Treating psychosis in PD and use of antipsychotics

This post will interest those dealing with hallucinations or delusions, or those using atypical antipsychotics, such as Seroquel. This contains a nice summary of why antipsychotics are used and which ones are preferred.

This was posted yesterday on the National Parkinson Foundation’s “Ask the Doctor” online forum. I believe it’s an excerpt from a larger publication on treatment of PD. I learned three things. First, “double-blinded trials of quetiapine have been disappointing.” (quetiapine = Seroquel) Second, “odansetron (a rather expensive anti-nausea medication used mainly for patients undergoing chemotherapy)” is a treatment option for psychosis in PD. I’m pretty sure that’s a typo and what is meant is ondansetron or Zofran. Third, the effects of electroconvulsive therapy (ECT) in treating psychosis are short-lived.


Posted by Dr. Hubert H. Fernandez
Posted on 1/30/10

What medications can be used to treat psychosis in Parkinson’s disease?

Just like the management of cognitive decline, prior to starting any treatment, one has to search for urinary tract infections, pneumonia, metabolic derangements, sleep disturbances, brain insults (such as strokes) and social stressors, such as changes in the environment, as possible explanations for hallucinations or delusions. Medications that can alter brain mechanics because of their ability to penetrate the brain’s “iron curtain” (termed the “blood brain barrier”) that is designed to keep away unwanted substances, such as narcotics, hypnotics, antidepressants, and anxiolytics are also common culprits. If psychotic symptoms persist despite the withdrawal of other psychotropic medications, anti-Parkinson’s disease medications may be gradually reduced or, if necessary, discontinued. As mentioned in Module 4, most authorities recommend “peeling off” these medications in the following order: anticholinergic agents, amantadine, monoamine oxidase inhibitors, dopamine agonists, catechol-O-methyltransferase inhibitors, and finally, levodopa. Regular or short acting formulations of levodopa are preferred in patients prone to hallucinations over sustained-release formulations because their pharmacokinetics are more predictable and there is less potential for cumulative side-effects. If psychosis improves, the patient is then maintained on the lowest possible dose of anti- Parkinson’s disease medications. However, if the withdrawal of anti-PD drugs significantly worsens other Parkinson’s disease symptoms or does not control psychosis one must consider the addition of antipsychotic agents.

The choice of an antipsychotic agent is based largely on its ease of use and side effect profile as most antipsychotics have comparable efficacy in improving psychosis. “Atypical” antipsychotics (or newer generation antipsychotics) are generally preferred given the significant risk of motor complications and anticholinergic side effects with older, conventional antipsychotics. The use of an appropriate atypical antipsychotic agent may allow the clinician to control psychosis with fewer motor side effects and, in some cases, without the need for significantly cutting back on anti- Parkinson’s disease medications. Clinicians should be aware that the FDA issued a “black box” warning for the use of these agents in the treatment of psychosis associated with dementia due to increased cardiac mortality. However, the majority of clinicians treating these patients continue to use these medications because these medications are efficacious, the absolute risk of increased mortality is low and the risk appears to be present in the older antipsychotics as well.

The main difference in the antipsychotics lies in their propensity to worsen motor functioning in this frail and already vulnerable population. Quetiapine has been studied in Parkinson’s disease patients and appears to have less potential for worsening motor function than risperidone, aripiprazole, olanzapine and ziprasidone. While double-blinded trials of quetiapine have been disappointing, it remains the first-line agent used for drug-induced psychosis in Parkinson’s due to its tolerability and good track record in several open-label trials .

The use of clozapine is generally limited to patients who have failed other agents, despite its superior efficacy over all other antipsychotic drugs, because of its very uncommon risk of agranulocytosis (meaning, sudden drop in white blood cell count—our body’s first defense against ordinary infections). The chances of this complication developing are less than 1%. Nonetheless, in the United States, for the first six months, each patient on clozapine must undergo a weekly white blood cell count and can receive only one week’s supply of the drug at a time. After 6 months the process becomes bi-weekly.

It remains unclear how long antipsychotic medications should be continued once they are initiated. There are some data that show persistence of hallucinations in Parkinson’s disease patients with drug-induced psychosis after its initial occurrence. At the University of Florida, we prospectively followed our own patients with Parkinson’s disease on successful long-term treatment with quetiapine or clozapine to see if they could be successfully weaned off their antipsychotic drugs. The study was aborted after enrollment of only six patients due to an unacceptably high rate of psychosis recurrence (five patients, 83%).

Other treatment options include acetylcholinesterase inhibitors, odansetron (a rather expensive anti-nausea medication used mainly for patients undergoing chemotherapy) and electroconvulsive therapy (ECT). Several open-label studies have found that cholinesterase inhibitors may improve hallucinations and psychosis in Parkinson’s disease subjects. Similarly, an open-label trial with 16 Parkinson’s disease patients showed marked improvements in the areas of visual hallucinations, confusion, and functional impairment with no adverse effects on motor function. This result has yet to be reproduced by other investgators. ECT should be reserved for patients who are unresponsive to, or intolerant of, other treatments, especially if the psychosis is associated with severe depression. In general, ECT’s effects are short-lived, and repeated treatments and/or the help of other medications are required to maintain benefits.

[Robin’s note: I think the open-label trial with 16 PD patients above is a trial with ondansetron. And I think there’s a typo above in the drug’s name: an N is missing. The brand name is Zofran.] [Brand names for some of the antipsychotic medications referred to include:
quetiapine = Seroquel
risperidone = Risperdal
aripiprazole = Abilify
olanzapine = Zyprexa
ziprasidone = Geodon
clozapine = Clozaril ]