There has been a critical unmet need for better drugs in order to address hallucinations and psychosis in Parkinson's disease. Typically we choose quetiapine (seroquel) or clozapine (clozaril) instead of the classical dopamine blocking drugs for treatment of psychosis associated with Parkinson's disease. The classical drugs tend to worsen the motor symptoms of Parkinson's disease. Pimavanserin is a new drug that works without blocking the dopamine receptor.
Here are the tips about what you need to know about Pimavanserin for treatment of Parkinson's disease related psychosis.
- Though classically we think about the dopamine receptor in Parkinson's disease as underpinning psychosis symptoms, serotonin has also been implicated
- Lysergic acid diethylamide and phencyclidine (PCP) seem to stimulate 5HT2A serotonin type of receptors. Stimulation of these receptors may lead to hallucinations.
- Most available antipsychotic drugs block the 5HT2A receptor and the D2 dopamine receptor
- It is possible that the 5HT2A blocking mechanisms of newer antipsychotics may underpin their benefit with low side effect portfolio
- Pimavanserin is a 5HT2A inverse agonist (binds to the same receptor as an agonist; an agonist would stimulate the receptor, but an inverse agonist would do the opposite and reduce stimulation below basal levels at that particular brain receptor)
- Pimavanserin is not thought to have motor side effects (i.e. tardive dyskinesia, parkinsonism)
- The emerging safety profile has shown it is superior to other available antipsychotics
- There is one Phase III trial that has shown benefit
- The company is planning to pursue FDA approval for Parkinson's disease (it has been previously more used in Schizophrenia)
It is possible that Pimavanserin will be another great alternative for some patients with Parkinson's disease, especially since it does not worsen motor symptoms. One also wonders if in severe cases it could be added on to seroquel or clozaril to improve treatment of difficult to control hallucinations and psychosis.