Tackling Negative Symptoms in Male Patients with Schizophrenia Using a Norepinephrine Reuptake Inhibitor

Objective: Placebo-controlled trials of antidepressants in patients with schizophrenia with prominent negative symptoms usually have presented contradictory results. Reboxetine is a norepinephrine reuptake inhibitor (NRI) antidepressant. Preceding studies regarding possible advantageous effects of reboxetine on deficit symptoms of schizophrenia, too, have resulted in inconsistent outcomes. The present study again assesses the effectiveness of reboxetine as an adjunctive treatment in a group of patients with schizophrenia with prominent negative symptoms.

Method: Fifty male inpatients meeting the diagnosis of schizophrenia were enrolled into a 12-week parallel group, double-blind study with random assignment to reboxetine (n=25 patients) or placebo (n=25 patients). Inclusion criterion, in addition to the diagnosis of schizophrenia, was the existence of obvious negative symptoms for a duration of at least two years. Cases with existing co-morbidities like major depressive disorder or diagnosis of schizoaffective disorder or cases that were prescribed long-acting depot or atypical antipsychotics, antidepressants, or lithium were excluded. The Scale for Assessment of Negative Symptoms (SANS) was used as the primary outcome measure. Scale for Assessment of Positive Symptoms (SAPS), Simpson Angus Scale (SAS), Hamilton Rating Scale for Depression (HAM-D) and Mini-Mental Status Examination (MMSE) were used for comparison of the intervening parameters in this study. Duration of the assessment was twelve weeks, and the patients were assessed at baseline (week 0), and at the end of the 4th, 8th, and 12th week by SANS and SAPS. Treatment efficacy was analyzed by t test and repeated-measures analysis of variance (ANOVA). Statistical significance was defined as a 2-sided p value ≤0.05.

Results: According to our findings, 76% of the patients in the target group showed some positive response to reboxetine, in comparison with 24% in the control group (p<0.01). Mean total score of SANS in the reboxetine group decreased significantly from 79.94±1.20 to 74.23±4.07 (p<0.0001) at the end of the study, while such an improvement was not significant in the placebo group with a decrement from 80.42±2.46 to 79.08±5.83 (p<0.29). Between-group analysis, as well, showed that the mean total score of SANS in the reboxetine group, in comparison with the control group, improved significantly at 8 and 12 weeks (p<0.03 and p<0.01 respectively). Repeated-measures analysis of variance (ANOVA) showed significant improvement of SANS in the reboxetine group (p<0.02), and also a significant difference in this regard between groups (p<0.001). Changes of SAPS were insignificant in both groups. Effect size (ES) analysis for changes of SANS at the end of assessment indicated a large improvement with reboxetine (Cohen’s d = 2.91). Post-hoc power analysis showed a power equal to 0.53 (intermediary) for this trial.

Conclusion: Reboxetine, as adjuvant to haloperidol, may have helpful effects on negative symptoms of schizophrenia.