Positive and Negative Syndrome Scale general subscale scores (SMD −0.67). Furthermore, topiramate-augmentation therapy decreased weight (SMD −0.69) and body mass index (SMD −0.95) compared with the control. Topiramate was similar to the control with respect to discontinuation due to all causes (RR 1.19), inefficacy (RR 1.71), and adverse events (RR 1.09). Topiramate was associated with higher incidence of paresthesia (RR 2.67) and attention difficulty (RR 8.97) compared with the control. Our results seemed to suggest that topiramate-augmentation therapy improves the psychopathology of schizophrenia with good tolerability and has the additional advantage of weight maintenance. However, because there were some limitations (numbers of studies and patients included in the meta-analysis were small, some studies used completer analysis, Chinese studies were included in the meta-analysis, and studies that had a risk of bias were included in the meta-analysis) in this study, we cannot apply the results of this study in daily clinical practice.

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Section: Discussionmentioning

confidence: 99%

Efficacy and tolerability of topiramate-augmentation therapy for schizophrenia: a systematic review and meta-analysis of randomized controlled trials

Okuyama¹,

Oya²,

Matsunaga³

et al. 2016

NDT

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“…The keywords for the search were (reboxetine OR Edronax) AND (schizophrenic disorder OR disorder, schizophrenic OR schizophrenic disorders OR schizophrenia OR dementia praecox). Reference lists from review articles [10,12,[31][32][33][34] were hand-searched for additional studies. First/ corresponding authors were contacted for missing information, whenever necessary.…”

Section: Study Selectionmentioning

confidence: 99%

“…The efficacy of reboxetine in treating negative symptoms and/ or reducing AP-induced weight gain in schizophrenia have been examined in meta-analyses [10,12,[31][32][33][34]. Common limitations of these meta-analyses include the small number of included studies, resulting in insufficient power.…”

Section: Introductionmentioning

confidence: 99%

“…Common limitations of these meta-analyses include the small number of included studies, resulting in insufficient power. For example, 3 meta-analyses [12,33,34], each with 2 RCTs (n = 85) [18,22], found that reboxetine was superior to placebo in reducing AP-induced weight gain. Another meta-analysis [31] included 9 RCTs, but one of them was an open-label study [35], the inclusion of which violated standard recommendations [36].…”

Section: Introductionmentioning

confidence: 99%

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Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials

Zheng

Shi

et al. 2019

Pharmacopsychiatry

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Background Results of previous studies on the safety and efficacy of adjunctive reboxetine for schizophrenia have been inconsistent. Aim The aim of this study was to examine the efficacy and tolerability of reboxetine as an adjunct medication to antipsychotic treatment in a meta-analysis of randomized controlled trials (RCTs). Methods Two independent investigators extracted data for a random effects meta-analysis and assessed the quality of studies using risk of bias and the Jadad scale. Weighted and standardized mean differences (WMDs/SMDs) and risk ratio (RR)±95% confidence intervals (CIs) were calculated. Results Nine RCTs (n=630) with double-blind design were identified. Reboxetine outperformed placebo in improving negative (9 RCTs, n=602, SMD: −0.47 [95% CI: −0.87, −0.07], p=0.02; I2=82%), but not the overall, positive, and general psychopathology scores. The significant therapeutic effect on negative symptoms disappeared in the sensitivity analysis after removing an outlying study and in 50% (6/12) of the subgroup analyses. Reboxetine outperformed placebo in reducing weight (3 RCTs, n=186, WMD: −3.83 kg, p=0.04; I2=92%) and body mass index (WMD: −2.23 kg/m2, p=0.04; I2=95%). Reboxetine caused dry mouth but was associated with less weight gain overall and weight gain of ≥7% of the initial weight. All-cause discontinuation and other adverse events were similar between reboxetine and placebo. Conclusion Adjunctive reboxetine could be useful for attenuating antipsychotic-induced weight gain, but it was not effective in treating psychopathology including negative symptoms in schizophrenia.

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“…Anti-depressants may treat depressive symptoms, but are generally without effect on positive or negative symptoms [26]…”

Section: Pharmacological Treatmentmentioning

confidence: 99%

Current and Emergent Treatments for Symptoms and Neurocognitive Impairment in Schizophrenia

Javitt

2014

Curr Treat Options Psych

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Efficacy and safety of noradrenalin reuptake inhibitor augmentation therapy for schizophrenia: A meta-analysis of double-blind randomized placebo-controlled trials

Cited by 11 publications

References 51 publications

Efficacy and tolerability of topiramate-augmentation therapy for schizophrenia: a systematic review and meta-analysis of randomized controlled trials

Efficacy and tolerability of topiramate-augmentation therapy for schizophrenia: a systematic review and meta-analysis of randomized controlled trials

Adjunctive Reboxetine for Schizophrenia: Meta-analysis of Randomized Double-blind, Placebo-controlled Trials

Current and Emergent Treatments for Symptoms and Neurocognitive Impairment in Schizophrenia

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