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 Antipsychotics 
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Joined: Mon Jun 05, 2006 3:29 pm
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Location: State College, PA
Post Antipsychotics
For those who have questions about antipsychotics...

I am not a physician, so I cannot dispense any medical advice. I am however deeply involved with the Lewy Body Dementia Association, and would like to share my layman's understanding of the issues facing caregivers about the use of antipsychotics.

The first line of treatment in LBD is normally the use of a cholinesterase inhibitor, which is approved by the FDA for Alzheimer's - Aricept, Exelon or Reminyl. They have been shown to help help cognition and reduce psychiatric features of LBD in some people, so that's always the safest first step.

Regarding antipsychotic medications... The biggest risk is associated with traditional antipsychotics, like Haldol. Those are absolutely contraindicated in LBD. The atypical antipsychotics, like Seroquel, are definitely less problematic, though not entirely without risk. That is why the doctors should follow the theory of 'Start low, go slow' any time they prescribe atypical antipsychotics.

The issue of antipsychotics is very sticky in LBD. It's balancing the need to improve the quality of life for both patients and caregivers with the risks of any side effects from them. This is a decision that must be made jointly by the treating physician and the caregiver/family so that everyone can feel comfortable that they have made the best decision in their individual circumstances.

Sometimes the choice seems clear, like if the hallucinations are causing the patient to behave in a life-threatening manner to themself or a caregiver. In that situation, the risk of side effects seems very tolerable.

Othertimes it may be less clear when trying to select the lesser of two evils. For example, the patient is agitated or anxious because of the hallucinations, and the caregiver is getting little sleep. Nobody is doing well, and the stress/worry magnifies the burden on the caregiver.

Sometimes, hallucinations are frequent but more benign, and there doesn't seem to be a reason to risk potential side effects.

Keeping a detailed journal about the patient's response to any medication changes will help both you and your doctor make future decisions about what medications to use.

Hoping that's helpful to someone,
Angela[/b]


Thu Jul 06, 2006 8:37 am
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post "Antipsychotic Drug Use and Mortality" (June 07 An
The use of atypical antipsychotics is such a hard choice for LBD families to make. Here's more fuel to the fire....

I got this full article -- "Antipsychotic drug use and mortality in older adults with dementia," Annals of Internal Medicine, 2007 Jun 5, PubMed ID#: 17548409 -- and read it recently. What makes this study so compelling is that because there's a national health service in Canada, the Canadian researchers have access to medication information (drugs prescribed, prescription date, whether it was refilled) and death dates.

Here are some excerpts from this very disturbing article:

A randomized, controlled trial (RCT) "involving 421 outpatients with Alzheimer disease and psychosis, aggression, or agitation concluded that the adverse effects of these newer drugs offset their advantages. As a result, improvements in behavioral symptoms with antipsychotic drug treatment do not necessarily lead to improvements in overall quality of life for patients or their caregivers."

"In April 2005, the US Food and Drug Administration issued a public health advisory that the use of atypical antipsychotics to treat elderly patients with dementia was associated with an increased risk for death compared with placebo. In June 2005, Health Canada issued a similar warning and additional data. These warnings stem from reviews of RCTs that involve the atypical agents risperidone, olanzapine, quetiapine, and aripiprazole. The mortality rate was approximately 1.6 to 1.7 times higher than with placebo and was greater with antipsychotics than with placebo in 15 of the 17 trials reviewed by the US FDA. The warnings extend to all currently available atypical antipsychotics."

Robin's note: The April 2005 FDA warning addresses these medications: olanzapine (Zyprexa), aripiprazole (Abilify), risperidone (Risperdal), quetiapine (Seroquel), clozapine (Clozaril), ziprasidone (Geodon), and Symbyax. You can find it online at:
http://www.fda.gov/cder/drug/advisory/a ... hotics.htm

Robin's note: The June 2005 Health Canada warning addresses these medications: risperidone (Risperdal), quetiapine (Seroquel), olanzapine (Zyprexa), and clozapine (Clozaril) You can find it online at:
http://www.hc-sc.gc.ca/ahc-asc/media/ad ... _63_e.html

"Studies have demonstrated that rates of antipsychotic prescribing are substantial among older adults newly admitted to long-term care facilities."

The breakdown of antipsychotic use was similar between the cohort that lived at home and the cohort that lived in a long-term care setting: atypical antipsychotics "users started treatment with risperidone (75.2%), olanzapine (19.6%), and quetiapine (5.2%)" and conventional antipsychotic "users started treatment with haloperidol (60.2%), loxapine (17.9%), thioridazine (1.3%)..."

"Our study provides further evidence that use of atypical antipsychotics is associated with a small but significant increase in mortality among older adults with dementia. In addition, the risk for death associated with antipsychotics is apparent after as little as 1 month of use and may persist for 6 months. Finally, these data provide independent confirmation of reports that use of conventional antipsychotics confers an even greater risk for death than does use of atypical antipsychotics."

"Our...study includes 5 times as many atypical antipsychotic users and nonusers as that in a meta-analysis of RCTs, includes many conventional antipsychotic users, and provides follow-up data to 6 months."

"Similar to our results, Wang and colleagues found that...(in) the first 180 days of use, the absolute event rates were dramatic: 17.9% of patients who began using conventional antipsychotics and 14.6% of patients who began using atypical antipsychotics died."

"The potential causes of death associated with antipsychotic use merit consideration. ... First, antipsychotics may prolong the QT interval, predisposing patients to arrhythmias and sudden cardiac death. Second, sedation and accelerated cognitive decline brought on by exposure to antipsychotics may increase the risk for aspiration syndromes and choking. ... Third, several studies have found a link between atypical antipsychotic use and venous thromboembolism... Fourth, a risk of cerebrovascular events may be associated with antipsychotic use, although this risk has been questioned. Finally, antipsychotics may contribute to events that are not initially recognized as the first step in a sequence that promotes premature death, such as falls leading to hip fractures."

Robin's note: causes of death were not examined in this study.

"In the US FDA and Health Canada reviews, the risk for death seemed to be a class effect with all atypical antipsychotics studied..."

Other researchers "suggest an approach that limits the use of these drugs to situation in which 'there is an identifiable risk of harm to the patient or others, when the distress caused by symptoms is significant, or when alternate therapies have failed and symptom relief would be beneficial'."

"Studies have shown that some patients receiving antipsychotics can be successfully weaned from these medications when monitored closely."

"Repetitive vocalizations or wandering" are symptoms that are "unlikely to respond to antipsychotic treatment."

"Clinical trials involving behavior management and caregiver education...may help to minimize antipsychotic use."


Sat Jul 28, 2007 2:21 am
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Post Re: "Antipsychotic Drug Use and Mortality" (June 0
robin wrote:
The breakdown of antipsychotic use was similar between the cohort that lived at home and the cohort that lived in a long-term care setting: atypical antipsychotics "users started treatment with risperidone (75.2%), olanzapine (19.6%), and quetiapine (5.2%)" and conventional antipsychotic "users started treatment with haloperidol (60.2%), loxapine (17.9%), thioridazine (1.3%)..."
."


Dear Robin,
Wow looking at these number's is certainly an eye opener, I know for us Risperidone was not a drug of choice, my husband took it for a very short time and he just was a crazy man. What concerns me now being on the other side of LBD, I have heard so many say that when they are in situations that might warrant a drug of this type many will say the end result is still better than their LO so agitated and honestly I often have agreed with that but I am not so sure anymore looking at these numbers.
If you don't mind I would like to save this to pass along when this comes up again?


Sat Jul 28, 2007 10:31 am

Joined: Fri Aug 11, 2006 1:46 pm
Posts: 4811
Location: SF Bay Area (Northern CA)
Post D2 receptor loss leads to neuroleptic sensitivity?
The newly-published abstract offers an explanation for why (many) LBDers experience adverse reactions (including greater cognitive decline) to antipsychotics (neuroleptics).

One of the authors - McKeith - is on the Scientific Advisory Council of the LBDA. (http://www.lewybodydementia.org/lbdasac.php)

You can either jump straight to the abstract or read the following list of excerpts from the abstract (I found it easier to read/understand this way):

"The use of neuroleptic medication to treat psychosis in both (DLB and AD) is of modest efficacy and can induce severe adverse reactions in DLB."

"Dopamine D2 receptors in the cerebral cortex are the...target for the antipsychotic...drugs..."

"D2 receptors were substantially...reduced in temporal cortex in DLB, and in DLB with concomitant Alzheimer pathology, but was not significantly changed in AD."

"This reduction correlated with greater cognitive decline..."

"(The) specific loss of D2 receptors associated with Lewy body pathology, in conjunction with our previous finding of low D2 receptors in striatum in DLB, provides a possible explanation for neuroleptic intolerance."

"That the reduction of D2 receptors correlated with cognitive decline suggests that neuroleptics, as dopamine D2 receptor antagonists, may have a deleterious effect on cognition in DLB."

Robin


Synapse. 2007 Jul 30;61(11):903-911 [Epub ahead of print]

Selective loss of dopamine D2 receptors in temporal cortex in dementia with Lewy bodies, association with cognitive decline.

Piggott MA, Ballard CG, Rowan E, Holmes C, McKeith IG, Jaros E, Perry RH, Perry EK.
Institute for Ageing and Health, Wolfson Research Centre, Newcastle General Hospital, Newcastle-upon-Tyne, UK.

Dementia with Lewy bodies (DLB) is a progressive dementia frequently accompanied by psychotic symptoms. Similar symptoms can occur in Alzheimer's disease (AD) to a lesser extent. The use of neuroleptic medication to treat psychosis in both diseases is of modest efficacy and can induce severe adverse reactions in DLB. Dopamine D2 receptors in the cerebral cortex are the putative target for the antipsychotic action of these drugs, but the status of these receptors in DLB is unknown. Autoradiography was used to examine the density D2 receptors in postmortem temporal cortex tissue from prospectively assessed patients with neuropathologically confirmed DLB and AD. D2 receptors were substantially (over 40%) and significantly (P < 0.001) reduced in temporal cortex in DLB, and in DLB with concomitant Alzheimer pathology, but was not significantly changed in AD. This reduction correlated with greater cognitive decline (P < 0.01), but was not significantly related to visual or auditory hallucinations or delusions. D2 receptor density was inversely correlated with cortical Lewy body pathology in the neocortex (P < 0.001). The specific loss of D2 receptors associated with Lewy body pathology, in conjunction with our previous finding of low D2 receptors in striatum in DLB, provides a possible explanation for neuroleptic intolerance. That the reduction of D2 receptors correlated with cognitive decline suggests that neuroleptics, as dopamine D2 receptor antagonists, may have a deleterious effect on cognition in DLB.

PubMed ID#: 17663455 (see pubmed.gov)


Wed Aug 01, 2007 7:13 pm
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