Meta-analysis of noradrenergic and specific serotonergic antidepressant use in schizophrenia

Taro Kishi; Nakao Iwata

doi:10.1017/S1461145713000667

Meta-analysis of noradrenergic and specific serotonergic antidepressant use in schizophrenia

Psychiatry

Research output: Contribution to journal › Review article › peer-review

28 Citations (Scopus)

Abstract

We examined whether noradrenergic and specific serotonergic antidepressants (NaSSAs: mirtazapine and mianserin), as augmentation therapy, have therapeutic potential for schizophrenia treatment. A systematic review was conducted of PubMed, Cochrane Library and PsycINFO in December 2012 and meta-analyses of double-blind, randomized placebo-controlled trials were performed. Standardized mean difference (SMD), risk ratio (RR), number-needed-to-treat (NNT), number-needed-to-harm (NNH) and 95% confidence intervals (CI) were calculated. Results were across 12 studies and 362 patients were included (mirtazapine: seven trials and 221 patients; mianserin: five trials and 141 patients). NaSSA augmentation therapy was superior to placebo in overall symptoms (s.m.d.Â =Â-0.75, CI-1.24 to-0.26, pÂ =Â 0.003, NÂ =Â 11, nÂ =Â 301), negative symptoms (s.m.d.Â =Â-0.88, CI-1.41 to-0.34, pÂ =Â 0.001, NÂ =Â 9, nÂ =Â 240) and response rate (RRÂ =Â 0.71, CI 0.57-0.88, pÂ =Â 0.002, NNTÂ =Â 4, p<0.00001, NÂ =Â 6, nÂ =Â 163). There was no significant difference in positive symptoms, depressive symptoms or discontinuation rate between NaSSAs and placebo treatments. In addition, no patients who received NaSSAs developed worsening psychosis during the study. For individual NaSSAs, mirtazapine was superior to placebo in overall symptoms (s.m.d.Â =Â 0.98, CIÂ =Â-1.74 to-0.22, pÂ =Â 0.01, NÂ =Â 7, nÂ =Â 194), negative symptoms (s.m.d.Â =Â-1.25, CI-1.88 to-0.62, pÂ =Â 0.0001, NÂ =Â 6, nÂ =Â 172) and response rate (RRÂ =Â 0.70, pÂ =Â 0.04, NNTÂ =Â 4, pÂ =Â 0.0004, NÂ =Â 4, nÂ =Â 119). Moreover, NaSSAs were associated with reduced akathisia score (pÂ <Â 0.00001) and extrapyramidal symptom scales (pÂ =Â 0.01). However, NaSSAs caused drowsiness/sedation/somnolence compared with placebo (RRÂ =Â 3.52, pÂ =Â 0.002, NNTÂ =Â 6, pÂ =Â 0.01, NÂ =Â 8, nÂ =Â 209). Our results indicate that NaSSA (especially mirtazapine) augmentation therapy improved overall and negative symptoms in patients with schizophrenia. Because the included studies were small, the results should be treated with caution.

Original language	English
Pages (from-to)	343-354
Number of pages	12
Journal	International Journal of Neuropsychopharmacology
Volume	17
Issue number	2
DOIs	https://doi.org/10.1017/S1461145713000667
Publication status	Published - 02-2014

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

All Science Journal Classification (ASJC) codes

Pharmacology
Psychiatry and Mental health
Pharmacology (medical)

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10.1017/S1461145713000667

Cite this

@article{9c28c5ec31c442bfbdd252f1f9a93f33,

title = "Meta-analysis of noradrenergic and specific serotonergic antidepressant use in schizophrenia",

abstract = "We examined whether noradrenergic and specific serotonergic antidepressants (NaSSAs: mirtazapine and mianserin), as augmentation therapy, have therapeutic potential for schizophrenia treatment. A systematic review was conducted of PubMed, Cochrane Library and PsycINFO in December 2012 and meta-analyses of double-blind, randomized placebo-controlled trials were performed. Standardized mean difference (SMD), risk ratio (RR), number-needed-to-treat (NNT), number-needed-to-harm (NNH) and 95\% confidence intervals (CI) were calculated. Results were across 12 studies and 362 patients were included (mirtazapine: seven trials and 221 patients; mianserin: five trials and 141 patients). NaSSA augmentation therapy was superior to placebo in overall symptoms (s.m.d.{\^A} ={\^A}-0.75, CI-1.24 to-0.26, p{\^A} ={\^A} 0.003, N{\^A} ={\^A} 11, n{\^A} ={\^A} 301), negative symptoms (s.m.d.{\^A} ={\^A}-0.88, CI-1.41 to-0.34, p{\^A} ={\^A} 0.001, N{\^A} ={\^A} 9, n{\^A} ={\^A} 240) and response rate (RR{\^A} ={\^A} 0.71, CI 0.57-0.88, p{\^A} ={\^A} 0.002, NNT{\^A} ={\^A} 4, p<0.00001, N{\^A} ={\^A} 6, n{\^A} ={\^A} 163). There was no significant difference in positive symptoms, depressive symptoms or discontinuation rate between NaSSAs and placebo treatments. In addition, no patients who received NaSSAs developed worsening psychosis during the study. For individual NaSSAs, mirtazapine was superior to placebo in overall symptoms (s.m.d.{\^A} ={\^A} 0.98, CI{\^A} ={\^A}-1.74 to-0.22, p{\^A} ={\^A} 0.01, N{\^A} ={\^A} 7, n{\^A} ={\^A} 194), negative symptoms (s.m.d.{\^A} ={\^A}-1.25, CI-1.88 to-0.62, p{\^A} ={\^A} 0.0001, N{\^A} ={\^A} 6, n{\^A} ={\^A} 172) and response rate (RR{\^A} ={\^A} 0.70, p{\^A} ={\^A} 0.04, NNT{\^A} ={\^A} 4, p{\^A} ={\^A} 0.0004, N{\^A} ={\^A} 4, n{\^A} ={\^A} 119). Moreover, NaSSAs were associated with reduced akathisia score (p{\^A} <{\^A} 0.00001) and extrapyramidal symptom scales (p{\^A} ={\^A} 0.01). However, NaSSAs caused drowsiness/sedation/somnolence compared with placebo (RR{\^A} ={\^A} 3.52, p{\^A} ={\^A} 0.002, NNT{\^A} ={\^A} 6, p{\^A} ={\^A} 0.01, N{\^A} ={\^A} 8, n{\^A} ={\^A} 209). Our results indicate that NaSSA (especially mirtazapine) augmentation therapy improved overall and negative symptoms in patients with schizophrenia. Because the included studies were small, the results should be treated with caution.",

author = "Taro Kishi and Nakao Iwata",

year = "2014",

month = feb,

doi = "10.1017/S1461145713000667",

language = "English",

volume = "17",

pages = "343--354",

journal = "International Journal of Neuropsychopharmacology",

issn = "1461-1457",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - Meta-analysis of noradrenergic and specific serotonergic antidepressant use in schizophrenia

AU - Kishi, Taro

AU - Iwata, Nakao

PY - 2014/2

Y1 - 2014/2

N2 - We examined whether noradrenergic and specific serotonergic antidepressants (NaSSAs: mirtazapine and mianserin), as augmentation therapy, have therapeutic potential for schizophrenia treatment. A systematic review was conducted of PubMed, Cochrane Library and PsycINFO in December 2012 and meta-analyses of double-blind, randomized placebo-controlled trials were performed. Standardized mean difference (SMD), risk ratio (RR), number-needed-to-treat (NNT), number-needed-to-harm (NNH) and 95% confidence intervals (CI) were calculated. Results were across 12 studies and 362 patients were included (mirtazapine: seven trials and 221 patients; mianserin: five trials and 141 patients). NaSSA augmentation therapy was superior to placebo in overall symptoms (s.m.d.Â =Â-0.75, CI-1.24 to-0.26, pÂ =Â 0.003, NÂ =Â 11, nÂ =Â 301), negative symptoms (s.m.d.Â =Â-0.88, CI-1.41 to-0.34, pÂ =Â 0.001, NÂ =Â 9, nÂ =Â 240) and response rate (RRÂ =Â 0.71, CI 0.57-0.88, pÂ =Â 0.002, NNTÂ =Â 4, p<0.00001, NÂ =Â 6, nÂ =Â 163). There was no significant difference in positive symptoms, depressive symptoms or discontinuation rate between NaSSAs and placebo treatments. In addition, no patients who received NaSSAs developed worsening psychosis during the study. For individual NaSSAs, mirtazapine was superior to placebo in overall symptoms (s.m.d.Â =Â 0.98, CIÂ =Â-1.74 to-0.22, pÂ =Â 0.01, NÂ =Â 7, nÂ =Â 194), negative symptoms (s.m.d.Â =Â-1.25, CI-1.88 to-0.62, pÂ =Â 0.0001, NÂ =Â 6, nÂ =Â 172) and response rate (RRÂ =Â 0.70, pÂ =Â 0.04, NNTÂ =Â 4, pÂ =Â 0.0004, NÂ =Â 4, nÂ =Â 119). Moreover, NaSSAs were associated with reduced akathisia score (pÂ <Â 0.00001) and extrapyramidal symptom scales (pÂ =Â 0.01). However, NaSSAs caused drowsiness/sedation/somnolence compared with placebo (RRÂ =Â 3.52, pÂ =Â 0.002, NNTÂ =Â 6, pÂ =Â 0.01, NÂ =Â 8, nÂ =Â 209). Our results indicate that NaSSA (especially mirtazapine) augmentation therapy improved overall and negative symptoms in patients with schizophrenia. Because the included studies were small, the results should be treated with caution.

AB - We examined whether noradrenergic and specific serotonergic antidepressants (NaSSAs: mirtazapine and mianserin), as augmentation therapy, have therapeutic potential for schizophrenia treatment. A systematic review was conducted of PubMed, Cochrane Library and PsycINFO in December 2012 and meta-analyses of double-blind, randomized placebo-controlled trials were performed. Standardized mean difference (SMD), risk ratio (RR), number-needed-to-treat (NNT), number-needed-to-harm (NNH) and 95% confidence intervals (CI) were calculated. Results were across 12 studies and 362 patients were included (mirtazapine: seven trials and 221 patients; mianserin: five trials and 141 patients). NaSSA augmentation therapy was superior to placebo in overall symptoms (s.m.d.Â =Â-0.75, CI-1.24 to-0.26, pÂ =Â 0.003, NÂ =Â 11, nÂ =Â 301), negative symptoms (s.m.d.Â =Â-0.88, CI-1.41 to-0.34, pÂ =Â 0.001, NÂ =Â 9, nÂ =Â 240) and response rate (RRÂ =Â 0.71, CI 0.57-0.88, pÂ =Â 0.002, NNTÂ =Â 4, p<0.00001, NÂ =Â 6, nÂ =Â 163). There was no significant difference in positive symptoms, depressive symptoms or discontinuation rate between NaSSAs and placebo treatments. In addition, no patients who received NaSSAs developed worsening psychosis during the study. For individual NaSSAs, mirtazapine was superior to placebo in overall symptoms (s.m.d.Â =Â 0.98, CIÂ =Â-1.74 to-0.22, pÂ =Â 0.01, NÂ =Â 7, nÂ =Â 194), negative symptoms (s.m.d.Â =Â-1.25, CI-1.88 to-0.62, pÂ =Â 0.0001, NÂ =Â 6, nÂ =Â 172) and response rate (RRÂ =Â 0.70, pÂ =Â 0.04, NNTÂ =Â 4, pÂ =Â 0.0004, NÂ =Â 4, nÂ =Â 119). Moreover, NaSSAs were associated with reduced akathisia score (pÂ <Â 0.00001) and extrapyramidal symptom scales (pÂ =Â 0.01). However, NaSSAs caused drowsiness/sedation/somnolence compared with placebo (RRÂ =Â 3.52, pÂ =Â 0.002, NNTÂ =Â 6, pÂ =Â 0.01, NÂ =Â 8, nÂ =Â 209). Our results indicate that NaSSA (especially mirtazapine) augmentation therapy improved overall and negative symptoms in patients with schizophrenia. Because the included studies were small, the results should be treated with caution.

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DO - 10.1017/S1461145713000667

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JO - International Journal of Neuropsychopharmacology

JF - International Journal of Neuropsychopharmacology

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Meta-analysis of noradrenergic and specific serotonergic antidepressant use in schizophrenia

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