Antipsychotic Augmentation With L-Dopa

This study has been completed.
Information provided by (Responsible Party):
George Foussias, Centre for Addiction and Mental Health Identifier:
First received: July 5, 2012
Last updated: March 11, 2016
Last verified: March 2016

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.

Condition Intervention Phase
Drug: levodopa/carbidopa (generic version of Sinemet)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Augmentation of Antipsychotics With L-Dopa (Sinemet)

Resource links provided by NLM:

Further study details as provided by Centre for Addiction and Mental Health:

Primary Outcome Measures:
  • SANS - Schedule for the Assessment of Negative Symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • MATRICS-Consensus Cognitive Battery [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • BPRS - Brief Psychotic Rating Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • SAPS - Schedule for the Assessment of Positive Symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • NIMH-MATRICS Brief Negative Symptoms Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • CGI-S - Clinical Global Impression - Severity Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • QLS - Quality of Life Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • CDS - Calgary Depression Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • SAS - Simpson Angus Scale for Extrapyramidal Symptoms [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • BARS - Barnes Akathisia Rating Scales [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • AIMS - Abnormal Involuntary Movement Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • UKU - Udvalg for Kliniske Undersogelses [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Measures General Side Effects

  • LUNSERS - Liverpool University Neuroleptic Side-Effect Rating Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • BIS-11 - Barrett Impulsivity Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Y-BOCS - Yale-Brown Obsessive Compulsive Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • DAI - Drug Attitude Inventory [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • fMRI - Functional Magnetic Resonance Imaging [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Changes in Regional Brain Activity

  • SWN - Subjective Well-Being on Neuroleptics Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: September 2012
Study Completion Date: January 2016
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: L-Dopa (Sinemet)
Augmentation of current antipsychotic treatment with oral L-Dopa (levodopa/carbidopa) up to 900mg daily for 8 weeks
Drug: levodopa/carbidopa (generic version of Sinemet)
Oral levodopa 900mg daily as tolerated.
Other Names:
  • Levodopa/carbidopa
  • Sinemet

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.

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • SCID-confirmed (Structured Clinical Interview for DSM-IV Axis I Disorders) diagnosis of schizophrenia
  • ages 18-55

Exclusion Criteria:

  • history of substance abuse or dependence within 3 months; (ii) positive urine drug screen
  • history or evidence of any disorder that might adversely influence cognitive measures (e.g. mental retardation)
  • presence of serious neurological or general medical condition (e.g., Parkinson's disease, cardiac arrhythmia, epilepsy)
  • clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hematologic, hepatic, pulmonary (including bronchial asthma), or renal disease, narrow-angle glaucoma, malignant melanoma
  • pregnancy/nursing or women of child-bearing age not on regular contraceptive therapy (effects of L-dopa unknown)
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Please refer to this study by its identifier: NCT01636037

Canada, Ontario
Centre for Addiction and Mental Health
Toronto, Ontario, Canada, M5T 1R8
Sponsors and Collaborators
Centre for Addiction and Mental Health
Principal Investigator: Gary Remington, MD PhD FRCPC Centre for Addiction and Mental Health
  More Information

Additional Information:
Responsible Party: George Foussias, Sub-Investigator, Centre for Addiction and Mental Health Identifier: NCT01636037     History of Changes
Other Study ID Numbers: 156/2011 
Study First Received: July 5, 2012
Last Updated: March 11, 2016
Health Authority: Canada: Health Canada

Keywords provided by Centre for Addiction and Mental Health:
negative symptoms
deficit syndrome

Additional relevant MeSH terms:
Mental Disorders
Schizophrenia Spectrum and Other Psychotic Disorders
Antipsychotic Agents
Carbidopa, levodopa drug combination
Adjuvants, Immunologic
Anti-Dyskinesia Agents
Antiparkinson Agents
Aromatic Amino Acid Decarboxylase Inhibitors
Central Nervous System Depressants
Dopamine Agents
Dopamine Agonists
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Psychotropic Drugs
Tranquilizing Agents processed this record on May 25, 2016