Use of antipsychotics in patients with dementia and risk of death

Antipsychotic medications are widely used in dementia to control behavioral symptoms. Many studies noted a relationship between increased risk of death among dementia patients and the use of antipsychotics. However, most patients experience difficult to manage behavioral symptoms in dementia and the death may be due to the disease process itself.  

Study published in American journal of psychiatry looked into the mortality among dementia patients who are treated with various anti-psychotic medications. This study compared differences between deaths rates in different anti psychotics using historical data.

According to this study Haloperidol (Haldol) is associated with most number of deaths. Quetiapine (Seroquel) is associated with lowest death rates. Other antipsychotics such as Risperdal, and Zyprexa, lay in-between.

Analysis of this study

However, there is a caveat in this study. It is that this study used archived data. In these data most people with severe dementia were given haloperidol, because some clinicians believed that Haldol is more effective in controlling behavioral symptoms than other antipsychotics. Therefore, naturally they used Haldol frequently in patients with more severe dementia. These patients have high death rates even without any antipsychotics. Therefore, this study may be biased toward newer anti psychotics.

In addition, we need to understand that there are very strong pharmaceutical companies to promote newer antipsychotics. Nobody promotes older antipsychotics such as Haldol even though they are preferable in certain patients.

Journal article in American journal of Psychiatry

Risk of Mortality Among Individual Antipsychotics in Patients With Dementia

Effects of antipsychotic medications on dementia – Analysis of CATIE-AD study

Dementia is known to cause memory impairment, personality change, problems in judgments, and intellectual impairment. These changes taken together are called impairments in cognitive capacity.

Doctors usually prescribe antipsychotic medications for dementia, especially to calm down acutely disturbed patients. In addition, some patients are given regular dose of antipsychotics as a maintenance therapy to improve sleep and agitation. Most common antipsychotics prescribed are Risperidone (Risperdal®), Quetiapine (Seroquel ®), and Olanzapine (Zyprexa®).

However, there is a recent debate among doctors regarding the long term outcome of this practice. One of the reasons is the blood lipid abnormalities seen in patients who are prescribed atypical antipsychotics such as Risperidone (Risperdal®), Quetiapine (Seroquel ®), and Olanzapine (Zyprexa®). This could lead to heart problems such as heart attacks. In addition, these problems could increase the memory impairment seen in Alzheimer's disease due to blockage of vessels in the brain.

Now doctors have concluded several studies on this regard. One of such is the “Clinical Antipsychotic Trials of Intervention Effectiveness–Alzheimer's Disease study (CATIE-AD)” study. As the name suggest it looked into the relationship between prescription of antipsychotic medications and Alzheimer’s dementia. This study mainly looked at memory impairment and other cognitive impairments seen in dementia patients who are prescribed antipsychotics.

How the CATIE-AD study is conducted?


This study carried out in more than 400 patients. Most of them are community dwelling moderate to severe dementia patients. These patients were randomly allocated to different treatment groups and they were prescribed Risperidone, Quetiapine and Olanzapine. In addition, patients were given different medications in different times similar to crossover design. This study was carried out around three years.

Results of the study


This study reported a statistically significant cognitive impairment associated with antipsychotic medications. That means people who were prescribed antipsychotics showed greater memory impairment than the people who were not prescribed them.

Background


Many other studies that were performed around the time showed conflicting results.

Conclusions
This study is not a very large study and the cross over design can have many problems that would change the outcome. However, it will certainly put more weight on the argument that antipsychotics cause cognitive impairment. But other options available for agitation and psychosis seen in dementia patients such as benzodiazepines may also cause cognitive impairment. Therefore, in practice it is difficult to stop prescribing antipsychotics for patients with dementia.

Sources
Consequences of Antipsychotic Medications for the Dementia Patient - Am J Psychiatry 168:767-769, August 2011

Side effects of Namenda or Memantin (generic name)

This is a medication prescribed for dementia caused by Alzheimer’s disease. In addition, Namenda is also prescribed for other memory disorders and chronic pain syndromes. It can help Alzheimer’s disease patients to think more clearly and do activities of daily living. However, it cannot cure Alzheimer’s disease. Side effects of this drug are usually tolerable.


This drug has quite unusual mechanism of action. It causes mild reduction in glutamate neurotransmission inside the brain. It causes reduction in exitotoxicity that is associated with glutamate neuro transmission. This results in prolongation of neuronal survival. But this drug is rather expensive and most patients in developing world could not afford it. In addition, long term cost benefit ratio is rather controversial. 

Most common side effects of Namenda

Most common side effects of Namenda are constipation, Dizziness and headache. In addition, Namenda can rarely cause seizures. Weight gain is minimal. But it is reported in some patients. Some patients may get excessive fatigue. Namenda  usually do not cause any sexual side effects. 

Does Namenda cause sedation?

This is a question frequently asked from me. Namenda can cause drowsiness and sedation but it is little rare. Since it can cause fatigue, some patients may find it comfortable to lie on the bed, which can cause sleepiness.