Inflammation in Patients with Schizophrenia: The Therapeutic Benefits of Risperidone Plus Add-On Dextromethorphan

• Published in: Journal of neuroimmune pharmacology 2012-09, Vol.7 (3), p.656-664
• Main Authors: Chen, Shiou-Lan, Lee, Sheng-Yu, Chang, Yun-Hsuan, Chen, Shih-Heng, Chu, Chun-Hsieh, Tzeng, Nian-Sheng, Lee, I-Hui, Chen, Po-See, Yeh, Tzung Lieh, Huang, San-Yuan, Yang, Yen-Kuang, Lu, Ru-Band
• Format: Article
• Language: English
• Subjects: Adult; Antipsychotics; Biomedical and Life Sciences; Biomedicine; Brain-derived neurotrophic factor; Cell Biology; Clinical trials; Degeneration; Dextromethorphan; Dextromethorphan - administration & dosage; Double-Blind Method; Drug Therapy, Combination; Etiology; Female; Humans; Immunology; Inflammation; Inflammation - blood; Inflammation - drug therapy; Inflammation Mediators - blood; Male; Mental disorders; Middle Aged; Neuroleptics; Neurosciences; Original Article; Pharmacology/Toxicology; Plasma; Plasma levels; Risperidone; Risperidone - administration & dosage; Schizophrenia; Schizophrenia - blood; Schizophrenia - drug therapy; Schizophrenia - pathology; Toxicity; Treatment Outcome; Tumor necrosis factor-TNF; Virology; Young Adult
• ISSN: 1557-1890; 1557-1904
• DOI: 10.1007/s11481-012-9382-z

Increasing evidence suggests that inflammation contributes to the etiology and progression of schizophrenia. Molecules that initiate inflammation, such as virus- and toxin-induced cytokines, are implicated in neuronal degeneration and schizophrenia-like behavior. Using therapeutic agents with anti-inflammatory or neurotrophic effects may be beneficial for treating schizophrenia. One hundred healthy controls and 95 Han Chinese patients with schizophrenia were tested in this double-blind study. Their PANSS scores, plasma interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and brain-derived neurotrophic factor (BDNF) levels were measured before and after pharmacological treatment. Pretreatment, plasma levels of IL-1β and TNF-α were significantly higher in patients with schizophrenia than in controls, but plasma BDNF levels were significantly lower. Patients were treated with the atypical antipsychotic risperidone (Risp) only or with Risp+ dextromethorphan (DM). PANSS scores and plasma IL-1β levels significantly decreased, but plasma TNF-α and BDNF levels significantly increased after 11 weeks of Risp treatment. Patients in the Risp+ DM group showed a greater and earlier reduction of symptoms than did those in the Risp-only group. Moreover, Risp+ DM treatment attenuated Risp-induced plasma increases in TNF-α. Patients with schizophrenia had a high level of peripheral inflammation and a low level of peripheral BDNF. Long-term Risp treatment attenuated inflammation and potentiated the neurotrophic function but also produced a certain degree of toxicity. Risp+ DM was more beneficial and less toxic than Risp-only treatment. Clinical Trial Registration: Protocol Record: HR-93-50; Trial Registration number: NCT01189006; URL: http://www.clinicaltrials.gov