Psychiatric Aspects of Parkinson's Disease

Uwe Ehrt; Dag Aarsland

Disclosures

Curr Opin Psychiatry. 2005;18(3):335-341. 

In This Article

Psychosis and Other Neuropsychiatric Symptoms in Parkinson's Disease

Psychosis, most commonly visual hallucinations, occurs in about one third of patients with Parkinson's disease and causes reduced quality of life, early institutionalization and increased mortality.[55] It is more common in PDD than non-demented Parkinson's disease patients. Non-specific factors, such as intercurrent infection and delirium, as well as disease-related factors and dopaminergic treatment may contribute to visual hallucinations.

Marsh et al .[56] described psychiatric comorbidity on a syndromic level among 116 Parkinson's disease patients using the semi-structured Structured Clinical Interview for DSM-IV. Twenty-five (22%) patients experienced psychosis.[56] Among them, 11 had psychosis alone, the remaining 14 patients had at least one other comorbid disorder, depression (71%), anxiety disorder (21%), apathetic syndrome (14%) and delirium (14%). With these high comorbidity rates, and the potential negative impact of psychosis on the affective state, it was concluded that the diagnosis of psychosis should prompt an assessment of depression and vice versa. A study of the personality of Parkinson's disease patients confirmed earlier findings of reduced novelty seeking and increased harm avoidance, and related this to a deficit in the mesolimbic dopamine transmission of the left hemisphere and to a greater dopamine loss in the striatum.[57]

Treatment

The results from a new study support previous studies suggesting that psychosis in Parkinson's disease is rather 'endogenic' and not only related to dopaminergic treatment. In a consecutive sample of 422 Parkinson's disease patients the group experiencing hallucinations ( n = 90) received comparable doses of levodopa to the patients without hallucinations.[58*] Furthermore, supplementary treatment with other dopaminergic or anticholinergic drugs was not associated with visual hallucinations. This is of clinical importance, and the authors propose that antipsychotic drugs rather than reduction of the antiparkinsonian drugs should be the therapy of first choice against hallucinations.

Parkinson's disease patients do not generally tolerate classical antipsychotic drugs, and there is much interest in data on newer atypical substances. As is the case in DLB,[59] Parkinson's disease patients, and in particular those with dementia, may experience marked sensitivity reactions even to atypical antipsychotics. Studies of risperidone[60] and olanzapine[61—63] have reported an unacceptable risk of motor deterioration.

In a single-blind randomized trial on 45 Parkinson's disease patients with drug-induced psychosis quetiapine, at a mean dose of 91 ± 47 mg, after 12 weeks was as effective and well-tolerated as clozapine, at a dose of 26 ± 12 mg, as assessed by change on the Brief Psychiatric Rating Scale,[64*] thereby supporting previous open-label studies. Unfortunately, placebo-controlled studies of quetiapine in Parkinson's disease have not yet been reported. Although most studies suggest that quetiapine is safe even in Parkinson's disease, some reports suggest that there is a risk of adverse motor effects in these frail patients, predominantly in demented subjects.[65]

Preliminary data on the novel partial D2 agonist aripiprazole in Parkinson's disease are not encouraging.[66] Only two of the eight treated Parkinson's disease patients experienced complete resolution, the others had to discontinue within 40 days, two of whom because of worsening of motor symptoms. In another case report, aripiprazole caused severe exacerbation of motor function without improving psychosis.[67]

Forty-six patients completed a double blind placebo controlled study, which confirmed the efficacy of low dose clozapine in Parkinson's disease related psychosis.[68*] A dosage not higher than 50 mg was used. No motor impairment was registered. One novel aspect of this study was the systematic withdrawal of clozapine after complete remission. A relapse was observed in three-quarters of the patients. Once started, the antipsychotic treatment should be continued to prevent 'rebound psychosis'. Fernandez et al .[69*] tried to discontinue quetiapine or clozapine in stable apsychotic Parkinson's disease patients with previous psychosis. This study was stopped since psychosis recurred in five of the first six patients, in three cases worse than the original psychotic episode.

Since atypical antipsychotic agents other than clozapine have not yet proven effective for psychosis and may worsen motor symptoms in Parkinson's disease, other drug treatments are needed. There is preliminary evidence that cholinesterase inhibitors, which do not seem to worsen motor symptoms in Parkinson's disease, have some beneficial effect on visual hallucinations in Parkinson's disease.[23**,33] No placebo-controlled study, however, has yet explored the effect of cholinesterase inhibitors in Parkinson's disease patients with psychosis. Serotonin may also be involved in hallucinations in Parkinson's disease, and Voon and Lang[70] reported improvement of depression as well as psychosis in a patient with Parkinson's disease.

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