Joined: Fri Aug 11, 2006 1:46 pm
Location: SF Bay Area (Northern CA)
"Pathophysiology and treatment of psychosis" in PD
I picked up a few new things from this recently-published abstract. First, the use of antidepressants to treat psychosis is new to me: "Limited case reports also suggest that specific antidepressants (i.e. clomipramine and citalopram) may improve psychosis in depressed patients."
Second, this statement is interesting: "With regard to non-pharmacological interventions, case reports suggest that electroconvulsive therapy has the potential to reduce psychotic symptoms and may be considered in cases involving concurrent depression and/or medication-refractory psychosis."
I'm only aware of a handful of people who have an atypical parkinsonism disorder with severe depression who have tried ECT. I remember one caregiver reported great success with ECT. I think it's such a controversial treatment, however, that more have probably been treated with ECT and the caregivers are reluctant to report it.
Third is this list of intrinsic factors that can potentially explain psychosis: "visual processing deficits (e.g. lower visual acuity, colour and contrast recognition deficits, ocular pathology and functional brain abnormalities identified amongst hallucinating PD patients); sleep dysregulation (e.g. sleep fragmentation and altered dream phenomena); ...and genetics (e.g. apolipoprotein E epsilon4 allele and tau H1H1 genotype)."
Here's the abstract of this review article:
Drugs & Aging. 2008;25(8):665-82.
Pathophysiology and treatment of psychosis in Parkinson's disease: a review.
Zahodne LB, Fernandez HH.
Department of Clinical and Health Psychology and Movement Disorders Center, McKnight Brain Institute, University of Florida, Gainesville, Florida.
Psychotic symptoms in Parkinson's disease (PD) are relatively common and, in addition to creating a disturbance in patients' daily lives, have consistently been shown to be associated with poor outcome. Our understanding of the pathophysiology of psychosis in PD has expanded dramatically over the past 15 years, from an initial interpretation of symptoms as dopaminergic drug adverse effects to the current view of a complex interplay of extrinsic and disease-related factors.
PD psychosis has unique clinical features, namely that it arises within a context of a clear sensorium and retained insight, there is relative prominence of visual hallucinations and progression occurs over time. PD psychosis tends to emerge later in the disease course, and disease duration represents one risk factor for its development. The use of anti-PD medications (particularly dopamine receptor agonists) has been the most widely identified risk factor for PD psychosis. Other risk factors discussed in the literature include older age, disease severity, sleep disturbance, cognitive impairment, dementia and/or depression.
Recent efforts have aimed to explore the complex pathophysiology of PD psychosis, which is now known to involve an interaction between extrinsic, drug-related and intrinsic, disease-related components. The most important extrinsic factor is use of dopaminergic medication, which plays a prominent role in PD psychosis. Intrinsic factors include visual processing deficits (e.g. lower visual acuity, colour and contrast recognition deficits, ocular pathology and functional brain abnormalities identified amongst hallucinating PD patients); sleep dysregulation (e.g. sleep fragmentation and altered dream phenomena); neurochemical (dopamine, serotonin, acetylcholine, etc.) and structural abnormalities involving site-specific Lewy body deposition; and genetics (e.g. apolipoprotein E epsilon4 allele and tau H1H1 genotype). Preliminary reports have also shown a potential relationship between deep brain stimulation surgery and PD psychosis.
When reduction in anti-PD medications to the lowest tolerated dose does not improve psychosis, further intervention may be warranted. Several atypical antipsychotic agents (i.e. clozapine, olanzapine) have been shown to be efficacious in reducing psychotic symptoms in PD; however, use of clozapine requires cumbersome monitoring and olanzapine leads to motor worsening.
Studies of ziprasidone and aripiprazole are limited to open-label trials and case reports and are highly variable; however, it appears that while each may be effective in some patients, both are associated with adverse effects.
While quetiapine has not been determined efficacious in two randomized controlled trials, it is a common first-line treatment for PD psychosis because of its tolerability, ease of use and demonstrated utility in numerous open-label reports.
Cholinesterase inhibitors currently represent the most promising pharmacological alternative to antipsychotics. Tacrine is rarely tried because of hepatic toxicity, and controlled trials with donepezil have not shown significant reductions in psychotic symptoms, due perhaps to methodological limitations. However, results from an open-label study and a double-blind, placebo-controlled trial involving 188 hallucinating PD patients support the efficacy of rivastigmine.
With regard to non-pharmacological interventions, case reports suggest that electroconvulsive therapy has the potential to reduce psychotic symptoms and may be considered in cases involving concurrent depression and/or medication-refractory psychosis.
Limited case reports also suggest that specific antidepressants (i.e. clomipramine and citalopram) may improve psychosis in depressed patients.
Finally, studies in the schizophrenia literature indicate that psychological approaches are effective in psychosis management but, to date, this strategy has been supported only qualitatively in PD, and further studies are warranted.
PubMed ID#: 18665659 (see pubmed.gov for abstract only)
clozapine = Clozaril
olanzapine = Zyprexa
ziprasidone = Geodon
aripiprazole = Abilify
quetiapine = Seroquel
donepezil = Aricept
rivastigmine = Exelon
clomipramine = Anafranil
citalopram = Celexa
Joined: Thu Jul 03, 2008 11:05 am
Location: Raleigh, NC
Thanks for posting this, Robin. It brings to mind a question I've had about research. Who (specialty area) is doing most of the LBD research now? Is it mostly in the PD community? As happy as I am for all the advances reported in Alzheimer's research this week, it again has made me want to shout the reminder that all dementia is not Alzheimer's.