It was indisputably bad news for the makers of the new, second-generation (or atypical) antipsychotics–a literal black mark on their name.

It was April, 2005, and the FDA issued an advisory that would strike fear into the hearts of any elderly patient whose doctor recommended a trial of the atypicals:

“Public Health Advisory: Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances:

The Food and Drug Administration has determined that the treatment of behavioral disorders in elderly patients with dementia with atypical (second generation) antipsychotic medications is associated with increased mortality. . .Examination of the specific causes of these deaths revealed that most were either due to heart related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).

And as if that wasn’t bad enough, the FDA slammed the second generation antipsychotics with the infamous ‘Black Box Warning. It’s an alert that appears in the package insert for the drugs–the strongest warning the FDA requires–and it lets the public know that the drugs have serious, or even life-threatening, adverse effects.

It seemed unavoidable: Yes, agitated dementia patients often need to be treated with medication in order to be managed–but the government was declaring that the atypical antipsychotics were dangerous.

So by May, 2005, the message was clear:

Utilize any other psychotropic medicines to manage dementia symptoms: The old antipsychotics, the 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), mood stabilizers, antidepressants. Just steer clear of those atypicals.

Who was to know, at that time, that by 2012 the message would be so radically different as to require a complete re-assessment of the safest medicines to use in managing dementia-related agitation and psychosis?

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More than 50% of people with dementia experience some from of the Behavioral and Psychological Symptoms of Dementia (BPSD), with problematic ones, for caregivers, being disinhibition, delusions, agitation, and/or aggression, all potentially leading to violent and inappropriate behavior.

These symptoms are one of the main reasons the elderly are placed in residential care.  In fact, more than 75% of patients in nursing homes have some sort of BPSD (Zaudig).

In their article, “Management of the behavioral and psychological symptoms of dementia,” Hersch and Falzgraf  note:

The prevalence of BPSD in . . .24 hour care settings has been reported to be as high as 90%.

Something needs to be done to manage those experiencing BPSD–to keep them, and those around them, from harm.

Of course, there are always good old-fashioned restraints–but, as members of a civilized, compassionate society, they are clearly a recourse to avoid at all costs.

And there are certain psychosocial interventions, as well. But the research is not definitive about their value in extreme cases.

This is where psychiatric medication becomes a godsend. In “Antipsychotics for the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD),” the authors write:

For decades, the mainstay of treatment for psychosis in dementia have been the so-called “conventional” or first-generation antipsychotics, that have been used since the ‘50s.

So the conventional antipsychotics prevailed, but with uncomfortable, disfiguring and sometimes dangerous side effects–tremors, muscle stiffness, akathisia (the inability to sit still), parkinsonism, tardive dyskinesia (involuntary, repetitive body movements, which often requires immediate discontinuation of the medication), and–most dreaded–neuroleptic malignant syndrome (rare, but potentially fatal, it is manifested by muscle rigidity, fever, and change in mental status)–when the new atypical antipsychotics came out, with a superior side effect profile and, perhaps, even greater effectiveness. . .well, there was a run on the atypical bank.

While it is very difficult to determine how many prescriptions of the atypicals were written specifically for dementia, we do know that by 1999 over 70% of the prescriptions were for conditions other than schizophrenia, its originally approved usage, and a significant chunk were for ‘geriatric agitation’ (see Glick et al).

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Then came the 2005 FDA warning, and atypical usage plummeted in the dementia crowd.

The paper “Trends in antipsychotic use in dementia 1999-2007” estimates that use of atypicals for dementia declined around 27% after the Black Box Warning.

It looked like serious usage of the atypicals for dementia might be in peril, and the numbers of prescriptions began a precipitous decline.

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And then, lo and behold, 3 years later, in June, 2008. . .

A complete turn-around in the view of the relative safety of the atypicals versus other medications in the elderly was beginning to take place. . . .

REFERENCES

Glick ID. Treatment with atypical antipsychotics: new indications and new populations. Journal of Psychiatric Research 2001; 35(3):187-191.

Hersch EC, Falzgraf S. Management of the behavioral and psychological symptoms of dementia. Journal of Clinical Interventions in Aging 2007; 2(4):611-21.

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

Liperoti R, et al. Antipsychotics for the Treatment of Behavioral and Psychological Symptoms of Dementia (BPSD). Current Neuropharmacology 2008; 6(2):117–124.

Zuaidg M. A risk-benefit assessment of risperidone for the treatment of behavioural and psychological symptoms in dementia. Drug Safety 2000; 23(3):183-95.