Treatment Of Parkinson’s Psychosis

The Bottom Line On Pd Psychosis Treatments

While managing psychosis in Parkinsons can be challenging, what with trying to also like tremors and walking issues, there is hope. Not only can certain antipsychotic medications be effective, but the latest option, Nuplazid, is the first drug of its kind specifically approved for the treatment of psychosis in Parkinsons. Working with your health care team and caregivers can help you determine the best treatment plan to help reduce distressing psychosis symptoms.

• Parkinsons Information: National Institute of Health. Parkinsons Disease.

• Psychosis in Parkinsons Information: The Michael J. Fox Foundation for Parkinsons Research. Ask the MD: Parkinsons Disease Psychosis.

• Hallucinations and Delusions in Parkinsons: Parkinsons Foundation. Hallucinations/Delusions.

• A Guide to Psychosis in Parkinsons: American Parkinsons Disease Association. A Guide for Understanding Parkinsons Disease Psychosis Hallucinations and Delusions.

Treatment Of Parkinsons Disease Psychosis

Andrew Schleisman, PharmD Candidate 2017

Mikayla Spangler, PharmD, BCPSAssociate Professor of Pharmacy Practice

Emily Knezevich, PharmD, BCPS, CDEAssociate Professor of Pharmacy PracticeCreighton University School of Pharmacy and Health ProfessionsOmaha, Nebraska

US Pharm. 2016 41:HS20-HS26.

ABSTRACT: Delusions and hallucinations in patients with Parkinsons disease, a condition known as Parkinsons disease psychosis , have historically been treated with clozapine and quetiapine because of their relatively low likelihood of worsening motor symptoms. Although clozapine is considered the drug of choice, it is underused in this population because of the need for frequent monitoring. Quetiapine, on the other hand, is generally first-line treatment despite its questionable efficacy. Consequently, in 2006, the American Academy of Neurology identified a need for the development of a novel antipsychotic with evidence of both safety and efficacy in patients with PDP. Pimavanserin, which has shown promise in clinical trials, recently became the first agent to receive FDA approval for the treatment of PDP.

Implications For Clinical Practice And Future Research

In this review, quetiapine has not demonstrated statistically significant efficacy or tolerability, but is associated with troublesome side-effects and high drop-out rates. It is, however, important to note that these studies were small and that there is anecdotal evidence of efficacy. Quetiapine should therefore be used with caution. Olanzapine also requires caution due to an increased risk of parkinsonism and cerebrovascular accidents. Clozapine is associated with an antipsychotic effect. To facilitate its use clinically services need to be developed and integrated to ensure that patients can be appropriately followed-up and monitored. A retrospective chart review of a clozapine clinic for patients with Parkinson’s disease found a 66% response rate to clozapine.Reference Hack, Fayad, Monari, Akbar, Hardwick and Rodriguez30 However, there was a 41% retention rate to the service due to the inconvenience associated with frequent blood monitoring. Pimavanserin is novel treatment that warrants further investigation.

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Hallucinations And Delusions In Pd

Hallucinations and delusions are collectively referred to as psychosis.

Visual hallucinationsare the most common type of hallucination. In a visual hallucination, someone sees things that are not actually there. There can also be auditory and olfactory hallucinations. Often hallucinations are not alarming to the person experiencing them.

Delusions are when there is an alternative view of reality: an entire irrational story is created. Paranoia is a common type of delusion. Capgras delusions are a specific type of delusion where the person believes that a spouse, adult child, or other family member has been replaced by an imposter.

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What Causes Psychosis In Parkinsons

Currently, there is not a clear understanding of the exact cause of Parkinsons disease psychosis, although certain brain chemicals and receptors are believed to play a role. In general, the condition is believed to be caused by either one of the following:

Side effect of dopamine therapy:

Although an exact causal relationship has not been established, some believe that this condition may be a side effect of dopaminergic therapy .2Dopaminergic therapy increases dopamine levels, helping improve motor symptoms in patients with Parkinsons disease. However, increasing dopamine levels can also cause chemical and physical changes in the brain that inadvertently lead to symptoms such as hallucinations or delusions.

Natural outcome of the disease:

This condition can be triggered by changes in the brain that occur regardless of taking dopamine enhancing medication. Some of these changes occur naturally as Parkinsons disease progresses.2

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Medications With Proven Efficacy For Psychosis In Pd

In 1999, two studies independently showed clozapine to be superior to placebo for psychosis in PD . Some trials reported minor worsening of parkinsonism with clozapine , but others found improvement in motor signs . Expert consensus is that clozapine does not substantially worsen motor signs in PD. One study even suggested that clozapine may reduce mortality . However, along with various dose-related side effects, clozapine carries the risk of severe neutropenia in about 0.3%1.0% of patients, unrelated to dose . This risk is mitigated by weekly to monthly blood tests, but the frequent venipuncture and the coordination between prescriber, laboratory and pharmacy are difficult for many patients. In this population, clozapine is usually started at 6.25 at bedtime. Scheduled monitoring of neutrophil counts must be followed as per accepted guidelines . The final total daily dose of clozapine in PD psychosis typically ranges from 12.5mg to 150mg.

Beyond Parkinsons Dopamine Theory: Other Medications

There are some arguments against the dopamine theory of PDP. For example, in individuals with PD who undergo deep brain stimulation , some studies have demonstrated that psychosis emerges at similar rates in these PD patients as levodopa-treated PD patients.¹ The most convincing arguments, however, come from the actions of atypical, or second-generation, antipsychotics currently used to treat primary psychosis.

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Antipsychotics For The Management Of Psychosis In Parkinson’s Disease: Systematic Review And Meta

Published online by Cambridge University Press: 02 January 2018

CT1 SHO in General Medicine, Nottingham University Hospitals NHS Trust, Queen’s Medical Centre, Nottingham, UK

Oluwademilade A. Onalaja

Stratford Healthcare, Arden Street, Stratford-Upon-Avon, UK

*

Antipsychotics can exacerbate motor symptoms in Parkinson’s disease psychosis.

To systematically review the literature on the efficacy and acceptability of antipsychotics for Parkinson’s disease psychosis.

Randomised controlled trials comparing an antipsychotic with placebo were systematically reviewed.

The final selection list included nine studies using quetiapine , clozapine , olanzapine and pimavanserin . A narrative synthesis and meta-analyses were presented for each antipsychotic. Clozapine demonstrated superiority over placebo in reducing psychotic symptoms. Quetiapine and olanzapine did not significantly improve psychotic symptoms. All three antipsychotics may exacerbate motor symptoms. Quetiapine studies were associated with high drop-out rates due to adverse events. Pimavanserin is a novel treatment that warrants further investigation.

Further research is needed. Clozapine and pimavanserin appear to be a promising treatment for Parkinson’s disease psychosis.

Parkinsons Disease And Initial Motor Symptoms

What has been assumed to be primarily a dopamine deficiency in PD is better viewed as a disruption of multiple monoaminergic systems, with dopamine disruption dominating the motor symptoms and serotonin taking a dominant position in Parkinsons disease psychosis .

The classic tale of neurodegeneration in Parkinsons begins with the loss of 50% to 80% of nigral neurons. This stage is when the first traditional motor symptoms appear .

As early motor symptoms become unmanageable, patients are often prescribed levodopa and carbidopa to help restore the dopaminergic tone of the nigrostriatal pathway.

• Levodopa is a dopamine precursor, as likely to be metabolized outside the brain as inside.

• Carbidopa, and other enzyme inhibitors , delay the conversion of levodopa, allowing more of it to pass the blood-brain-barrier for conversion in the brain.

Once in the brain, the exogenous dopamine is used just like the endogenous neurotransmitter, not only resupplying the nigrostriatal pathway and reducing motor symptoms but affecting other residential monoaminergic systems, especially those involved in PDP.

While individuals with late-onset Parkinsons are more susceptible to developing psychotic symptoms, PDP in younger patients can emerge acutely and is associated with concurrent Lewy body dementia.²

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Managing Psychosis In Parkinson Disease: Challenges And Opportunities

Erica Slaughter, MSNeurologyLive

Although the indication of pimavanserin has provided some relief, more work remains to improve how physicians diagnose, treat, and manage psychosis symptoms.

Rajesh Pahwa, MD

Neuropsychiatric manifestations represent a core feature of Parkinson disease , from the prediagnostic phase to end-stage disease. Parkinson disease psychosis is thought to be a result of an increase in the numbers of 5-HT2A receptors and dopaminergic hyperactivity. However, dopamine agonist medications like levodopa that help reduce muscle rigidity and tremors can also trigger psychosis, marked by hallucinations and delusions. The clinical approach for treating PDP traditionally relies on initially reducing the dopaminergic agent and considering an add-on therapy for psychiatric symptom management.

Definition and formal criteria for PDP as a distinct disease entity have been established. PDP symptoms are believed to progress and can include hallucinations involving all 5 senses , illusions, and delusions. The progression is such that symptoms that are merely bothersome at an early stage will likely become more severe, varied, and troublesome as the disease progresses. PDP and impulse control disorders are reported to be associated with DA intake3 and are included in the behavioral spectrum of nonmotor symptoms of PD.

Poorly Tolerated Or Unproven Treatments

Until recently, the only available treatments for psychosis consisted of reducing dopaminergic tone. At its extreme, this consisted of removing all antiparkinsonian medications for a period of time, a so-called drug holiday. As Friedman observed, however, this was not a holiday in the usual sense, since motor function quickly worsened . In fact, patients could develop a neuroleptic malignant syndromelike presentation, which occasionally could be lethal. Dopamine D2-like receptor antagonists prior to the 1990s all had unacceptable motor side effects.

In the 1990s and 2000s, newer antipsychotics were tried eagerly in PD psychosis in hopes of better tolerability . Like their predecessors, they block dopamine at D2-like receptors, but have more complex pharmacology, often including serotonin 5HT2 receptor antagonism or lower affinity for striatal D2Rs, and cause fewer motor side effects in patients with schizophrenia . Small, open trials with remoxipride and zotepine generally seemed positive, but several patients experienced intolerable motor side effects . Risperidone at low dose showed some promise in early reports , but intolerable motor side effects in others . In the only controlled trial with risperidone in PD, it was more effective than clozapine but less well tolerated . In controlled trials, olanzapine proved superior to placebo for PD psychosis , but worsened motor function .

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What Happens In Pdd

People with PDD may have trouble focusing, remembering things or making sound judgments. They may develop depression, anxiety or irritability. They may also hallucinate and see people, objects or animals that are not there. Sleep disturbances are common in PDD and can include difficulties with sleep/wake cycle or REM behavior disorder, which involves acting out dreams.

PDD is a disease that changes with time. A person with PDD can live many years with the disease. Research suggests that a person with PDD may live an average of 57 years with the disease, although this can vary from person to person.

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Clinical Presentation And Cases

The National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke sponsored a workshop on PDP, and provisional diagnostic criteria were published in 2007 . It is important for providers to recognize the clinical spectrum of symptoms associated with PDP. Symptoms will range from mild visual distortions and the sense of a presence to fully formed, complex hallucinations to delusions . The most common type of complex hallucinations is visual, although other sensory modalities may be affected. Auditory hallucinations have been reported in 8% of patients with PDP, but predominant auditory symptoms are uncommon. Hallucinations may initially be nondisruptive, such as seeing ants on the floor or hearing music. Patients may report such hallucinations are not disturbing and may be interesting or even entertaining. Because these types of hallucinations are not disruptive, patients may not be as likely to report their occurrence to caregivers or clinicians. Over time, and with the progression of PD, the nondisruptive quality of hallucinations tends to diminish and is replaced by an alarming or more malignant quality that disrupts daily activities.

TABLE

National Institute of Neurological Disorders and StrokeNational Institute of Mental Health provisional diagnostic criteria for Parkinson disease psychosisa

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Attitudes Of Care Partners Toward Medications For Parkinsons Disease Psychosis

S. Mantri, S. Albert, E. Klawson, L. Alzyoud, M. Daeschler, C. Kopil, C. Marras, L. Chahine

Category:Parkinsons Disease: Psychiatric Manifestations

Objective: To explore attitudes regarding use of medications among care partners of individuals with Parkinsons disease psychosis.

Background: Parkinsons disease psychosis is a highly morbid manifestation of PD and negatively impacts the quality of life of both patients and their care partners . Effective therapies for PD psychosis exist, but some carry significant risk. Understanding CP attitudes regarding medications for PD psychosis could help inform healthcare provider discussions and promote shared decision-making regarding their use.

Method: This was a mixed-methods study. Prompted online journaling activities and structured telephone interviews were conducted with CPs of patients with PD psychosis, identified via Fox Trial Finder. Using common themes from journaling and telephone interviews, a survey was then developed and administered to caregivers of PD patients participating in the online study Fox Insight. The survey included the Neuropsychiatric Inventory , Caregiver Burden Inventory , and a multiple-choice questionnaire regarding attitudes on medications.

To cite this abstract in AMA style:

Mov Disord.

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What Are Parkinsons Delusions

Delusions are thoughts that arent grounded in reality. Theyre not as common as hallucinations, affecting only about 8 percent of people with Parkinsons disease. But they are harder to treat.

The most common delusions involve paranoia for example, the feeling that people are out to get you, or that your partner is cheating on you. Having these thoughts can lead to aggressive or even dangerous behavior.

Youll start with a visit to your doctor for an evaluation. Your doctor may diagnose you with this condition if you:

• have had symptoms like hallucinations and delusions for at least 1 month
• dont have another condition that could be causing these symptoms, like dementia, delirium, major depression, or schizophrenia

Not everyone with Parkinsons disease will develop psychosis. Youre more likely to have this if you:

There are two possible causes of Parkinsons psychosis:

• changes in levels of brain chemicals like serotonin and dopamine from the disease itself
• changes in levels of these chemicals from medications that treat Parkinsons disease

Dopamine is a chemical that helps your body move smoothly. People with Parkinsons disease have lower than normal levels of dopamine, which causes their body to move stiffly.

Drugs that treat Parkinsons improve movement by increasing dopamine levels. Yet they can sometimes cause psychosis as a side effect.

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Levodopa And Motor Symptoms

The development of psychosis in people with Parkinsons disease is thought to stem from levodopa treatment, in the same way that dyskinesias and the abrupt on-off episodes appear to be motor complications also of levodopa medications. Because PD is neurodegenerative- meaning the nigrostriatal pathway will continue to degenerate- patients are put on higher and higher doses of levodopa. With higher doses and degenerating nigrostriatal pathway, the extra dopamine floods the brain causing unregulated and nonspecific exposure within vast areas of the brain. This surplus dopamine is seen as the source of both motor and non-motor complications.

The unregulated exposure to dopamine in the striatum that is, the presence of dopamine which is not a result of stimulated vesicular release by the activity of neurons in the nigrostriatal pathway- by striatal D2 receptors is associated with unfettered stimulation of the motor neurocircuitry. This notion is supported by the evidence from people with PD who underwent striatal mesenchymal stem cell transplantations which provide a specific but unregulated release of dopamine, and who still develop dyskinesia, despite the reduction and sometimes termination of levodopa therapy.

Tips For Living With Hallucinations

It is important for people with PD to talk about hallucinations with their family and care team these are manageable and can be troublesome if not treated. Discuss all possible symptoms with your doctor, no matter how minor, rare or bizarre you may think they are.

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Features Of Parkinson’s Disease Psychosis

PDP typically arises later in the course of the disease, approximately 10 years after initial diagnosis of PD. Symptoms typically arise in the context of retained insight and clear sensorium . Over time, symptoms such as visual hallucinations or delusions tend to recur and progress and insight is lost. Prominent hallucinations early in the course of the disease may suggest Lewy body dementia, Alzheimer’s disease, or a preexisting psychiatric disorder .

Treatment Options For Parkinsons Disease Psychosis

Psychosis in PD is a serious medical concern. A properly trained physician, such as a neurologist or psychiatrist, should be in charge of treating it. Once the physician has confirmed Parkinsons psychosis, they will begin treatment.

One MyParkinsonsTeam member mentioned, Please make sure your doctor knows about your hallucinations. They do have medicines for them.

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What Is Parkinsons Disease Psychosis

Hallucinations and delusions are the most common symptoms of Parkinsons psychosis. Hallucinations involve a person seeing, hearing, feeling, smelling, or tasting something that isnt really present. Most hallucinations in PD psychosis are visual, where someone sees a person or an animal.

Delusions are ongoing thoughts that are not based in the real world. A person with delusions does not intentionally try to have these thoughts. These may include being jealous, feeling persecuted, or fixating on ones own body or health.

When describing their first hallucination, one MyParkinsonsTeam member said, In my living room I saw a little boy covered in fur. Lasted a good eight seconds, vivid and defined. I wasnt startled, just curious and absolutely believed it was real until it vanished.

Learn more about recognizing hallucinations and delusions.