Atypical Attitudes: How The Atypicals Took the Fall in Dementia Patients–The Other Meds Catch Up

In 2008, the FDA put out the following:

“For Immediate Release: FDA Requests Boxed Warnings on Older Class of Antipsychotic Drugs.”

It said:

The U.S. Food and Drug Administration today exercised its new authority . . .to require manufacturers of “conventional” antipsychotic drugs to make safety-related changes to prescribing information, or labeling, to warn about an increased risk of death associated with the off-label use of these drugs to treat behavioral problems in older people with dementia.

In 2005, the FDA announced similar labeling changes for “atypical” antipsychotic drugs. At that time, Boxed Warnings, the FDA’s strongest, were added. The Boxed Warning will now be added to an older class of drugs known as “conventional” antipsychotics. [emphasis mine]


If you recall from yesterday’s post, the second-generation or ‘atypical’ antipsychotics were on the decline in treating the agitation and delusions of Alzheimer’s disease after the FDA’s 2005 warning, which included the dreaded Boxed Warning for each insert, indicating how serious the adverse effects of the meds could be in elderly patients.

The warning hit home, and prescribing patterns changed radically as the atypicals took a serious hit.

In a 2010 paper on the intended use of atypicals in dementia, the authors concluded,

review of physician audit data of intended usage shows a peak in atypical antipsychotic usage in April of 2005. Over the next five years, through July 2010, yearly totals of intended usage of atypical antipsychotics fell from over 700,000 to approximately 350,000; this is a decline of 50 percent. This analysis clearly shows a trend away from intended atypical antipsychotic usage since the advisory warning issued by the FDA.

So now, after three full years–and hundreds of thousands of prescription possibilities lost–the FDA returned to the topic of the atypical antipsychotics–only to to say that the first, older antipsychotics, which had been deemed safer for the elderly, were, in fact, also worthy of a serious danger warning–as much so as the atypicals.

In a sense, the atypicals had just taken the first blow–‘taking it for the team,’ so to speak–but, being first, the warning was also most memorable, and stuck in the public’s mind in a way that the second warning failed to do.


What to do? There is better response to the agitation and delusions of dementia from the antipsychotics than from other psychiatric meds–but there’s the black mark on their name.

So a sense of safety in prescribing remained now with antidepressants and benzodiazepines, a class of medications including Ativan, Xanax and Valium, that can be used to treat anxiety, as sedatives, as muscle relaxants, and even as anticonvulsants.

But then came a 2011 study, in the Canadian Medical Association Journal, “Risk of death and hospital admission for major medical events after initiation of psychotropic medications in older adults admitted to nursing homes.”*

The researchers analyzed a cohort of 10,900 patients admitted to a nursing home in British Columbia between 1996 and 2006, who were prescribed their first psychiatric medications in the nursing home. The following treatments were initiated for the following numbers of patients [residents who came in already taking meds were excluded, as were those on multiple classes of medications]:

1. Atypical antipsychotics: 1942
2. Conventional antipsychotics: 1902
3. Antidepressants: 2169, and
4. Benzodiazepines: 4887

The study ran its results with “adjusted models . . .run separately in strata defined by dementia,” and found that their findings did not differ significantly among the dementia and non-dementia groups.

Given the bad rap the atypicals have taken since 2003, the findings were quite surprising. Compared with atypical antipsychotics, they found that the residents’

risks of death that were higher among those who initiated conventional antipsychotics,** antidepressants and benzodiazepines. We also observed risks of femur fracture that were higher with conventional antipsychotics, antidepressants and benzodiazepines used for anxiety, all compared with atypical antipsychotics. No clinically meaningful differences were observed for risk of pneumonia or heart failure. . . . [emphasis mine]

As recently as February of this year a study compared a conventional antipsychotic, haloperidol (Haldol), with one of the atypicals, risperidone (Risperdal). It found that users of Haldol were two times more likely to die of adverse effects than users of Risperdal.


I am not and never will be an ‘atypical über alles’ kind of girl. Despite their effectiveness in many situations, I have concerns about their adverse side effects, and about some of the hiding of information on the part of certain of the drug companies that produce them.

But, given the findings that the other classes of meds used to treat symptoms of dementia are more dangerous, it’s hard to think the atypicals didn’t get the short end of the public-relations stick, with the first and most memorable FDA warning, the Black Box warning on the insert, and the general belief that they’re the most dangerous game in town.

For really it looks like, as they say in the stock market, they’re ‘the best house in a bad neighborhood.’

It all comes down to the ‘atypical attitude.’


Gill SS, et al. Antipsychotic drug use and mortality in older adults with dementia. Annals of Internal Medicine 2007; 146:775–86.

Huybrechts, K.F. et al Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study. British Journal of Medicine 2012; 344:e977.

Huybrechts KF, et al. Risk of death and hospital admission for major medical events after initiation of psychotropic medications in older adults admitted to nursing homes. Canadian Medical Association Journal 2011; 183(7):E411-E419.

Kales HC, et al. Trends in antipsychotic use in dementia 1999-2007. Archives of General Psychiatry, 2011; 68(2):190-197.

Ventimiglia J, et al. An analysis of the intended use of atypical antipsychotics in dementia. Psychiatry (Edgmont) 2010; 7(11):14–17.

Wang P, et al. Risk of Death in Elderly Users of Conventional vs. Atypical Antipsychotic Medications. New England Journal of Medicine 2005; 353:2335-2341.


*[Note: this was not a randomized trial. Such a set-up is recommended to confirm these findings.]

**[Of note: the findings regarding the relative safety of the atypicals versus the ‘typical’ antispsychotics are nothing new. Just to provide a couple examples: Wang et al conclude in the New England Journal of Medicine: “Conventional antipsychotic medications were associated with a significantly higher adjusted risk of death than were atypical antipsychotic medications at all intervals studied . . .and in all subgroups defined according to the presence or absence of dementia or nursing home residency.” And a 2007 study from the Annals of Internal Medicine found that “the use of conventional drugs seemed to be associated with a higher risk for death than did the use of atypical drugs.”]

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