Singh SP, Singh V, Kar N, et al. Efficacy of antidepressants in treating the negative symptoms of chronic schizophrenia: meta-analysis

University of Wolverhampton and Step to Health, Wolverhampton City Primary Care Trust, UK.
The British journal of psychiatry: the journal of mental science (Impact Factor: 7.99). 09/2010; 197(3):174-9. DOI: 10.1192/bjp.bp.109.067710
Source: PubMed


Treatment of negative symptoms in chronic schizophrenia continues to be a major clinical issue.
To analyse the efficacy of add-on antidepressants for the treatment of negative symptoms of chronic schizophrenia.
Systematic review and meta-analysis of randomised controlled trials comparing the effect of antidepressants and placebo on the negative symptoms of chronic schizophrenia, measured through standardised rating scales. Outcome was measured as standardised mean difference between end-of-trial and baseline scores of negative symptoms.
There were 23 trials from 22 publications (n = 819). The antidepressants involved were selective serotonin reuptake inhibitors, mirtazapine, reboxetine, mianserin, trazodone and ritanserin; trials on other antidepressants were not available. The overall standardised mean difference was moderate (-0.48) in favour of antidepressants and subgroup analysis revealed significant responses for fluoxetine, trazodone and ritanserin.
Antidepressants along with antipsychotics are more effective in treating the negative symptoms of schizophrenia than antipsychotics alone.

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    • "Indeed, a number of medications have been studied as adjuncts to antipsychotics with a goal to improve positive, negative , affective, or cognitive symptoms of schizophrenia resistant to antipsychotic medication alone. These pharmacological agents include lithium, anticonvulsants, antiinflammatory and glutamatergic drugs, sex hormones, cholinesterase and phosphodiesterase inhibitors, and various antidepressants (Singh et al., 2010; Leucht et al., 2011; Vernon et al., 2014). Although the use of antidepressants added to antipsychotics in schizophrenia has been a subject of intensive research during the recent decades, the evidence regarding their efficacy still remains conflicting (Hinkelmann et al., 2013). "
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    ABSTRACT: Despite adequate treatment with antipsychotics, a substantial number of patients with schizophrenia demonstrates only suboptimal clinical outcome. To overcome this challenge, various psychopharmacological combination strategies have been used, including antidepressants added to antipsychotics. To analyse the efficacy of add-on antidepressants for the treatment of negative, positive, cognitive, depressive and antipsychotic-induced extrapyramidal symptoms in schiz-ophrenia, published randomized controlled trials (RCTs) assessing the efficacy of adjunctive antidepressants in schizophrenia were reviewed using the following parameters: baseline clinical characteristics and number of patients, their on-going antipsychotic treatment, dosage of the add-on antidepressants, duration of the trial, efficacy measures, and outcomes. There were 36 RCTs reported in 41 journal publications (n=1582). The antidepres-sants used were: the Selective Serotonin Reuptake Inhibitors (SSRIs), duloxetine, imipra-mine, mianserin, mirtazapine, nefazodone, reboxetin, trazodone and bupropion. Mirtazapine and mianserin showed somewhat consistent efficacy for negative symptoms and both seemed to enhance neurocognition. Trazodone and nefazodone appeared to improve the antipsychotics-induced extrapyramidal symptoms. Imipramine and duloxetine tended to im-prove depressive symptoms. No clear evidence supporting SSRIs' efficacy on any clinical domain of schizophrenia was found. Add-on antidepressants did not worsen psychosis. Despite a substantial number of RCTs the overall efficacy of add-on antidepres-sants in schizophrenia remains uncertain mainly due to methodological issues. Some differ-ences in efficacy on several schizophrenia domains seem however to exist and to vary by the antidepressant subgroups - plausibly due to differences in the mechanisms of action. Antide-pressants may not worsen the course of psychosis. Better designed, larger and longer RCTs are needed. © The Author 2015. Published by Oxford University Press on behalf of CINP.
    Full-text · Article · May 2015 · The International Journal of Neuropsychopharmacology
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    • "Apart from a weak statistically significant but clinically negligible improvement in the negative symptoms , there was no change on any of the rating scales. A slight improvement in the negative symptoms of schizophrenia on antidepressant treatment is a wellknown phenomenon, although its pathomechanism is still uncertain (Singh et al., 2010). This study confirmed an earlier report that amineptine could reduce the severity of negative symptoms in some patients with schizophrenia (Volterra et al., 1990). "
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    ABSTRACT: Over the past two decades, there has been an upsurge of interest in catatonia, which is reflected in the attention it received in DSM 5, where it appears as a separate subsection of the Schizophrenia Spectrum and Other Psychotic Disorders (APA, 2013). This commentary argues that due to the lack of solid scientific evidence, the extended coverage of catatonia in DSM 5 was a premature, and consequently, a necessarily ambiguous decision. The psychopathological foundations of the modern catatonia concept are lacking therefore its boundaries are fuzzy. There are only a few, methodologically sound clinical, treatment response and small-scale neurobiological studies. The widely recommended use of benzodiazepines for the treatment of catatonia is based on case reports and open-label studies instead of placebo-controlled, randomized trials. In conclusion, the catatonic concept espoused by DSM 5 is necessarily vague reflecting the current state of knowledge.
    Full-text · Article · Dec 2014 · Neuropsychopharmacologia Hungarica: a Magyar Pszichofarmakológiai Egyesület lapja = official journal of the Hungarian Association of Psychopharmacology
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    • "In a meta-analysis which examined the efficacy of different secondgeneration antipsychotics, most were found not to provide a significant benefit over and above first-generation drugs, and in those that did the effect sizes were small (Leucht et al. 2009). Meta-analyses into the efficacy of adjunctive medications such as α 2 receptor antagonists (Hecht & Landy, 2012) and glutamatergic compounds (Tuominen et al. 2005) show some promise, while there is some evidence to suggest that adjunctive antidepressant medication may have some limited benefit (Singh et al. 2010). In a broader review evaluating the different pharmacological approaches in treating negative symptoms (Arango et al. 2013), new drugs that act on the NMDA and α 7 nicotinic receptors are highlighted as promising, but again more research is needed. "
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    ABSTRACT: Background: Negative symptoms are a core component of schizophrenia which can severely impact quality of life and functional outcomes. These symptoms are understood to be highly stable but this has not been tested in a meta-analysis, despite the wealth of longitudinal data available. Method: A systematic review of the literature was conducted, with eligible studies pooled into a random-effects meta-analysis. Planned meta-regressions were conducted to evaluate the impact of factors known to induce secondary negative symptoms, in addition to other possible sources of heterogeneity. Results: The main analysis included 89 samples from 41 studies, totalling 5944 participants. Negative symptoms were found to significantly reduce in all treatment interventions, including in placebo and treatment as usual conditions, with a medium effect size (ES) present across all study conditions (ES = 0.66, 95% confidence interval 0.56-0.77, I(2) = 94.0%). In a multivariate meta-regression, only the type of scale used was found to significantly influence negative symptom change. No difference in outcome was found between studies that excluded patients with a high level of positive or depressive symptoms, compared to those that did not. Conclusions: Negative symptoms were found to reduce in almost all schizophrenia outpatient samples. A reduction was found across all conditions, with effect sizes ranging from small to large depending upon the condition type. These findings challenge the convention that negative symptoms are highly stable and suggest that they may improve to a greater extent than what has previously been assumed.
    Full-text · Article · Nov 2014 · Psychological Medicine
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