Adjuvant Therapy With Pergolide in Treating Cognitive Deficits in Schizophrenia
Condition: Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional

Summary: 
      The objective of this study is to compare the modulation of pergolide, a D1/D2 receptor
      agonist, to placebo in non-acute schizophrenic subjects under concomitant therapy with
      atypical antipsychotics on specific PFC functions. Further aims are to assess the influence
      of pergolide on psychopathology and extrapyramidal symptoms in comparison to placebo.
    

Detailed description: 
      Additionally to the desired treatment of positive symptoms, the administration of typical
      neuroleptics can lead to undesired side effects such as increase of negative symptomatic and
      cognitive deficits. The influence of atypical neuroleptics on cognition is still not very
      well studied. Furthermore there is evidence that some cognitive symptoms seen in
      schizophrenia are related to a disturbance in the prefrontal cortex PFC and involve specific
      subtypes of dopamine receptors, namely D1 subtypes, which predominates in this area. It is
      assumed that patients with this spectrum of cognitive deficits have the worse course and
      prognosis. Furthermore these deficits are more therapy resistant to the conventional current
      therapy approaches. There is however some evidence pointing to a positive influence of
      dopamine agonists on these deficits, but the selective effect of dopamine sub-receptors is
      still not well investigated. The aim of the study is to examine whether cognitive deficits in
      higher cognitive functions of the PFC such as working memory, semantic association and
      executive control improves under dopamine agonistic therapy in schizophrenia and whether this
      is related to selective D1 modulation.

      We predict that the modulation of D1 subtype receptors improve performance in each of these
      tasks. Because there is no D1 agonist available for human research we decided to use a design
      comparing a dopamine agonist with mixed D1 and D2 agonistic properties (pergolide) to placebo
      under a stable D2 antagonistic continuous-therapy with atypical antipsychotics. With this
      design the D2-component of pergolide can be antagonized by the atypical antipsychotics and a
      D1 agonistic effect can be suggested, as well as protecting patients against a psychotic
      re-exacerbation. With this study we aim to bring more insight in the therapy of PFC cognitive
      deficits of schizophrenia by helping to elucidate the role of selective agonists on cognition
      in schizophrenic patients. I
    

Intervention name(s): Pergolide
Intervention type(s): Drug
Intervention description(s): 0,3 mg pergolide (the first two days begin with 0,05mg, then increase of dose of 0,1mg every 3 days for a maximum of 0,3mg/d, taken orally 3x 0,1mg/day). Then stable dose of 0,3mg for one week.. Subsequently slow (for 8 days) reduction of dosage of 0,1mg every 3 days for 6 days then 0,05mg every day for the last two days.
Placebo group is identical in appearance and number of placebo capsules, in the same starting and maintenance scheme as for the pergolide group.
Other intervention name(s): Parkotil; Pergolid
Intervention MeSH terms: Pergolide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: schizophrenia; cognitive deficits; dopamine; dopamine agonists; prefrontal cortex; D1 specific modulation; pergolide; executive control; working memory; Influence of pergolide on cognition in Schizophrenia; D1-specific modulation of prefrontal functions; Influence of pergolide on psychopathology and depression; Influence of pergolide on extrapyramidal symptoms