Drug Benefit Trends.
No. 2
Parkinson Disease
Psychiatric Symptoms Associated With Parkinson Disease
By Matthew A. Menza, MD |
March 26, 2010
Dr Menza is professor of psychiatry and neurology and interim chair in the department of psychiatry at the Robert Wood Johnson Medical School in Piscataway, NJ.
Delusions, uncommon in the first 2 years of therapy, may also occur and, as with hallucinations, are often preceded by vivid dreams. Delusions are usually persecutory: fears of being injured, influenced, poisoned, filmed, or tape-recorded are common.16 In severe cases, the psychotic symptoms are virtually indistinguishable from those seen in schizophrenia.
There are convincing data that suggest that dopamine(Drug information on dopamine)rgic treatments may be associated with the development of a variety of impulse control disorders in some patients.17 The impulse control disorders, which may include severe gambling and hypersexuality as well as shopping and binge eating, can be extremely disruptive to patients and families. As with psychosis, impulse control disorders are more commonly associated with the dopamine agonists pramipexole(Drug information on pramipexole) and ropinirole(Drug information on ropinirole).18
This is particularly fascinating because these disorders occur in a population that apparently has a reduced risk for these behaviors before the onset of PD and the use of dopaminergically active drugs. This association between treatments that increase dopamine and impulse control problems is consistent with our understanding of the role of the dopamine system in pleasure and reward, as well as with the known impairment in executive function in PD. Given the impact of these disorders, patients should be educated and monitored for the early signs of these disturbances.
Treatment of all these drug-induced symptoms generally involves a decrease in the dosage of the antiparkinsonian medication. Direct dopamine agonists are the first target, followed by the anticholinergics and by levodopa(Drug information on levodopa) preparations.19 Unfortunately, decreasing the dosage of the antiparkinsonian drugs often results in an increase in the movement disorder. This has been referred to as the “motion-emotion conundrum.”20
Atypical antipsychotics may be of help in this setting. A variety of studies have examined the tolerability and efficacy of these drugs in patients with PD; they show that drugs with high affinities for the D2 receptor (typical antipsychotics, risperidone, and aripiprazole(Drug information on aripiprazole)) are not tolerated. Low-dose quetiapine(Drug information on quetiapine) is widely used, although results of controlled trials have been equivocal.21
Open-label and controlled trials have shown clozapine(Drug information on clozapine) to be useful in PD patients with psychoses.22 The use of clozapine is more problematic because of the risk of agranulocytosis as well as the anticholinergic, sedative, and orthostatic hypotensive adverse effects. Nonetheless, clozapine causes very few extrapyramidal symptoms, and when it is used in low doses, it can block psychotic symptoms without worsening rigidity. Doses starting at 6.25 to 12.5 mg and titrating to 50 mg are typical. Plasma levels from 4.5 to 16.1 ng/mL are associated with good response.
Dementia
PD is associated with subtle but widespread cognitive impairment, even in the absence of clinically apparent cognitive decline or frank dementia. Early in the course of the illness or at the time of diagnosis, there are difficulties with memory retrieval, executive functioning, attention, and visuospatial abilities—all of which are associated with significant functional impairment.23 As noted, more severe cognitive impairment, including dementia, also occurs commonly in patients with PD. The average prevalence of dementia, which generally occurs later in the illness, is 39.9%.24 A long-term study of PD patients in a community setting found that dementia had developed in about 26% of them 9 years after the onset of PD; after 13 years, this number increased to about 52%, and after 17 years reached 78%.25
While the anticholinesterase drugs are available for treatment of dementia, their use in PD is somewhat limited by their efficacy and tolerability.26 In the largest randomized trial, clinically meaningful improvement occurred in 5.3% more patients who received rivastigmine(Drug information on rivastigmine) compared with those who received placebo.27 The most common adverse effects were nausea, vomiting, and tremors. In addition, a small study with memantine(Drug information on memantine) found that it produced a small effect over placebo and was well tolerated.28
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