Pharmaceutical Research

Studies examine the safety of prescribing antipsychotics, acetylcholinesterase inhibitors, and beta-blockers to older adults

Antipsychotic medications are prescribed for over a fourth of U.S. Medicare patients in nursing homes for dementia, delirium, psychosis, agitation, and affective disorders, and for unapproved indications. Acetylcholinesterase inhibitors (AChEIs) and beta-blockers are commonly prescribed for patients with Alzheimer's disease (AD), up to 15 percent of whom also suffer from chronic airway disorders such as asthma and chronic obstructive pulmonary disease (COPD).

Two studies supported by the Agency for Healthcare Research and Quality recently examined the safety of prescribing these medications for the elderly. The first study (AHRQ Contract No. 290-20-0050) concluded that conventional antipsychotics and the newer atypical antipsychotics are equally risky for use in the elderly. The second study (HS10881) found that use of AchEIs, typically contraindicated for elderly persons with chronic airway disorders, is safe for this group as physicians are currently prescribing them, but beta-blockers are not. Both studies are summarized here.

Schneeweiss, S., Setoguchi, S., Brookhart, A., and others (2007, February). "Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients." Canadian Medical Association Journal 176(5), pp. 627-632.

There has been a rapid shift away from first-generation conventional antipsychotics (for example, chlorpromazine, haloperidol, and loxapine) to more actively marketed second-generation atypical agents (for example, clozapine, olanzapine, quetiapine, and resperidone). Canadian and U.S. Food and Drug Administration health advisories warn that use of atypical antipsychotics increases the risk of dying among elderly patients with dementia. However, physicians should consider both conventional and atypical antipsychotics to be equally risky in elderly patients, according to this study. The researchers linked health care use data of all British Columbia residents to identify elderly persons who began taking antipsychotic medications between 1996 through 2004. They compared the 180-day death rates between those taking conventional and those taking atypical antipsychotics.

Of the 37,241 elderly people studied, 12,882 were prescribed a conventional antipsychotic and 24,359 were prescribed an atypical antipsychotic. Within the first 6 months of drug use, 14.1 percent of the conventional drug group died compared with 9.6 percent in the atypical drug group. This was a 32 percent greater, dose-dependent risk of death among conventional drug users, after adjusting for other factors affecting mortality. This is a greater risk of dying than all measured health conditions except congestive heart failure and HIV infection, note the researchers.

Compared with the atypical agent, resperidone, the conventional agent, haloperidol, was associated with the greatest increase in risk of death (more than twice the risk), and loxapine, another conventional agent, with the lowest mortality increase (29 percent). The greatest increase in mortality (60 to 67 percent) occurred among people taking above median doses of conventional antipsychotic medications and during the first 40 days after the start of drug therapy.

Thacker, E.L. and Schneeweiss, S. (2006, November). "Inhibition of acetylcholinesterase inhibitors and complications of chronic airways disorders in elderly patients." Drug Safety 29(11), pp. 1077-1085.

Chronic airway disorders are considered contraindications for the beta-blockers and AchEIs (for example, donepezil, rivastigmine, and galantamine) commonly prescribed for Alzheimer's disease. This sequence-symmetry study concluded that physicians can safely prescribe AchEIs to elderly patients with chronic airway disorders, but beta-blocker prescribing continues to result in adverse health outcomes.

The research team analyzed Medicare beneficiaries with a history of chronic airway disorders who had drug coverage between 1997 and 2002. One group of 922 patients began treatment with an AchEI, and the other group of 2,819 patients began treatment with a beta-blocker.

Elderly patients who began taking AchEIs had no significant increase in emergency room visits, hospitalizations, or physician visits for complications of chronic airway disorders compared with before the initiation. This group also had no dispensing of an antibacterial drug and an oral corticosteroid on the same day of such encounters, an indication of airway disorder complications, after adjusting for age, sex, race, and other factors. In contrast, patients who began using beta-blockers had a two- to three-fold increased rate of complications in the month after treatment began. These problems probably resulted from bronchoconstriction.

Physicians may be aware of the potential adverse effects of AchEIs and selectively prescribe them to patients who have less severe chronic airway disorders and who are at low risk of complications. On the other hand, AchEIs used for dementia treatment may not be associated with serious adverse respiratory effects, suggest the researchers. However, they caution that their results do not mean that AchEIs should be indiscriminately prescribed to elderly patients with chronic airway disorders or that warnings related to COPD and asthma patients in AchEI prescribing packets are unnecessary. Rather, the results indicate that in current clinical practice, doctors seem to be prescribing AchEIs but not beta-blockers appropriately for this group.

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