Inflammation in patients with schizophrenia: the therapeutic benefits of risperidone plus add-on dextromethorphan.
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.


BACKGROUND
Protocol Record: HR-93-50;


BACKGROUND
NCT01189006; URL:                             http://www.clinicaltrials.gov.
Institute of Behavioral Medicine, Tainan, Taiwan.
Shiou-Lan
SL
Chen
Sheng-Yu
SY
Lee
Yun-Hsuan
YH
Chang
Shih-Heng
SH
Chen
Chun-Hsieh
CH
Chu
Nian-Sheng
NS
Tzeng
I-Hui
IH
Lee
Po-See
PS
Chen
Tzung Lieh
TL
Yeh
San-Yuan
SY
Huang
Yen-Kuang
YK
Yang
Ru-Band
RB
Lu
Jau-Shyong
JS
Hong
D000328:Adult; D003915:Dextromethorphan / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018967:Risperidone / Q000008:administration & dosage*; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome; D055815:Young Adult
D018836:Inflammation Mediators; D003915:Dextromethorphan; D018967:Risperidone