Antipsychotic Augmentation With L-Dopa
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 2

Summary: 
      Dopamine, a chemical in the brain, has been linked to schizophrenia for a number of years.
      More recently, there is evidence that certain areas affected in schizophrenia (e.g.
      motivation, cognition) may reflect too little dopamine, whereas symptoms like hallucinations
      and delusions have been linked to too much dopamine.

      This study is designed to evaluate the safety, tolerability, and efficacy of giving L-dopa
      (Sinemet) to see if it will improve those symptoms related to too little dopamine. L-dopa has
      been approved for other medical conditions (e.g. Parkinson's disease) and works to increase
      levels of dopamine.

      The investigators are linking this study with neuroimaging (fMRI) which will allows us to
      link any changes the investigators might find in clinical symptoms with changes in the brain.
      This information can prove useful in better understanding the mechanisms that account for
      these symptoms, as well as possible new treatments.

      At present , treatments for these other symptoms that seem important in functional measures
      of outcome (i.e. deficit symptoms, including amotivation; cognitive symptoms) in
      schizophrenia have not proven particularly effective. It is hoped that L-dopa may provide a
      treatment that is more effective; going forward, this information would also be useful in
      drug development and future lines of investigation.

        1. L-dopa will prove effective in improving deficit (also called 'primary negative' e.g.
           amotivation) and cognitive symptoms in schizophrenia.

        2. It will be well tolerated and not increase risk of psychotic symptoms when administered
           in conjunction with their regular antipsychotic medications.
    

Detailed description: 
      Pharmacological (and non-pharmacological) strategies that may significantly improve the
      negative and cognitive symptoms of schizophrenia represent a critical unmet therapeutic need.
      There is wide acceptance of the notion that both negative and cognitive symptoms are best
      understood as features of hypo- rather than hyperdopaminergic activity. The primary negative
      and cognitive symptoms appear central to schizophrenia and predate the neurodevelopmental
      changes that subsequently give rise to the hyperdopaminergic state underlying positive
      symptoms. In using L-Dopa specifically, we avoid the abuse potential of agents such as the
      psychostimulants, or perturbations in pharmacological action as a function of dose, as
      observed with dopamine agonists. Further, more recent neuroimaging studies have provided in
      vivo evidence in keeping with the underlying rationale. First, imaging studies have
      demonstrated that L-dopa induces shifts in activity in both cortical and subcortical
      structures linked to reward, affect and cognition. Along similar lines, L-dopa-induced
      changes have been associated with improvement in motivation, cognitive tasks, and affect.
    

Intervention name(s): levodopa/carbidopa (generic version of Sinemet)
Intervention type(s): Drug
Intervention description(s): Oral levodopa 900mg daily as tolerated.
Other intervention name(s): Levodopa/carbidopa; Sinemet
Intervention MeSH terms: Levodopa; Carbidopa; Carbidopa, levodopa drug combination
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: schizophrenia; negative symptoms; deficit syndrome; SANS; Sinemet; L-dopa; levodopa; carbidopa; augmentation; antipsychotics