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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 4  |  Issue : 1  |  Page : 58-63

Psychotic symptoms in patients with Parkinson's disease: A case report and overview of management


Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication20-Jun-2017

Correspondence Address:
Sandeep Grover
Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jgmh.jgmh_43_16

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  Abstract 

Psychotic symptoms are not uncommon in patients with Parkinson's disease (PD). Several studies have evaluated the prevalence of psychotic symptoms in PD. Psychosis in PD can either occur independently or due to the effect of dopaminergic antiparkinsonian drugs or as a part of behavioral and psychological symptoms of dementia with PD. Often, it is difficult to manage psychosis in PD as there are very few pharmacological agents which can be used with relative safety. Effective management includes early identification of symptoms, ruling out other differential diagnoses, using appropriate psychopharmacological agents along with proper psychoeducation, and applying nonpharmacological strategies. In this report, we report the case of an 84-year-old woman with PD who developed dementia and psychosis during her illness and discuss the various challenges in managing psychosis in patients with PD.

Keywords: Antipsychotics, Parkinson's disease, psychosis


How to cite this article:
Sahoo S, Grover S. Psychotic symptoms in patients with Parkinson's disease: A case report and overview of management. J Geriatr Ment Health 2017;4:58-63

How to cite this URL:
Sahoo S, Grover S. Psychotic symptoms in patients with Parkinson's disease: A case report and overview of management. J Geriatr Ment Health [serial online] 2017 [cited 2019 Dec 15];4:58-63. Available from: http://www.jgmh.org/text.asp?2017/4/1/58/208609


  Introduction Top


Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, affecting about 1% of the elderly population worldwide.[1] Despite currently available treatment options, the disease lowers the quality of life to a great extent of person's suffering from the same.

Psychiatric manifestations are very common in patients with PD. Among the various psychiatric manifestations, management of psychosis is very challenging. Besides primary psychosis, 15%–40% of patients with PD experience hallucinations [2],[3] and 5%–10% patients experience delusions,[4],[5] which are either secondary to dopamine agonists or as a part of disease per se. Psychosis adds to the misery of patients with PD and affects their caregivers too.

Studies have reported that the two first-line antiparkinsonian drugs, dopamine agonists (such as pramipexole and ropinirole) and levodopa, to be associated with the development of psychotic symptoms in patients with PD.[1],[6],[7] Excessive stimulation or hypersensitivity of D2/D3 receptors in the mesocorticolimbic tracts, following administration of dopaminergic antiparkinsonian medication have been postulated to induce psychosis in PD.[6],[8]

Many a times, the symptoms are considered as part of normal aging process, and at times, clinicians do not ask specific questions to evaluate for the presence of psychotic symptoms. It has also been seen that many a times, clinicians fail to pick up minor psychotic symptoms such as vivid dreaming and illusions unless there is development of frank delusions and hallucinations, leading to delay in recognition and diagnosis of the same.[9] Psychosis in PD often poses great management challenge because of potentially catastrophic consequences for the patient and caregivers, lack of universally effective and safe drugs, and often progressive nature of this complication.

In this report, we present the case of an 84-year-old woman with PD who developed drug-induced psychosis and discuss the management aspects.


  Case Report Top


Mrs. X, 84-year-old widow, was admitted to the inpatient unit for the management of acute disturbances in the form of fearfulness and occasional confusion. Exploration of history revealed that patient has been suffering from PD for the last 3 years. She was started on tablet syndopa (carbidopa plus levodopa) 225 mg/day in divided doses after 1 year of onset of symptoms, with which within a month she had significant improvement in symptoms of PD and maintained improvement in motoric symptoms for the next 6–9 months. However, during this period, she developed cognitive symptoms in the form of forgetfulness of immediate and recent events, would forget names of family members, and would get confused in her own house and appear restless. She would complain of anxiety, epigastric discomfort during day time and had reduced sleep at night. About 3 months before admission to the inpatient unit in addition to her symptoms of PD and cognitive symptoms, she started to complaint of seeing her dead relatives and animals surrounding her bed in her clear consciousness and would become fearful and restless. She started to remain suspicious of her family members, would not allow anyone to come near her, and would voice that they were planning to kill her. She would be firm over her beliefs and would become agitated when anyone would try to explain her things to the contrary. In the period 3 months before admission, she also had worsening of her motoric symptoms. In view of her worsening condition, she was seen by a neurologist, and dose of tablet syndopa was gradually increased to 500 mg/day. After increase in the dose of syndopa, her psychotic symptoms worsened. She started to experience visual hallucinations (VHs) for the most part of the day and it became difficult to manage her at home. About 1 month before admission, in addition to the psychotic symptoms, she also started to remain disoriented, which would be more prominent during the evening time.

Family history revealed psychosis in two of her siblings.

General physical examination and systemic examination were within normal limits, except for the presence of resting tremors in both hands, rigidity in upper limbs, stopped posture, and festinating gait. On mental state examination, she was found to be anxious and had delusion of persecution and VHs. Mini mental state examination (MMSE) was 13/30.

Routine investigations which included complete blood count, biochemistry, liver function tests, and renal function tests were within normal limits, except for hyponatremia (serum sodium - 129 mmol/l). Magnetic resonance imaging of the brain revealed age-related cerebral atrophy.

A diagnosis of PD, dementia associated with PD, behavioral and psychological symptoms of dementia (BPSD) versus medication-induced psychosis with superimposed delirium was considered. Management included decreasing the dose of tablet syndopa to 375 mg/day in divided doses, addition of quetiapine 50 mg/day, correction of hyponatremia, and reorientation ques. With these interventions, initially, her delirium improved, she was oriented to time, place, and person, sleep improved, and there was no evening worsening of symptoms. Her MMSE improved to 21. However, psychotic symptoms persisted. In view of the disabling motoric symptoms of PD, syndopa could not be reduced further; hence, quetiapine was gradually increased to 100 mg/day with close monitoring of motoric symptoms. With quetiapine 100 mg/day, her psychotic symptoms resolved. At this stage, assessment of cognitive functions on PGI memory scale revealed that her memory was functioning at 28th percentile. In view of this, tablet memantine 5 mg/day was added. Family members were explained about the illness and were informed about the specific behavioral and cognitive interventions. She was discharged from the hospital after 1 month. She continued to be under follow-up treatment, and subsequently, her motoric and cognitive symptoms kept on worsening, for which syndopa was increased to 500 mg/day, memantine was increased to 10 mg/day, and pramipexole 2 mg/day was added. Tablet quetiapine was maintained at 150 mg/day during this period. Over the years, although her psychotic symptoms remained under control, her quality of life deteriorated significantly, due to the persistence of motor and cognitive symptoms.


  Discussion Top


Psychotic symptoms in patients with PD can have multiple etiologies. These may be an outcome of antiparkinsonian medications as part of Parkinson-plus syndrome (i.e., Lewy body dementia) or as part of BPSD associated with dementia in PD.

Psychotic symptoms are not considered as a primary symptom of idiopathic PD although some reports suggest the presence of psychosis in patients with PD.[10] Available evidence suggests that 15.8%–75% of patients with PD experience psychosis (or VHs). The wide variation in the prevalence rate is influenced by the study design, time frame under evaluation, and the assessment instrument. Among the various psychotic symptoms, VHs are considered to be the most common manifestations, with a prevalence of 16%–38%, followed by auditory hallucinations (prevalence: 0%–22%), delusions (prevalence: 1%–14%), and other minor psychotic symptoms (prevalence: 17.4%–72%). The risk factors identified in various studies for the development of psychotic symptoms in patients with PD include cognitive impairment (dementia, MMSE scores of ≤24, global cognitive impairment), higher age, lower age of onset of motor symptoms, longer duration of disease, history of depression or sleep disorder, modified Hoehn-Yahr stage of ≥4, postural instability, rapid progression of the motor component of the disease, more severe motor symptoms, receiving direct-acting dopamine receptor agonist, higher depressive score, comorbid affective disorders, daytime somnolence, worse visual acuity, positive family history of dementia, and presence of rapid eye movement sleep behavior disorders.[11]

The diagnostic criteria given by the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health (USA) for diagnosis of psychosis in PD suggests that the presence of at least one of the following: Illusions, false sense of presence, hallucinations, and/or delusions continuous or recurrent for at least 1 month and these symptoms should occur after the onset of PD and should not be caused by other disorders. Further, it specifies that it can occur with/without insight, dementia, and treatment for PD.[12] However, this last criterion is controversial as there is usually a clear relationship between the occurrence of psychotic symptoms and concurrent treatment with antiparkinsonian dopaminergic drugs.[13]

One thing to note in the index case was the type of hallucinations, i.e., VH which has been reported as the most common type of hallucinations in patients with PD presenting with psychosis.[13],[14] Classic VHs described in these patients are well formed, typically consisting of people (mostly familiar) and animals, which are mobile, lasting for brief duration and are usually chronic and repetitive in their content. These often develop in a parkinsonian patient with stable and constant antiparkinsonian treatment [13],[15] as was seen in the index case too. Many a times, it has been reported that VH often becomes familiar to the sufferer and he/she observes them with sympathy, without interacting with neutral emotions.[2],[16] The same pattern of VHs was noted in the index case too. VHs are also regarded as a herald symptom for dementia. Psychotic symptoms, more specifically VH in PD, have poor prognostic implications as they have been associated with increased risk of dementia [5] and mortality.[17],[18] Further, caregiver stress is markedly increased in PD patients with psychosis leading to increased rates of nursing home placements or hospitalization.

In the index case, psychotic symptoms followed emergence of cognitive symptoms in the background of PD. Hence, a possibility of BPSD was considered. However, there was worsening of psychotic symptoms and emergence of delirium with increase in the dose of syndopa. This association suggested that medications also possibly contributed to the worsening of psychosis and emergence of delirium. Although delirium resolved with reduction in dose of antiparkinsonian medication and low-dose quetiapine, psychosis did not subside completely. Increase in the dose of quetiapine led to resolution of psychosis. These associations suggested that possibly both the etiological factors contributed to development of psychosis. However, later, the patient could tolerate higher doses of antiparkinsonian medications under cover of quetiapine. Although final diagnostic possibility of BPSD was considered, this was not conclusive as contribution of medications could not be ruled completely.

Many studies focused on BPSD in dementia associated with PD have revealed that common BPSD symptoms are depression, apathy, anxiety, and hallucinations.[19],[20] Cluster analysis of these symptoms had resulted in identification of mainly five clusters, i.e., few and mild symptoms (irritability, disinhibition, aberrant motor behavior), mood symptoms, apathy, agitation, and psychosis.[21] These five clusters have been shown to be related with different aspects of dementia, in particular, psychosis/agitation was associated with caregiver distress, cognitive impairment, and parkinsonian signs.[19],[21] When compared with BPSD associated with Alzheimer's dementia (AD), studies have demonstrated that hallucinations were more severe in PD patients, while aberrant motor behavior, agitation, disinhibition, irritability, euphoria, and apathy were more severe in AD.[20] Similar BPSD symptoms, i.e., hallucinations, apathy, and irritability, were found in the index case.

Dementia in PD is very common with a cumulative incidence of dementia reported in a longitudinal study was 52% after 4 years and nearly 80% after 8 years.[22] One of the uniformly accepted risk factor for development of psychotic symptoms in patients with PD is dementia and this supports the association between PD with psychosis and diffuse Lewy body dementia (DLB). The phenomenology of hallucinations and delusions in the both disorders is almost same though often complex VH and well-systematized delusions are present in DLB.[23] The commonly used technique to distinguish between the two disorders if both have comorbid psychotic symptoms is to find out the time of onset of dementia. In patients with DLB, usually, the cognitive symptoms accompany or occur within 1 year of onset of motoric symptoms, whereas in patients with PD, cognitive symptoms usually follow motoric symptoms by a duration of more than 1 year [24] as was seen in the index case.

Management of psychosis in patients with PD is very challenging. Whenever a patient of PD presents with psychotic symptoms, a step-wise approach should be followed to rule out possible differential diagnoses. First step is to evaluate for delirium and to find out any possible association between psychosis and antiparkinsonian medications. Other differential diagnoses to be considered include Levy body dementia, Charles Bonnet syndrome, and BPSD as part of dementia [Table 1]. If all the differential diagnoses have been ruled out and the psychosis is thought to be possibly related to the use of antiparkinsonian medications, then efforts should be made to reduce and rationalize these medications.
Table 1: Differential diagnosis of Parkinson disease with psychosis

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Management of psychosis in patients with PD is very challenging. Management should follow a multidisciplinary approach with involvement of neurologist, psychiatrist, and other specialist depending on the need and the accompanying nonmotor symptoms of PD. If the psychosis is thought to be related to antiparkinsonian medications, efforts must be made to reduce the medications. In this regard, if the patient is on multiple antiparkinsonian agents, efforts should be made to reduce the drugs to the lowest effective dose, in the order of anticholinergics, selegiline, amantadine, dopamine receptor agonists, catechol-O-methyltransferase inhibitors, and finally, levodopa. However, if reduction in antiparkinsonian medications to the lowest dose tolerable without exacerbation of motor symptoms does not improve psychosis, use of antipsychotic medications is warranted.[8],[11]

Very few antipsychotics are regarded to be relatively safe in patients with PD. Use of antipsychotics carries a black box warning for increased mortality in patients with dementia. Hence, risk-benefit ratio has to be evaluated before starting any antipsychotic medication.

Few atypical antipsychotics such as clozapine, quetiapine, olanzapine, and risperidone have been evaluated for management of psychosis in patients with PD. Evidence for the management of psychosis in patients with PD with these antipsychotics is mainly in the form of open-label studies [26],[27],[28],[29],[30],[31],[32],[33],[34],[35] [Table 2]. However, over the years, there is evidence in the form of double-blind randomized control trials, comparing the antipsychotic medication with placebo or an active comparator group (references). Evidence from the data suggests that there is maximum beneficial effect of clozapine. A meta-analysis of studies concluded that among the atypical antipsychotics, only clozapine (Level B - considered effective) and quetiapine (Level C - may be considered effective) are considered to be beneficial.[62] However, the risk of agranulocytosis, orthostatic hypotension, somnolence, and strict hematological monitoring are the major limitations for use of clozapine in elderly individuals with PD. The second alternative is quetiapine, but use of quetiapine is also limited by narrow therapeutic window and hypersomnolence properties.[13] Quetiapine was used in the index case which resulted in the improvement in psychotic symptoms.
Table 2: Antipsychotics for treatment of Parkinson disease with psychosis

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To conclude, psychosis is very common in patients with PD. Management of psychosis in patients with PD requires proper evaluation to understand the association of psychosis with motoric symptoms, cognitive symptoms, and medications. Clinician's managing patients with PD should always carefully take history for presence of any kind of psychotic symptoms, and if these symptoms are suspected, more detailed evaluation in the hand of mental health professional is considered. In case the psychosis is related to medications, efforts must be made to reduce the dose of antiparkinsonian medications. However, it must be remembered that doses of antiparkinsonian medications must be reduced to the extent that this does not lead to worsening of motoric symptoms. If the management warrants the use of antipsychotics, these must be used in small doses and the patient must be monitored closely for the side effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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