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

Taro Kishi, Nakao Iwata

Research output: Contribution to journalReview article

18 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-0.75, CI-1.24 to-0.26, p = 0.003, N = 11, n = 301), negative symptoms (s.m.d. =Â-0.88, CI-1.41 to-0.34, p = 0.001, N = 9, n = 240) and response rate (RR = 0.71, CI 0.57-0.88, p = 0.002, NNT = 4, p<0.00001, N = 6, n = 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. = 0.98, CI =Â-1.74 to-0.22, p = 0.01, N = 7, n = 194), negative symptoms (s.m.d. =Â-1.25, CI-1.88 to-0.62, p = 0.0001, N = 6, n = 172) and response rate (RR = 0.70, p = 0.04, NNT = 4, p = 0.0004, N = 4, n = 119). Moreover, NaSSAs were associated with reduced akathisia score (p < 0.00001) and extrapyramidal symptom scales (p = 0.01). However, NaSSAs caused drowsiness/sedation/somnolence compared with placebo (RR = 3.52, p = 0.002, NNT = 6, p = 0.01, N = 8, n = 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 languageEnglish
Pages (from-to)343-354
Number of pages12
JournalInternational Journal of Neuropsychopharmacology
Volume17
Issue number2
DOIs
Publication statusPublished - 01-02-2014

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Antidepressive Agents
Meta-Analysis
Numbers Needed To Treat
Schizophrenia
Confidence Intervals
Placebos
Odds Ratio
Mianserin
Therapeutics
Psychomotor Agitation
Sleep Stages
PubMed
Psychotic Disorders
Libraries
Randomized Controlled Trials
Depression
mirtazapine

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

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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.",
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Meta-analysis of noradrenergic and specific serotonergic antidepressant use in schizophrenia. / Kishi, Taro; Iwata, Nakao.

In: International Journal of Neuropsychopharmacology, Vol. 17, No. 2, 01.02.2014, p. 343-354.

Research output: Contribution to journalReview article

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AU - Iwata, Nakao

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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-0.75, CI-1.24 to-0.26, p = 0.003, N = 11, n = 301), negative symptoms (s.m.d. =Â-0.88, CI-1.41 to-0.34, p = 0.001, N = 9, n = 240) and response rate (RR = 0.71, CI 0.57-0.88, p = 0.002, NNT = 4, p<0.00001, N = 6, n = 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. = 0.98, CI =Â-1.74 to-0.22, p = 0.01, N = 7, n = 194), negative symptoms (s.m.d. =Â-1.25, CI-1.88 to-0.62, p = 0.0001, N = 6, n = 172) and response rate (RR = 0.70, p = 0.04, NNT = 4, p = 0.0004, N = 4, n = 119). Moreover, NaSSAs were associated with reduced akathisia score (p < 0.00001) and extrapyramidal symptom scales (p = 0.01). However, NaSSAs caused drowsiness/sedation/somnolence compared with placebo (RR = 3.52, p = 0.002, NNT = 6, p = 0.01, N = 8, n = 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-0.75, CI-1.24 to-0.26, p = 0.003, N = 11, n = 301), negative symptoms (s.m.d. =Â-0.88, CI-1.41 to-0.34, p = 0.001, N = 9, n = 240) and response rate (RR = 0.71, CI 0.57-0.88, p = 0.002, NNT = 4, p<0.00001, N = 6, n = 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. = 0.98, CI =Â-1.74 to-0.22, p = 0.01, N = 7, n = 194), negative symptoms (s.m.d. =Â-1.25, CI-1.88 to-0.62, p = 0.0001, N = 6, n = 172) and response rate (RR = 0.70, p = 0.04, NNT = 4, p = 0.0004, N = 4, n = 119). Moreover, NaSSAs were associated with reduced akathisia score (p < 0.00001) and extrapyramidal symptom scales (p = 0.01). However, NaSSAs caused drowsiness/sedation/somnolence compared with placebo (RR = 3.52, p = 0.002, NNT = 6, p = 0.01, N = 8, n = 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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