Modafinil Effects on Cognition in Schizophrenia Patients
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 4

Summary: 
      Patients with schizophrenia have problems in thinking, known as cognitive dysfunction. This
      includes many types of cognitive dysfunction, such as in attention, memory and language.
      These problems may explain why patients with schizophrenia think and act in unusual ways, and
      often have problems managing aspects of their lives that healthy adults take for granted.
      Unfortunately, the biochemical aspects of these dysfunctions are presently unknown, and it is
      not clear whether current psychiatric medications can improve these functions. A recent
      FDA-approved medication that may improve this function is modafinil. Studies in animals and
      healthy adults show that this medication can improve many of these cognitive functions. We
      plan to study the effects of modafinil on these cognitive processes, by giving various doses
      of this medication to patients before they perform tasks of these cognitive processes. We
      predict that when patients receive modafinil, they will perform better on a cognitive test,
      and that these benefits will depend on the dose given.
    

Detailed description: 
      Schizophrenia is a disorder of cognition. The cognitive deficits of schizophrenia are present
      at the onset of the disorder, prior to medication exposure, are persistent during periods of
      remission, and are strongly related to functional outcome. These deficits prominently include
      prefrontal cortex-dependent functions. While existing medications effectively treat psychotic
      symptoms, they exhibit modest benefit at best for cognitive dysfunction. Studies of cognition
      in animal models indicate that the neurotransmitter systems that mediate many cognitive
      processes are not generally augmented by existing antipsychotic medications. Therefore,
      advances in the treatment of schizophrenia will require the study of agents with novel
      pharmacological profiles to establish their potential to remediate cognitive dysfunction.

      This study will evaluate the effects of modafinil on the range of cognitive processes known
      to be disturbed in schizophrenia. Modafinil is an FDA-approved medication with a unique
      pharmacological profile and an increasing range of off-label indications. Its neurochemical
      effects in animal models include elevation of extracellular dopamine (DA), noradrenaline (NA)
      and glutamate in the neocortex. This profile is favorable for the enhancement of cognitive
      processes. These neurochemical effects also appear to be selective for cortical versus
      subcortical brain regions, suggesting that modafinil may have minimal effects on psychotic
      symptoms, or extrapyramidal, autonomic and hormonal side effects. In addition, it differs
      from amphetamine in structure, neurochemical profile and behavioral effects, with a lower
      risk of addictive or cerebrovascular effects. Recent studies in animal models, healthy adults
      and adults with psychiatric and neurological disorders indicate that modafinil improves
      prefrontal cognitive functions. This suggests that modafinil is a leading candidate for the
      treatment of cognitive dysfunction in schizophrenia. We aim to test modafinil effects on the
      remediation of deficits in cognition in individuals with schizophrenia. We will vary the dose
      within each participant to evaluate dose-response relationships, and directly compare
      cognition outcome measures for sensitivity to drug effects.
    

Intervention name(s): modafinil (M1, M2, M4)
Intervention type(s): Drug
Intervention description(s): modafinil 100, 200, and 400 mg oral dose
Other intervention name(s): Provigil
Intervention MeSH terms: Modafinil
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: cognition, pharmacology, memory, attention