A Case of Visual Hallucinations and Parkinsonian Symptoms
Mr. P is a 69-year-old male with a 7-8-year history of parkinsonian motor symptoms and visual hallucinations. He was first referred to a local mental health clinic 3 years ago, and at that time described seeing transparent human figures walking around his house. He said that these visual hallucinations have become more vivid and now occur on a daily basis. The patient also complained of some difficulty with his memory. Cognitive impairment was noted at his initial presentation. He was unable to draw a clock face, complete a serial 7’s task, or perform simple calculations. Over time, Mr. P’s hallucinations worsened, and he developed paranoid ideation. He displayed episodes of acting out aggressively in response to his psychotic symptoms. Over the previous 3 years, he had required multiple hospitalizations related to his psychosis and agitation.
Multiple attempts had been made to address the patient’s cognitive impairment and visual hallucinations without causing further impairment in motor function. He was treated with rivastigmine 6 mg twice daily for dementia, which he tolerated well; however, his psychosis persisted. Trials of neuroleptic medications, including olanzapine and ziprasidone, did not alleviate the patient’s psychosis, and resulted in worsening parkinsonian symptoms. Mr. P was unable to tolerate quetiapine due to significant orthostatic hypotension. The patient had been taking carbidopa/levodopa to address his parkinsonian symptoms. Attempts to decrease the dose of this medication were also made in case it had been exacerbating his psychosis. Despite these efforts, Mr. P’s psychosis became more severe. His visual hallucinations persisted, and his delusions worsened. He developed ideas that he was going to be harmed, and frequently would act out violently toward others due to his paranoia. He decompensated further to the point that he was no longer oriented at all, and his oral intake decreased dramatically. Mr. P could no longer ambulate due to impaired mobility and severe orthostasis. He required assistance with all activities of daily living.
He was admitted to the hospital for evaluation and management. Mental status exam revealed a thin, unkempt man lying in bed, wearing a vest restraint for his own safety. Mr. P was cooperative but made minimal eye contact, staring straight ahead. An upper-extremity tremor was apparent and more prominent on his right side. His speech was soft, with latency of response, and some unintelligible words were noted. Mr. P endorsed a euthymic mood. His affect was flat. He denied any suicidal thoughts. He described delusions, such as currently being a prisoner of war, and paranoia regarding the intent of others to harm him. He admitted to visual hallucinations of figures in his room, but denied auditory hallucinations. He was oriented to person only. His insight and judgment were significantly impaired. It was determined that Mr. P met the clinical criteria for dementia with Lewy bodies (DLB) due to features of cognitive decline, episodes of fluctuating cognition, recurrent visual hallucinations, and motor features typical of Parkinson’s disease. The patient’s Parkinson’s disease medications, which at this time included carbidopa/levodopa and pergolide, were eventually discontinued due to poor response and the ongoing risk of exacerbating his psychotic symptoms. A urinary tract infection was found on admission, but no improvement was noted in Mr. P’s mental status following treatment. No other medical causes were found that could explain his rather rapid deterioration. Quetiapine 12.5 mg at bedtime was initiated, but severe orthostatic hypotension resulted when the dose was increased to 25 mg daily without improvement in psychosis. Episodes of violent agitation were becoming more frequent and difficult to control. At this time, a trial of clozapine to treat Mr. P’s severe psychosis was considered.
Dementia with Lewy bodies may be one of the most common causes of dementia, and yet remains a challenge to treat. In neuropathologic autopsy studies of patients with dementia, findings consistent with DLB were reported in 15-25% of all cases, making it the second largest pathologic subgroup of dementia next to pure Alzheimer’s disease.1-4 Lewy bodies are intracytoplasmic neuronal inclusion bodies that have been identified in subcortical nuclei in Parkinson’s disease. The abnormal accumulation of alpha-synuclein protein results in the formation of Lewy bodies.5 In DLB, these inclusion bodies are also found in the brain stem and throughout the cerebral cortex.1,5 The clinical criteria for this type of dementia, as defined by McKeith et al,1 includes progressive cognitive decline accompanied by two out of three of the following additional features: fluctuating cognition, recurrent visual hallucinations, and spontaneous motor features of Parkinson’s disease. Other features that support the diagnosis include repeated falls, syncope, transient loss of consciousness, neuroleptic sensitivity, systematized delusions, and other forms of hallucinations (Table).1,2,4,6
The psychiatric symptoms that can be seen in DLB are common. Visual hallucinations can occur in up to two-thirds of cases.3,6 Sensitivity to neuroleptic drugs in patients with DLB makes treating the psychosis that can occur in this illness a challenge. Oversedation, extreme rigidity, postural instability, immobility, confusion, and delirium have all been described in patients with DLB treated with neuroleptics.3,7-9 Sensitivity has occurred, even with the use of low-potency agents and with newer-generation neuroleptics at low dosing.8 Chacko et al,10 however, have described efficacy and tolerability with cloza-pine in a patient with DLB. The use of clozapine in this difficult-to-treat population may be worth further consideration. Clozapine was considered to treat ongoing psychotic symptoms in this patient who met clinical criteria for DLB, and was unable to tolerate other atypical antipsychotic agents, even in very low doses.
In Mr. P, significant worsening of symptoms occurred over time, coinciding with the escalating use of other neuroleptic drugs. He displayed prominent drug sensitivity with respect to extrapyramidal symptoms (EPS), autonomic instability, and alteration in mental status. Side effects such as EPS, orthostatic hypotension, and delirium are certainly more likely to occur in patients already at risk due to parkinsonian symptoms, autonomic instability, and dementia. Clozapine, an atypical antipsychotic with relatively weak D2 receptor antagonist activity, is effective in treating psychosis in patients with schizophrenia, and is believed to have the lowest incidence of extrapyramidal side effects of the drugs in this class. Several reports have demonstrated the efficacy of clozapine in treating patients with Parkinson’s disease with psychosis or L-dopa–induced psychosis.3,11,12 Its efficacy in this population is most likely related to the favorable side-effect profile that has minimal impact on motor function.
Due to the close pathological relationship between Parkinson’s disease and DLB, use of clozapine to treat psychosis in patients with DLB is a therapeutic option that may offer benefits with less motor side effect. There are significant risks associated with clozapine, including agranulocytosis requiring weekly blood count monitoring, as well as the potential for significant weight gain and developing diabetes mellitus. Recently, the monitoring requirement was enhanced by the Food and Drug Administration (FDA) to include both white blood cell and absolute neutrophil count in order to identify early neutropenia.13 Although these risks should always be carefully considered, the ability to treat psychosis in DLB may be necessary to preserve the safety of the patient and others around him or her, as well as provide an opportunity to improve the quality of life for the patient and his or her caretakers. Cholinesterase inhibitors also have been utilized in the treatment of patients with DLB, with some studies suggesting that rivastigmine is better tolerated and may offer some benefit in reducing behavioral symptoms.14 Other agents may also be useful, but limited published data are available. It should not be overlooked that DLB may account for a large proportion of dementia cases. Skills in diagnosis and treatment considerations for this disease require further review. Although this is only a single case demonstrating the efficacy of clozapine in a patient with DLB, it may provide future guidance for clinicians attempting to treat this challenging population.
OUTCOME OF THE CASE PATIENT
Mr. P was started on clozapine 6.25 mg at bedtime. The dose was slowly titrated to 75 mg at bedtime. Some excess morning sedation and mild orthostasis was noted at this dose. Clozapine was therefore decreased to 62.5 mg at bedtime. At this dose of clozapine, Mr. P began to show remarkable improvement. Episodes of paranoia, agitation, and physical aggression no longer occurred. He no longer required use of a vest restraint for safety, and did not report any visual hallucinations. He became more alert and oriented. Gradually, he became more cooperative with care and could engage in appropriate social interactions with others. Mr. P’s affect was now full and reactive. He began to ambulate independently. The patient remained off Parkinson’s disease medications after the titration of clozapine, and his extrapyramidal symptoms did not significantly worsen. Although the right upper-extremity tremor, shuffling gait, and decreased arm swing persisted, there was no significant cogwheel rigidity or impaired mobility. Treatment with clozapine was well tolerated to successfully control his psychosis and agitation. After a 54-day hospital course, Mr. P was considered stable for discharge from acute psychiatric care. He was transferred to a skilled nursing facility, where he continued to receive psychiatric follow-up care.
This work has been funded through the AAGP/Bristol-Myers Squibb Fellowship Program.
The author reports no relevant financial relationships.