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

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-tomedium,
differ across antidepressants, and negative symptom
improvement seems restricted to the augmentation of FGAs.