Dementia Drugs Tied to Increased Mortality Risk

Dementia drugs may pose a risk for patient death more than previously understood, according to findings published in JAMA Psychiatry.

Researchers from the University of Michigan Health System retrospectively examined about 45,000 patients aged 65 years or older with a diagnosis of dementia in order to determine mortality risk increase among patients using therapy drugs. Patients who received treatment antipsychotic (haloperidol, olanzapine, quetiapine, and risperidone), valproic acid and its derivatives, or an antidepressant between October 1, 1998 and September 30, 2009 were observed. Then, the researchers compared the mortality of these patients with about 45,000 non-medicated participants. They were compared using the antidepressant group as the reference, and the findings were adjusted for age, sex, years with dementia, presence of delirium, and other clinical and demographic characteristics.

The researchers found that patients with dementia treated with haloperidol had an increased risk of mortality compared to non-medicated matched participants by 3.8%. The number needed to harm (NNH), or the number of patients who receive treatment that would be associated with one death, for haloperidol was 26. Risperidone was the next highest increased risk for mortality at 3.7 with an NNH of 27. This was followed by olanzapine at 2.5% with an NNH of 40 and quetiapine at 2.0% with an NNH of 50.

“The harms associated with using these drugs in dementia patients are clear, yet clinicians continue to use them,” lead author and U-M/VA psychiatrist Donovan Maust, MD, MS, explained in a press release. “That’s likely because the symptoms are so distressing. These results should raise the threshold for prescribing further.”

Patients who used antidepressants had a mortality risk ranging from 12.3% with an NNH of 8 for those who used haloperidol to 3.2% with an NNH of 31 for quetiapine users. The researchers also determined that the atypical antipsychotics (olanzapine, quetiapine, and risperidone) demonstrated a dose response increase in mortality risk — 3.5% greater mortality in the high dose subgroup relative to the lower dose subgroup.

When the investigators directly compared quetiapine to risperidone and olanzapine, they discovered a dose adjusted increased risk of 1.7% and 1.5%, respectively.

“In other words, 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’,” concluded Kales, hinting at prescription writing. The team believes that these practices hinge on the support of policy makers and realignment of reimbursement strategies.