Pimavanserin (antipsychotic): indications, uses and side effects.

A drug that can especially help Parkinson's patients.

Psychotic symptoms do not only occur in psychotic disorders such as schizophrenia or delusional disorder. They also appear frequently in some dementias, such as Parkinson's dementia and Alzheimer's dementia.

Pimavanserin is a third-generation antipsychotic that in 2016 was approved for the treatment of psychoses in Parkinson's. Other effects it may have to treat symptoms such as agitation and depression in Alzheimer's, for example, are still being investigated.

In this article we will learn about its characteristics, mechanism of action, uses and adverse effects, as well as the results of clinical trials conducted with this recently appeared drug.

• Recommended article: "What is psychosis? Causes, symptoms and treatment".

Pimavanserin: what is it and how is it effective?

Pimavanserin is a recent antipsychotic, specifically an atypical antipsychotic, and is considered a third generation antipsychotic.. It is marketed under the name Nuplazid, and is synthesized by Acadia Pharmaceuticals laboratories.

It is a drug that has recently been found to alleviate psychotic symptoms in people with Alzheimer's disease without causing the usual side effects of other antipsychotics, such as the risk of relapse, stroke or death.

However, for the time being it has only been approved for use in treating psychosis in patients with Parkinson's dementia.

Parkinson's disease is a pathology that can end up developing dementia (and this happens in many cases); we usually know it by its motor symptoms (tremors, rigidity...), but in many cases of Parkinson's patients, psychotic symptoms also appear, such as delusions and/or hallucinations.

Studies carried out

This effect of Pimavanserin to treat psychotic symptoms in patients with Alzheimer's disease has been demonstrated in a study. In addition, another study (a clinical trial) conducted with pimavanserin showed how this drug was also effective in relieving psychotic symptoms in people with dementia caused by Parkinson's disease.

FDA approval

The latter finding allowed the FDA (U.S. government agency responsible for the regulation of drugs and other products) to approve pimavanserin for this indication in April 2016.

It should be noted, that the authorization of pimavanserin was based on the results of a single placebo-controlled trial, which lasted 6 weeks and involved 199 patients with Parkinson's disease, all of them with symptoms of hallucinations and/or delusions (psychotic symptoms).

Another relevant fact is that the patients who participated in the clinical trial with pimavanserin did not worsen their primary motor symptoms.

Innovative therapy

Pimavanserin has been designated a "breakthrough therapy" by the FDA.Thus, its approval as a treatment for psychosis in patients with Parkinson's dementia was logical.

The "breakthrough therapy" designation granted by the FDA is awarded to those drugs that, according to preliminary clinical evidence, can improve the symptoms of patients with serious diseases, and in a remarkable way.

Mechanism of action

On the other hand, Pimavanserin has a mechanism of action different from the usual one of classical antipsychotics; what it does is to block a specific serotonergic nerve receptor, the so-called THT2A or 5HT2A.

This receptor has been related to memory processes, cognitive functions and other organic functions; it is believed to play a mediating role in them.

Characteristics

As we have seen, pimavanserin is an atypical antipsychotic that is approved as an indication to treat psychotic symptoms associated with Parkinson's dementia (it is marketed under the name "Nuplazid").

In addition, A recent study has also found that pimavanserin may alleviate psychosis in patients with another type of dementia, Alzheimer's dementia, although research is ongoing and no conclusive statements or definitive conclusions can yet be drawn.Alzheimer's dementia, although research is still ongoing and no conclusive statements or definitive conclusions can yet be drawn. Specifically, what pimavanserin would do is reduce the frequency and intensity of psychotic symptoms in dementias (usually hallucinations and delusions).

Thus, pimavanserin is currently under development (under investigation) in relation to the possibility of treating possible cases of psychosis, schizophrenia, agitation and major depressive disorder in patients with dementia due to Alzheimer's disease.

Format and dosage

Pimavanserin is taken orally in tablet form. It is usually taken once a day; it can be taken with or without food. It is recommended that it be taken at the same time each day, as with other drugs.

Different from previous antipsychotics

As already mentioned, the mechanism of action of pimavanserin is different from the usual mechanism of action of antipsychotics, which block the D2 dopaminergic receptors in the brain (being dopaminergic antagonists).

In the case of pimavanserin, it is an inverse agonist and antagonist of serotonergic 5-HT2A receptors; it has a high binding affinity for them (it fits almost perfectly).

Pimavanserin is a well-tolerated and fairly safe antipsychotic, as shown by several clinical trials, conducted in the past few years.Pimavanserin is a well-tolerated and fairly safe antipsychotic, as shown by several clinical trials conducted prior to its commercialization.

Adverse effects

Regarding the adverse effects (AE) of pimavanserin, the aforementioned clinical trials showed how these were similar to those of the placebo condition.. Specifically, they were: a confusional state and peripheral edema. These adverse effects were found in at least 5% of patients in the trials.

An important caveat regarding the use of pimavanserin, and one that should be known, is that, like any antipsychotic, it can increase mortality in older (elderly) patients with psychotic symptoms related to their dementia. These are the adverse effects that appeared in clinical trials, but others are also associated, such as: Nausea and swelling (in hands, feet or ankles). As for the serious side effects of pimavanserin, the following are mentioned: hallucinations, rash, difficulty walking, confusion, hives, tightness in the throat, shortness of breath and swelling of the tongue.

It is important to see a doctor urgently in case of any of the last mentioned adverse effects.

Conclusions

Pimavanserin is a relatively recent drug with antipsychotic actions and has been shown to be effective in Parkinson's dementia to treat the associated psychosis. However, However, we must be cautious, since pimavanserin, although already marketed, is still under investigation..

On the other hand, although the symptoms we are most familiar with in Parkinson's patients are motor (and cognitive in the case of Alzheimer's), psychotic symptoms also appear in these pathologies, and with relative frequency. In addition, they cause considerable discomfort in these patients and in the people around them.

These symptoms interfere significantly in the daily functioning of these patients. That is why pimavanserin can be a promising drug that can help to improve the quality of life of these people, reducing their emotional deterioration and improving their psychological well-being.

Referencias bibliográficas:

• Ballard, C., Banister, C., Khan, Z., Cummings, J., Demos, G., Coate, B., et al. (2018). La pimavanserina, posible alternativa para aliviar la psicosis de la demencia. The Lancet Neurology, 17: 213-222.

• Kitten, A.K., Hallowell, S.A., Saklad, S.R., Evoy K.E. (2018). Pimavanserin: A Novel Drug Approved to Treat Parkinson's Disease Psychosis. Innov Clin Neurosci, 15(1-2): 16-22.

• MedLine Plus. (2019). Pimavanserina.