Treatment of the Psychotic Symptoms of Parkinson’s Disease

Psychotic symptoms are common in persons with Parkinson’s disease.

Posted Apr 04, 2018

Parkinson’s disease (PD) is most often categorized as a movement disorder. Its most visible symptoms involve motor function:  a characteristic tremor, difficulty with gait, and trouble initiating movement. However, this illness often manifests a variety of other symptoms, including ones involving cognition and mood. Psychotic symptoms are often associated with PD as well.

Some individuals with PD develop a progressive dementia known as Lewy body dementia. Lewy bodies are abnormal accumulations of a protein called synuclein in the brain. In PD, synuclein initially accumulates in a brain region called the substantia nigra, but Lewy bodies can also accumulate in other brain regions, including cortical regions. The spread of Lewy bodies outside the substantia nigra is associated with non-motoric symptoms and the development of progressive dementia.

It is well known that psychotic symptoms commonly occur in individuals with Lewy body dementia. It is less appreciated that psychotic symptoms can also occur in PD in the absence of dementia. As PD progresses, so does the severity of psychotic symptoms. For example, individuals with PD may “see” a non-existent person or animal in the periphery of their vision. Initially, the person realizes that these images are not real. These are called passage hallucinations. Over time, a person with PD may see well-formed visual hallucinations but still realize that these visions are not real. As more time passes, and perhaps as the PD symptoms begin to overlap with symptoms of Lewy body dementia, the hallucinations seem more real to the person. Other types of psychotic symptoms such as auditory hallucinations and delusions may also develop.

Complicating this picture is the fact that psychotic symptoms can be a side effect of pharmacological treatments for PD. PD involves the destruction of dopamine-containing cells in the substantia nigra. The death of these cells leads to a state of dopamine deficiency. Many medications used to treat PD are designed to increase dopamine levels in the brain or mimic dopamine’s effects. However, these drugs can directly cause psychotic symptoms, and it is likely that they also exacerbate psychotic symptoms that are a result of the primary pathology of PD. When this occurs, the treating physician may try to minimize doses of current anti-PD drugs or switch to other anti-PD medications.

Medications used to treat psychotic symptoms in illnesses such as schizophrenia likely work by blocking dopamine receptors in the limbic regions of the brain. However, they can also block dopamine in brain regions related to movement such as the striatum and lead to abnormal movements including Parkinsonian-like symptoms. Therefore, drugs that may be able to ameliorate psychotic symptoms in persons with PD can make the motor symptoms of PD much worse.

In persons with PD, other concurrent medical conditions, such as urinary tract or respiratory infections, can lead to an acute confusional state known as a delirium, which can also increase the risk of psychotic symptoms. When treating psychotic symptoms in the context of PD, it is important to search for other medical conditions that may contribute to psychotic symptoms and to treat those conditions appropriately.  

Educating patients and their families is also important. Milder psychotic symptoms often aren’t frightening or dangerous. It can be helpful to explain to individuals with PD and their family members that these experiences are a result of PD and that it may be advisable to avoid antipsychotic drugs in order to prevent a worsening of motor symptoms.   

If pharmacologic treatment of psychotic symptoms is deemed necessary because of symptom severity, traditional antipsychotics are likely to make the movement symptoms much worse. One atypical antipsychotic drug, clozapine, can help psychotic symptoms without worsening movement symptoms. Clozapine is a truly unique medication. Although it is a powerful antipsychotic, it has minimal, if any, movement disorder side effects. Unfortunately, clozapine is a complex drug to use because it can cause marked decreases in certain types of blood cells, which must be monitored through routine blood testing. Clozapine also can have other side effects, including weight gain and sedation. 

Recently, a new medication has been approved for the treatment of psychotic symptoms in persons with PD. This drug, pimavanserin, is reported to decrease PD-associated psychotic symptoms without making motor symptoms worse. Apparently, this drug influences psychotic symptoms without directly blocking dopamine. Time will tell how effective and safe this agent will be. This drug is currently being tested in combination with traditional antipsychotics in persons with schizophrenia.

The presence of psychotic symptoms in individuals with PD presents a major treatment challenge because PD is caused by region-specific damage to the dopamine system and most medications used to treat psychotic symptoms work by blocking dopamine. New non-pharmacologic and pharmacologic approaches are being developed. Hopefully, these advances in treatment will help alleviate some of the discomfort and functional complications of PD.

This post was written by Eugene Rubin MD, PhD and Charles Zorumski MD.

References

Mathis, M.V., Muoio, B.M., Andreason, P., Avila, A.M., Farchione, T., Atrakchi, A., & Temple, R.J. (2017). The US Food and Drug Administration's perspective on the new antipsychotic pimavanserin. J Clin Psychiatry. 78(6):e688-e673.