This material was presented in the 25th European Congress of Psychiatry which was organised by the European Psychiatry Association in Florence, Italy from 1-4th April 2017. I had access to the material as I attended the full Congress. Please note that this material remains the intellectual property of the European Psychiatry Association and its authors and any citation should include a full reference to it. For more information on the EPA and how to become a member, please visit: http://www.europsy.net/

1. NEW HYPOTHESIS IN PHARMACOTHERAPY OF PSYCHOSIS,
THE EXAMPLE OF PARKINSON’S DISEASE PSYCHOSIS
Audrey FONTAINE, Univ. Lille, CHU LILLE, Department of Psychiatry, F-59000 Lille, France.
Greg RADU, Memorial University, Department of Psychiatry/ Saint-Clare’s Mercy Hospital, Saint John’s, Canada
With 10 million of pa/ents across the world, Parkinson’s disease is the second most common form of neurodegenera/ve disorder a=er
Alzheimer’s. Among half of pa/ents develop psycho/c symptoms, such as visual hallucina/ons and delusions. Emergence of psycho/c
symptoms complicates treatment, correlates with higher rates of placement in nursing home and in consequence severely affects quality
of life, making Parkinson’s disease psychosis (PDP) a major public health issue. The aim of this study is twofold: to iden/fy treatment
op/ons that could be used to treat PDP and clarify underlying pathophysiology
We conducted a literature review searching Pubmed, Google scholar and Cochrane library, using a combina/on of the following key words:
“Parkinson’s disease Psychosis” “visual hallucina/ons” “Pimavanserin” “Clozapine” “atypical an/psycho/cs”. A total of 120 ar/cles were
screened.
Defini;on of PDP
Occurring in up to 50% of pa/ents with Parkinson’s disease, it is
characterised by:
• Extracampine hallucina/ons (the sense of a presence or
flee/ng movement in the absence of an associated visual
percept)
• Illusions, pareidolias
• Simple or complex hallucina/ons, las/ng a few seconds to
a few minutes, par/cularly in evenings or low-s/mula/on
environments
• Delusions (mainly paranoid delusions of spouse infidelity)
Risk factors associated with the development of PDP
• Higher age at onset of motor symptoms
• Long follow-up /me
• Mild neurocogni/ve impairment or demen/a
• Significant motor impairment
• Poor quality of Life
• Depression
• Higher doses of dopaminergic drugs
• Rapid eye movement sleep Behaviour Disorder
• Visual impairment
Physiopathology: Mul/factorial
• Dopaminergic drugs induce hypersensi;sa;on of dopaminergic receptors in striatum, frontal and limbic structures, leading to
dysfunc/on of the limbic system and of the signalling pathways between frontal areas and associa/ve visual cortex, causing
hallucina/ons.
• Accumula/on of Lewy’s bodies in the amygdala, limbic, parietal and temporal structures leads to a neurotoxic cascade that
destroys dopaminergic neurons. Striato-nigral degenera/on causes desinhibi/on of interneurones, increase in cholinergic
ac/vity, and func/onal deficit of serotoninergic neurons, leading to a raise of 5HT2A & 5HT1A receptors. PDP emerges from an
imbalance between dopaminergic and serotoninergic systems.
• Illusions may be due to accumula;on of Lewy’s bodies in default mode network and due to dopaminergic and serotoninergic
dysfunc/on in thalamus and raphe nuclei, which are involved in the modula/on of visual input and sleep cycle regula/on.
Treatments
An/psycho/cs such as Risperidone, Olanzapine, Ziprasidone, Aripiprazole, and Que/apine may worsen motor symptoms, from
their ac/on on D2 receptors.
Clozapine, which inhibits 5HT2A and 5H1 receptors but has no ac/on on D2 receptors, has an/psycho/c effects with no
worsening of motor symptoms; but is associated with higher risk of agranulocytosis, myocardi/s, and requires close monitoring and
follow-up.
Pimavanserin, is a 5HT2A receptor inverse agonist without any dopaminergic ac;vity, approved in April 2016 by the FDA for
the treatment of PDP. The phase III mul/center, randomized, double-blind, parallel-group, placebo-controlled trial was performed by
Cummings &al in 2014. The 6 week study followed 199 adult pa/ents suffering from PDP. It showed a significant decrease in psycho;c
symptoms (using SAPS-PD, Scale for Assessment of Posi/ve Symptoms for Parkinson’s Disease) a=er 6 weeks of treatment with
Pimavanserin 40mg per day, with no major side effect reported. Yet, as Pimavanserin might prolong the QT intervals, it requires EKG prior
to use.
Studies combining Pimavanserin and atypical an/psycho/cs (ATP) have also been carried out, and showed fewer cases of
metabolic syndrome, hyper-prolac;nemia, and movement disorders, than treatment with an/psycho/c alone.
INTRODUCTION
METHOD
RESULTS
CONCLUSION
Serotonin inverse agonists turn out to have a significant an/-psycho/c effect without worsening motor symptoms, be well-tolerated, safe
and easy to use. Thus, they not only represent a major breakthrough in the pharmacotherapy of PDP, but they also point to the role of
serotoninergic dysfunc/on in psychosis. As a result, they might bring hope of new op/ons in the treatment of psycho/c disorders, that
could be efficacious and causing less metabolic and motor side effects.