Neurology -- Correspondence for Friedman, 67 (4) 564-566

Correspondence published:

Atypical antipsychotics in the elderly with Parkinson disease and the "black box" warning: Carl E. Rosenkilde, MD, PhD (25 October 2006)

Reply from the Author: Joseph H Friedman, Warwick, RI 02886 (25 October 2006)

Atypical antipsychotics in the elderly with Parkinson disease and the "black box" warning 25 October 2006

Carl E. Rosenkilde, MD, PhD,
Northern Westchester Hospital
91 Smith Avenue, Mount Kisco, NY 10549
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Re: Atypical antipsychotics in the elderly with Parkinson disease and the "black box" warning

maribo{at}aol.com Carl E. Rosenkilde, MD, PhD

The black box warning concerns increased mortality after use of atypical antipsychotic (AA) drugs in elderly demented patients with psychosis. [1] Such warning will likely result in changing use of the medications. Dr Friedman emphasizes that it might be a disservice to our patients to withhold AAs.
The explanation of the increased mortality remains unclear and the clinician is left with no guidelines for the future use of the AAs as well as the older antipsychotic drugs. Inherent pharmacological properties of the drugs may not be the sole explanation. It is possible that the drugs sometimes are used inappropriately due to misdiagnosis of worsened delirious encephalopathy. Thus, the clinician may have failed to recognize presence of hypoxia, cardiac ischemia or infections.
In the absence of more obvious signs of acute illness in demented patients, the AA drug is prescribed for exacerbated agitation or hallucinations. Some patients may be particularly susceptible for misdiagnosis and ultimately death including: the very old, the severely demented, those admitted for acute or chronic care, and those with multiple co-existing medical problems.
Until further studies are available and more authoritative guidelines provided, these medications probably can be used without the warning of death as a side effect but with an understanding among the caretakers of the need for reevaluation of the confused patient.
Underlying acute medical problems should be explored in the demented patient with altered mental status. Use of AAs should be reserved for those instances when acute medical illness appears unlikely after careful clinical re-assessment.
Reference
1. Friedman JH. Atypical antipsychotics in the elderly with Parkinson disease and the "black box" warning Neurology 2006; 67: 564-566.
Disclosure: The author has served as a certified PANSS trainer for the PANSS Institute, LLC.

Reply from the Author 25 October 2006

Joseph H Friedman,
NeuroHealth
227 Centerville Rd , Warwick, RI 02886,
Warwick, RI 02886
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Re: Reply from the Author

Joseph_Friedman{at}brown.edu Joseph H Friedman, et al.

I share Dr. Rosenkilde�s concerns about the potential underuse of atypical antipsychotics in the elderly demented. I do not think we can explain away the increased mortality by invoking misdiagnosis or increased medical problems in this population because the �black box� warning was based on placebo controlled trials.
Unless we find fault with the individual trials we must assess the causes of increased death rates. It is possible that the diagnoses used for entering the studies were incorrect but I don�t think we can ignore a study because of unfounded suspicions, especially when the results are supported by several studies involving different drugs.
On the other hand, I do believe that Dr. Rosenkilde is generally correct in his analysis. My own hypothesis, which is probably the most common one, is that the side effects of sedation, orthostatic hypotension, and worsened (often unrecognized) parkinsonism are the culprits. The questions are not so much whether these drugs increase mortality, but whether alternatives such as benzodiazepines, first-generation antipsychotics, or cholinesterase inhibitors are any safer, and how they compare on measures of efficacy and quality of life.
Disclosure: J.H.F. has received funds for consultation, research or speaking honoraria from the following potentially involved companies: Astra Zeneca, Janssen, Novartis, Acadia Pharmaceuticals, Ovation Pharmaceuticals. J.H.F. has also received funds from noninvolved companies: Teva, Glaxo Smith Kline, Boehringer Ingleheim Pharmacia, Cephalon, Solvay.