Add-On Therapy to Risperidonein Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Intervention name(s): Dextromethorphan
Intervention type(s): Drug
Intervention description(s): 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.
Intervention MeSH terms: Dextromethorphan
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment