Will Decreased Noradrenergic Activity Normalize Information Processing in Patients With Schizophrenia?
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      The investigators want to try to improve information processing in schizophrenic patients via
      pharmacological intervention. The hypothesis is that decreased noradrenergic activity will
      normalize information processing (PPI, P50 gating, P300, and mismatch negativity) in patients
      with schizophrenia.
    

Detailed description: 
      A number of reports in literature provide evidence for, among others, an increased central
      noradrenergic activity in schizophrenia. In addition to this increased noradrenergic
      activity, patients with schizophrenia often show reduced filtering of sensory information,
      which is reflected in reduced P50 suppression and reduced prepulse inhibition of the startle
      reflex (PPI). In two separate initial studies in our laboratory, we found reduced sensory
      gating following administration of imipramine (a combined noradrenergic and serotonergic
      agonist) and desipramine (a highly specific noradrenergic agonist) to healthy volunteers.
      This provides evidence for a direct causal relation between the increased noradrenergic
      activity and the disturbed gating of sensory information, as both commonly found in patients
      with schizophrenia. Therefore, in a follow-up study, the effects of a noradrenergic
      antagonist will be investigated on the sensory gating of patients with schizophrenia. To
      further extend the data of our initial studies, the patients will additionally be tested for
      two psychophysiological parameters of attention that are usually found to be disturbed in
      patients with schizophrenia, i.e. mismatch negativity and selective attention. The design
      will conform to a double blind, placebo controlled experiment, in which either four doses
      (0.25 ug, 50 ug, 75 ug or 150 ug)of clonidine or placebo will be added to the current medical
      treatment of 20 male patients with schizophrenia on five occasions, separated by at least a
      week, after which they are tested in the Copenhagen Psychophysiological Test Battery
      (CPTB).In order to test the effects of clonidine in healthy volunteers, 20 healthy males will
      receive a fixed dose of 0.15 mg clonidine or placebo on two separate occasions separated by
      at least a week, after which they will be tested in the CPTB as well.
    

Intervention name(s): clonidine; clonidine
Intervention type(s): Drug; Drug
Intervention description(s): Either placebo or 25 ug, 50 uG 75 ug or 150 ug of clonidine will be added to the current medication of patients with schizophrenia, who are stable on their current medication; 0.15 mg of clonidine will be administered to 20 healthy male volunteers
Other intervention name(s): Catapressan; Catapressan
Intervention MeSH terms: Clonidine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Schizophrenia; Information processing; PPI; P50 gating; P300; mismatch negativity; clonidine