NCT01189006

Add-On Therapy to Risperidonein Schizophrenia

A Double-blind, Placebo-Controlled, Randomized Study of the Efficacy of Dextromethorphan as Add-On Therapy to Risperidone Versus Risperidone Alone in Patients With Schizophrenia

• Status: Completed
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 161 (actual)
• Sponsor: National Cheng-Kung University Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

These results suggest that the DA neuroprotection provided by DM in the inflammation-related neurodegenerative models is not mediated through the NMDA receptor.

Detailed description

Liu et al. (2003) have reported that DM protected dopamine (DA) neurons against inflammation-mediated degeneration. Zhang et al.'s (2004) novel finding was that 1-10 μM DM protected DA neurons against LPS (10 ng/mL)-induced reduction of DA uptake functionally in rat primary mixed mesencephalic neuron-glia cultures. Morphologically, in lipopolysaccharide (LPS)-treated cultures, in addition to the reduction of abundance of DA neurons, the dendrites of the remaining DA neurons were significantly less elaborate than those of controls. In cultures pretreated with DM (10 μM) before LPS stimulation, DA neurons were significantly more numerous and the dendrites less affected. Significant neuroprotective was observed in cultures with DM added up to 60 minutes after the addition of LPS. Thus, DM significantly protects DA neurons not only with pretreatment but also with post-treatment (Zhang et al. 2004). The mechanism of the neuronprotective effect of DM is associated with the inhibition of microglia activation but not with its NMDA receptor antagonist property. Zhang et al. (2005) have examined several N-methyl-D-aspartate (NMDA) receptor antagonists, including MK801, AP5, and memantine. Results from these studies indicate that among these compounds tested there was no correlation between the affinity of NMDA receptor antagonist activity and potency of the neuroprotective on DA neurons. On the contrary, a better correlation was found between the anti-inflammatory potency and the neuron protection. These results suggest that the DA neuroprotection provided by DM in the inflammation-related neurodegenerative models is not mediated through the NMDA receptor. This conclusion is not in conflict with the previous reports, indicating that NMDA receptor blockade is associated with the neuroprotective effect of DM in acute glutamate-induced excitotoxicity models. The above evidences of benefit on auto-immune system with dextromethorphan would support that dextromethorphan as add-on therapy to atypical antipsychotics might be more effective than atypical antipsychotics alone on improvement of both positive and negative symptoms in schizophrenia.

Conditions

• Schizophrenia

Interventions

Type	Name	Description
DRUG	Dextromethorphan	Add-On double-blind study treatment commenced at randomization for 11 weeks while patients were continuing open-label risperidone. Randomization was immediately preceded by a one week open-label Risperidone-Only Treatment period. Patients who were receiving antipsychotics medication(s) at screen other than risperidone alone was withdrawn from previous non-risperidone medication(s) and at the same time commenced risperidone in titrating doses over a week. This Antipsychotic Switch-Over Period occurred between Screen and Risperidone-Only Treatment period. Patients remained hospitalized for at least during the Risperidone-Only treatment Period and first week of Add-On treatment Period.

Timeline

• Start date: 2005-01-01
• Primary completion: 2008-12-01
• Completion: 2008-12-01
• First posted: 2010-08-26
• Last updated: 2013-02-28

Locations

1 site across 1 country: Taiwan