Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia

B. Galling; J. A. Vernon; A. K. Pagsberg; A. Wadhwa; E. Grudnikoff; A. J. Seidman; M. Tsoy-Podosenin; M. Poyurovsky; J. M. Kane; C. U. Correll

doi:10.1111/acps.12854

Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia

B. Galling, J. A. Vernon, A. K. Pagsberg, A. Wadhwa, E. Grudnikoff, A. J. Seidman, M. Tsoy-Podosenin, M. Poyurovsky, J. M. Kane, C. U. Correll^*

^*Corresponding author for this work

Department of Clinical Medicine

29 Citations (Scopus)

Abstract

Objective: To evaluate the efficacy and safety of antidepressant augmentation of antipsychotics in schizophrenia. Methods: Systematic literature search (PubMed/MEDLINE/PsycINFO/Cochrane Library) from database inception until 10/10/2017 for randomized, double-blind, efficacy-focused trials comparing adjunctive antidepressants vs. placebo in schizophrenia. Results: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = −0.37, 95% confidence interval (CI) = −0.57 to −0.17, P < 0.001], driven by negative (SMD = −0.25, 95% CI = −0.44–0.06, P = 0.010), but not positive (P = 0.190) or general (P = 0.089) symptom reduction. Superiority regarding negative symptoms was confirmed in studies augmenting first-generation antipsychotics (FGAs) (SMD = −0.42, 95% CI = −0.77, −0.07, P = 0.019), but not second-generation antipsychotics (P = 0.144). Uniquely, superiority in total symptom reduction by NaSSAs (SMD = −0.71, 95% CI = −1.21, −0.20, P = 0.006) was not driven by negative (P = 0.438), but by positive symptom reduction (SMD = −0.43, 95% CI = −0.77, −0.09, P = 0.012). Antidepressants did not improve depressive symptoms more than placebo (P = 0.185). Except for more dry mouth [risk ratio (RR) = 1.57, 95% CI = 1.04–2.36, P = 0.03], antidepressant augmentation was not associated with more adverse events or all-cause/specific-cause discontinuation. Conclusions: For schizophrenia patients on stable antipsychotic treatment, adjunctive antidepressants are effective for total and particularly negative symptom reduction. However, effects are small-to-medium, differ across antidepressants, and negative symptom improvement seems restricted to the augmentation of FGAs.

Original language	English
Journal	Acta Psychiatrica Scandinavica
Volume	137
Issue number	3
Pages (from-to)	187-205
ISSN	0001-690X
DOIs	https://doi.org/10.1111/acps.12854
Publication status	Published - 2018

Keywords

antidepressives
psychopharmacology
psychosis
schizophrenia
treatment

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10.1111/acps.12854

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@article{36d7c221501a419f90b0064b633fcda5,

title = "Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia",

abstract = "Objective: To evaluate the efficacy and safety of antidepressant augmentation of antipsychotics in schizophrenia. Methods: Systematic literature search (PubMed/MEDLINE/PsycINFO/Cochrane Library) from database inception until 10/10/2017 for randomized, double-blind, efficacy-focused trials comparing adjunctive antidepressants vs. placebo in schizophrenia. Results: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = −0.37, 95% confidence interval (CI) = −0.57 to −0.17, P < 0.001], driven by negative (SMD = −0.25, 95% CI = −0.44–0.06, P = 0.010), but not positive (P = 0.190) or general (P = 0.089) symptom reduction. Superiority regarding negative symptoms was confirmed in studies augmenting first-generation antipsychotics (FGAs) (SMD = −0.42, 95% CI = −0.77, −0.07, P = 0.019), but not second-generation antipsychotics (P = 0.144). Uniquely, superiority in total symptom reduction by NaSSAs (SMD = −0.71, 95% CI = −1.21, −0.20, P = 0.006) was not driven by negative (P = 0.438), but by positive symptom reduction (SMD = −0.43, 95% CI = −0.77, −0.09, P = 0.012). Antidepressants did not improve depressive symptoms more than placebo (P = 0.185). Except for more dry mouth [risk ratio (RR) = 1.57, 95% CI = 1.04–2.36, P = 0.03], antidepressant augmentation was not associated with more adverse events or all-cause/specific-cause discontinuation. Conclusions: For schizophrenia patients on stable antipsychotic treatment, adjunctive antidepressants are effective for total and particularly negative symptom reduction. However, effects are small-to-medium, differ across antidepressants, and negative symptom improvement seems restricted to the augmentation of FGAs.",

keywords = "antidepressives, psychopharmacology, psychosis, schizophrenia, treatment",

author = "B. Galling and Vernon, {J. A.} and Pagsberg, {A. K.} and A. Wadhwa and E. Grudnikoff and Seidman, {A. J.} and M. Tsoy-Podosenin and M. Poyurovsky and Kane, {J. M.} and Correll, {C. U.}",

year = "2018",

doi = "10.1111/acps.12854",

language = "English",

volume = "137",

pages = "187--205",

journal = "Acta Psychiatrica Scandinavica",

issn = "0001-690X",

publisher = "Wiley",

number = "3",

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TY - JOUR

T1 - Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia

AU - Galling, B.

AU - Vernon, J. A.

AU - Pagsberg, A. K.

AU - Wadhwa, A.

AU - Grudnikoff, E.

AU - Seidman, A. J.

AU - Tsoy-Podosenin, M.

AU - Poyurovsky, M.

AU - Kane, J. M.

AU - Correll, C. U.

PY - 2018

Y1 - 2018

N2 - Objective: To evaluate the efficacy and safety of antidepressant augmentation of antipsychotics in schizophrenia. Methods: Systematic literature search (PubMed/MEDLINE/PsycINFO/Cochrane Library) from database inception until 10/10/2017 for randomized, double-blind, efficacy-focused trials comparing adjunctive antidepressants vs. placebo in schizophrenia. Results: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = −0.37, 95% confidence interval (CI) = −0.57 to −0.17, P < 0.001], driven by negative (SMD = −0.25, 95% CI = −0.44–0.06, P = 0.010), but not positive (P = 0.190) or general (P = 0.089) symptom reduction. Superiority regarding negative symptoms was confirmed in studies augmenting first-generation antipsychotics (FGAs) (SMD = −0.42, 95% CI = −0.77, −0.07, P = 0.019), but not second-generation antipsychotics (P = 0.144). Uniquely, superiority in total symptom reduction by NaSSAs (SMD = −0.71, 95% CI = −1.21, −0.20, P = 0.006) was not driven by negative (P = 0.438), but by positive symptom reduction (SMD = −0.43, 95% CI = −0.77, −0.09, P = 0.012). Antidepressants did not improve depressive symptoms more than placebo (P = 0.185). Except for more dry mouth [risk ratio (RR) = 1.57, 95% CI = 1.04–2.36, P = 0.03], antidepressant augmentation was not associated with more adverse events or all-cause/specific-cause discontinuation. Conclusions: For schizophrenia patients on stable antipsychotic treatment, adjunctive antidepressants are effective for total and particularly negative symptom reduction. However, effects are small-to-medium, differ across antidepressants, and negative symptom improvement seems restricted to the augmentation of FGAs.

AB - Objective: To evaluate the efficacy and safety of antidepressant augmentation of antipsychotics in schizophrenia. Methods: Systematic literature search (PubMed/MEDLINE/PsycINFO/Cochrane Library) from database inception until 10/10/2017 for randomized, double-blind, efficacy-focused trials comparing adjunctive antidepressants vs. placebo in schizophrenia. Results: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = −0.37, 95% confidence interval (CI) = −0.57 to −0.17, P < 0.001], driven by negative (SMD = −0.25, 95% CI = −0.44–0.06, P = 0.010), but not positive (P = 0.190) or general (P = 0.089) symptom reduction. Superiority regarding negative symptoms was confirmed in studies augmenting first-generation antipsychotics (FGAs) (SMD = −0.42, 95% CI = −0.77, −0.07, P = 0.019), but not second-generation antipsychotics (P = 0.144). Uniquely, superiority in total symptom reduction by NaSSAs (SMD = −0.71, 95% CI = −1.21, −0.20, P = 0.006) was not driven by negative (P = 0.438), but by positive symptom reduction (SMD = −0.43, 95% CI = −0.77, −0.09, P = 0.012). Antidepressants did not improve depressive symptoms more than placebo (P = 0.185). Except for more dry mouth [risk ratio (RR) = 1.57, 95% CI = 1.04–2.36, P = 0.03], antidepressant augmentation was not associated with more adverse events or all-cause/specific-cause discontinuation. Conclusions: For schizophrenia patients on stable antipsychotic treatment, adjunctive antidepressants are effective for total and particularly negative symptom reduction. However, effects are small-to-medium, differ across antidepressants, and negative symptom improvement seems restricted to the augmentation of FGAs.

KW - antidepressives

KW - psychopharmacology

KW - psychosis

KW - schizophrenia

KW - treatment

U2 - 10.1111/acps.12854

DO - 10.1111/acps.12854

M3 - Journal article

C2 - 29431197

AN - SCOPUS:85041965593

SN - 0001-690X

VL - 137

SP - 187

EP - 205

JO - Acta Psychiatrica Scandinavica

JF - Acta Psychiatrica Scandinavica

IS - 3

ER -

Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia

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Keywords

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