Prucalopride and Cognition in Recovered Depression
Condition: Depression in Remission
MeSH terms: Depression; Depressive Disorder
Study type: Interventional

Summary: 
      The current study has two aims:

        1. To test the effect of 5-HT4 receptor agonism on cognition (including memory, attention
           and cognitive control) in individuals with previous history of depression.

        2. To explore if prucalopride has an effect on emotional processing biases consistent with
           its effects on serotonin.
    

Detailed description: 
      Cognitive impairment within depression is common and appears to be at least partly separate
      from the mood component. It is not well targeted by current treatments and it may persist
      even after remission of mood symptoms. Therefore, it may be clinically beneficial to search
      for new therapies that are able to improve cognition in those who have, or are recovering
      from, depression.

      Agonists of the serotonin receptor subtype 4 (5-HT4) have shown two profiles of effect in
      animal models: (i) a pro-cognitive profile, improving in learning and memory on a range of
      rodent paradigms; and (ii) an antidepressant-like profile, reducing depression and
      anxiety-related behaviours in rodent models of depression and anxiety.

      A previous study in our group examining acute prucalopride administration (1mg) in 40 healthy
      human volunteers found improvements in learning and memory but little effect on emotional
      processing. This pro-cognitive effect was supported by a subsequent study where healthy
      volunteers received 7 days of prucalopride. In this study, prucalopride led to both better
      performance on a visual memory task, and increased activation in the hippocampus and an
      associated memory processing region in response to a memory stimulus. As short-term treatment
      with clinically-effective antidepressants such as SSRIs is known to produce positive biases
      in the processing of emotional information in healthy volunteers, this lack of effect on
      emotional processing was not consistent with prucalopride having antidepressant potential,
      and is surprising considering the strength of the animal data. One factor that has not yet
      been explored is whether the translation was limited due to the low dose of prucalopride used
      in our previous study.

      Therefore, we wish to see if we (i) can translate this pro-cognitive effect of prucalopride
      into participants with a previous history of depression and current mild cognitive issues;
      and (ii) can use a full treatment dose of prucalopride to evaluate its effect on emotional
      processing.
    

Intervention name(s): Prucalopride; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 1mg prucalopride x 2d, 2mg prucalopride x 5-8d; Lactose / sucrose placebo
Other intervention name(s): Resolor; Montegrity; Axunio
Intervention MeSH terms: Prucalopride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Cognition; Emotional processing