The U.S. Food and Drug Administration (FDA) has not

approved any drug for treating the behavioral symptoms

of dementia.

However, atypical antipsychotics are commonly used for

off-label treatment.

In April 2005, the FDA issued A Black Box WarningA Black Box Warning that

the use of atypical antipsychotics to treat behavioral

disturbances in patients with dementia was associated with

greater mortality.

Another FDA black box warning for conventional

antipsychotics followed in June 2008.

Information about mortality associated with individual

antipsychotic agents in patients with dementia is

limited.

In a 2005 meta-analysis of randomized placebo-controlled

trials, no greater risk of death was observed with any

individual atypical antipsychotic.

A study comparing the most frequently prescribed

antipsychotic drugs in Canada found higher 180-day higher 180-day

mortality ratiosmortality ratios for haloperidol and loxapine, but no

difference between olanzapine and risperidone.

The most recent study, using case-control methodology,

found that patients with dementia taking haloperidol,

olanzapine, and risperidone, but not quetiapine, had

short-term increases in mortality compared with patients

who were not taking these agents.

The use of antipsychotics to treat the behavioral symptoms of dementia is associated with greater mortality.

The authors examined the

mortality risk of individual agents to augment the limited information on individual antipsychotic risk.

The authors conducted a retrospective cohort study using national data from the U.S. Department of Veterans Affairs (1999–2008) for:1) The total sample included 33,60433,604

patients.

2)2) Dementia patients age Dementia patients age 65 and older65 and older 3) Began outpatient treatment with an

antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) or valproic acid (as a nonantipsychotic comparison).

4) Individual drug groups were compared for 180-day mortality rates180-day mortality rates.

HaloperidolHaloperidol was associated with the highest mortality rates.

Followed by risperidon, olanzapine, valproic acid and its derivatives, and finally, quetiapine.

The mortality risk with haloperidol was highest in the first 30 days but decreased significantly and sharply thereafter.

Among the other agents, mortality risk differences were most significant in the first 120 days and declined in the subsequent 60 days during follow-up.

HaloperidolHaloperidol had 1.5 times the risk of mortality of other psychotropics in patients with dementia.

Risperidone, valproic acid and derivatives, and olanzapine had intermediate risk, and quetiapinequetiapine had the lowest risk.

QuetiapineQuetiapine was prescribed in lower doses, often for less ill patients, but was associated with increased parkinsonian symptoms.

Haloperidol was more frequently prescribed by nonpsychiatrists and more often in older, medically ill African Americans.

The increased risk of haloperidol was primarily in the first 30 days.

The effcacy of quetiapine in the behavioral disturbances associated with dementia is questionable, whereas risperidone and olanzapine have signifcant benefcial effects and therefore would be preferred for treatment.

The use of valproic acid and derivatives as alternative agents to address the neuropsychiatric symptoms of dementia may carry associated risks as well.