Combination of clozapine and escitalopram in treatment of negative symptoms in residual schizophrenia

Residual schizophrenia is according to ICD 10 criteria, stage of chronic schizophrenia recurrence of positive symptoms in patients who have exhibited the full clinical state, and of general criteria for schizophrenia in the past. This stage is characterized by loss of interest, aimlessness, idleness, a self-absorbed attitude, and social withdrawal, and with absence of dementia or other organic brain disease or disorder, as well as chronic depression or institutionalism sufficient to explain the negative impairments. Antidepressant medication treatment has been associated with improvement in residual negative symptoms in patients with schizophrenia. Escitalopram is highly potent and highly selective serotonin reuptake inhibitor with highest affinity for the serotonin transporter (SERT). It's enantiomer R-citalopram counteracts to a certain degree the serotonin-enhancing action of escitalopram, and as a result, escitalopram is maybe, most potent SSRI antidepressant. Aim of this study was to investigate efficiency of the combined therapy with Clozapine and Escitalopram in treatment of negative symptoms in residual schizophrenia. Methods: this prospective clinical study included 78 patients with ICD 10 criteria for residual schizophrenia, who were randomly divided into 3 groups: control, Haloperidol group (H), N= 22; and two experimental groups: Clozapine (C), N=27; and Clozapine+Escitalopram (CE), N = 29. Patients were observed for 6 months in hospital and outpatient conditions, according to specially designed protocol, which included PANSS clinical score. Control group was treated with Haloperidole (5-15 mg/24 h), and experimental groups were treated with Clozapine (100-400 mg/24 h), and combination of Clozapine (100-400 mg/24 h) and Escitalopram (10-20mg/24 h). Results: there is no statistical significance in pretrial scores between groups for PANSS score, p = 0.829. There is no statistical significance in pretrial scores between groups for Negative PANSS, p=0.593. There is statistical significance in PANSS and Negative PANSS score reduction after 180 days in all three groups (p=0.000). After 180 days PANSS score was reduced in group H 7.9% (44.6-41.1), in group C 22.9% (45-34.7) and in group CE 31.4% (45.2-31). After 180 days Negative PANSS score was reduced in group H 8.2% (29.4.6-27), in group C 28.7% (30-21.4) and in group CE 39.6% (30.3-18.3). Results of PANSS reduction between all three groups are as follow: H vs. C, p = 0.000 after 180 days with high statistical significance; H vs. CE, p = 0.000 after 180 days with high statistical significance; C vs. CE, p = 0.000 after 180 days with high statistical significance. Results of Negative PANSS reduction between all three groups are as follow: H vs. C, p=0.000 after 180 days with high statistical significance; H vs. CE, p = 0.000 after 180 days with high statistical significance; C vs. CE, p = 0.000 after 180 days with high statistical significance. Conclusion: Combination of clozapine and escitalopram was found to be an effective treatment for negative symptoms in residual schizophrenia, with high statistical significance compared to monotherapy with haloperidol or clozapine.