Physicians often prescribe antipsychotic drugs to older people with dementia to control non-memory related behavioral symptoms, including agitation, aggressiveness, delusions and hallucinations.

But officials at the U.S. Food and Drug Administration (FDA) have never approved antipsychotic medications — such as haloperidol (Haldol), risperidone (Risperdal), olanzapine (Zyprexa) and quetiapine (Seroquel) — for that purpose. Indeed, these medicines come with a “black box” FDA warning that their use to control behavioral disturbances in people with dementia is associated with an increased risk of premature death.

Many physicians have continued to prescribe the drugs to their patients with dementia anyway, believing that the benefits — primarily protecting patients from harming themselves or others — outweigh the risks.

A study published Wednesday in the journal JAMA Psychiatry, however, presents troubling new evidence that those risks are significantly higher than previously reported.

A VA database

For the study, researchers from the University of Michigan, the University of Southern California and the Veterans Administration analyzed medical data of almost 91,000 U.S. veterans (mostly men) aged 65 and older with diagnosed dementia. Approximately half the patients had been treated for behavioral problems with an antipsychotic, anticonvulsant (valproic acid) or antidepressant medication; the other half didn’t receive any of these drugs.

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After crunching the data, the researchers found that veterans who were given antipsychotic medications had a risk of dying significantly higher than those not taking the medications. For example, 20.7 percent of the patients taking haloperidol died within six months — 3.8 percent more than the non-users. Among the patients taking quetiapine, 11.8 percent died within six months — 2.0 percent more than the non-users. The increased risk of death for the olanzapine and risperidone patients fell somewhere between.

These risks are two to four times higher than previously cited in the medical literature, the study’s authors point out.

The new analysis also revealed that the higher the dose of an antipsychotic medication, the greater the risk of premature death.

Another troubling finding was that people prescribed haloperidol — the riskiest of the drugs — were more likely to be unmarried, African-American or living in facilities with fewer beds for patients.

As for the two other types of drugs used to treat behavioral problems in people with dementia — valproic acid and antidepressants — the researchers found that the increased risk of premature death associated with the anticonvulsants was not statistically significant and the increased risk associated with the antidepressants was only slightly higher than for non-users.

Number needed to harm

Another way of assessing the risk from the antipsychotic medications is with an epidemiological measurement tool known as the “number needed to harm” (NNH). In this study, the NNH reflects the number of older adults with dementia who would have to be taking a particular drug for one of them to die within six months.

For the haloperidol users in the study, the NNH was 26. In other words, for every 26 patients with dementia taking haloperidol, one would be expected to die within half a year. Risperidone was only slightly less risky, with an NNH of 27. For olanzapine the NNH was 40, and for quetiapine it was 50.

By comparison, the NNH in this study for antidepressant use was 166. (There’s little evidence, however, that antidepressants are effective for patients with dementia.)

Time to raise the threshold

Earlier this month, federal investigators with the Government Accountability Office (GAO) issued a report in which they cited evidence of the widespread overuse of psychiatric drugs in older Americans with dementia.

In 2012, about one-third of older adults with dementia who spent at least 100 days in long-term nursing home and about 14 percent of those living outside a nursing home were prescribed an antipsychotic medication, the report noted.

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“The harms associated with using these drugs in dementia patients are clear, yet clinicians continue to use them,” said Dr. Donovan Maust, the lead author of the JAMA Psychiatry study and a geriatric psychiatrist at the University of Michigan and the VA Center for Clinical Management Research, in a released statement.

“That’s likely because the symptoms are so distressing,” he added.“These results should raise the threshold for prescribing further.”

Maust says the emphasis on treating behavioral problems in older people with dementia should focus on non-drug strategies first. But, of course, those strategies take more time and are not always fully reimbursed by Medicare or private health insurance.

“Non-pharmacologic approaches will only succeed if we as a society agree to pay front-line providers for the time needed to ‘do the right thing,’ ” said one of Mast’s co-authors, Dr. Helen Kales, in the released statement.

Unfortunately, the JAMA Psychiatry study is behind a firewall at the journal’s website, despite the fact that it was funded in large part by taxpayer money through the National Institute of Mental Health and the National Institute on Aging.

You can read the GAO report on the overprescribing of antipsychotic medications at that agency’s website.