Treatment of Refractory Schizophrenia With Riluzole
Condition: Schizophrenia; Schizoaffective
MeSH terms: Schizophrenia; Schizophrenia, Treatment-Resistant
Study type: Interventional

Summary: 
      The proposed study would evaluate the benefits of riluzole add-on treatment to patients with
      schizophrenia who are already receiving medications, but still experience symptoms.
      Neuroprotective medication riluzole is currently approved for treatment of amyotrophic
      lateral sclerosis (Lou Gehrig's disease), a severe neurological illness. Due to its unique
      mechanism of action, riluzole, if effective in helping the symptoms of schizophrenia, would
      open novel directions in treatment of schizophrenia.
    

Detailed description: 
      Schizophrenia is perhaps one of the most debilitating illnesses. Over the past years there
      has been limited improvement in the efficacy of the medications used to treat this disorder.
      In particular, the currently available antipsychotic drugs have small efficacy against
      negative symptoms and cognitive impairment associated with schizophrenia. This is critical
      considering that both negative symptoms and cognitive deficits contribute significantly to
      social and vocational impairment in schizophrenic patients. Furthermore, current treatment
      can not always provide satisfactory control of positive symptoms. While various extracellular
      neurotransmitter systems (dopamine, 5HT, GABA, etc. ) have been explored as targets for
      antipsychotic treatment, a substantial body of evidence suggests that neurodegenerative
      intracellular processes might be responsible for some of the symptoms of schizophrenia,
      resulting in cytopathic effects or inadequate cellular functioning. Some of these processes
      may be triggered by excitotoxic influence of neurotransmitters (i.e. glutamate). As many
      neuroleptic agents currently in use have some neuroprotective properties it is possible to
      speculate that medications with primarily neuroprotective mode of action might be of
      additional help in treatment of schizophrenia.

      Huntington's disease patients who in its advanced form exhibit some symptoms similar to that
      of psychotic illness, have, in a recent small (n=9) open label study with a neuroprotective
      drug riluzole, shown a temporary improvement in not only motor function, but also cognitive,
      and behavioral functioning (Seppi 2001).

      Based on all of the above, it seems possible to expect improvement in symptoms of
      schizophrenia with neuroprotective agents such as riluzole.

      Riluzole is the only effective medication approved for use in ALS (amyotrophic lateral
      sclerosis, Lou Gehrig's disease) which is one of the most severe and rapidly progressing
      neurodegenerative illnesses that affects motor neurons in the brain and spinal cord. A subset
      of ALS is inherited and involves more than 70 different mutations in the antioxidant enzyme
      superoxide dismutase (SOD) thereby contributing to reduced antioxidative defense against
      oxidative injury. This results in increased reactive oxygen species level in several
      organs/tissues while the bulk of symptomatology is related to degeneration in the subset of
      CNS neurons. Although riluzole is effective in both humans and the transgenic mouse model of
      familial ALS where it slows decrease in motor power, its exact neuroprotective mechanism of
      action is not known. Various studies suggest that riluzole might exert some of its beneficial
      effect by inhibition of glutamate release, inhibition of voltage-gated Na+ channels, but also
      intracellularly by inhibiting of protein kinase C (PKC), enzyme that was linked to oxidative
      neuronal injury. Although riluzole is generally well tolerated, side effects can occur and
      are mostly related to gastrointestinal problems, hepatotoxicity and asthenia.

      This 14 week study would evaluate the benefits of riluzole add-on treatment to patients with
      schizophrenia on neuroleptics with refractory symptoms.
    

Intervention name(s): Riluzole; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): placebo
Other intervention name(s): Rilutek
Intervention MeSH terms: Riluzole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment