Objective: In this study, we assessed the efficacy of 2 pharmacodynamically different antidepressants, citalopram (a selective serotonin reuptake inhibitor) and reboxetine (a norepinephrine reuptake inhibitor), as adjunctive therapy to risperidone and olanzapine for the treatment of negative symptoms in schizophrenia. Method: We performed a 6-month, multicenter, double-blind, randomized, placebo-controlled clinical trial. The recruitment period was from November 2008 to December 2011. The sample comprised 90 patients with a diagnosis of schizophrenia (DSM-IV criteria) who exhibited negative symptoms. The patients were recruited from 10 centers in different cities of the Spanish State. The primary efficacy measure was change in score on the negative subscale of the Positive and Negative Syndrome Scale (PANSS) between baseline and 6-month assessment. Other efficacy measures were changes in the PANSS subscales and total score, as well as the Scale for the Assessment of Negative Symptoms (SANS) subscales and total score. Results: For statistical analysis, we employed mixed-effects models. We did not find statistically significant differences between the placebo group and the 2 treatment groups at 6-month assessments for the PANSS total (P = .6511), any PANSS subscale (negative [P = .5533], positive [P = .1723], or general psychopathology [P = .2083]), or the SANS (P = .5884). Cohen d measure showed a small effect size below the 0.5 threshold for all comparisons. Conclusions: In conclusion, our results do not support adjunctive use of citalopram or reboxetine with risperidone or olanzapine for the treatment of negative symptoms in schizophrenia. (C) Copyright 2014 Physicians Postgraduate Press, Inc.