SAN ANTONIO – Older adults with bipolar disorder who receive antipsychotic agents are at increased risk for death, compared with those who received the mood stabilizer valproate, investigators reported at the annual meeting of the American Association for Geriatric Psychiatry.
A review of Veterans Affairs data on 4,854 patients aged 65 and older with bipolar disorder showed that the risk of death within 180 days of receiving an antipsychotic prescription was highest for haloperidol, followed by risperidone, olanzapine, and quetiapine; valproate was associated with the lowest excess risk, according to Dr. Sachin J. Bhalerao, a second-year psychiatry resident at the University of Michigan, Ann Arbor, and his colleagues.
"Although antipsychotics are FDA approved for use in bipolar disorder (unlike with the neuropsychiatric symptoms of dementia), our data indicate that they should be used judiciously when traditional mood stabilizers and psychosocial interventions and psychotherapies do not fully address the patient’s needs," they wrote in a poster presentation.
The investigators looked at VA data on 4,854 adults 65 and older with a new medication start of haloperidol, risperidone, olanzapine, quetiapine, or valproate, no history of antipsychotic or anticonvulsant use in the previous year, monotherapy during 180-day follow-up, and for valproate users, no concurrent seizure disorders.
About one-third of the sample (35.1%) took valproate, followed by quetiapine (23%), risperidone (21.2%), olanzapine (17.9%), and haloperidol (2.8%). Although the demographics of the various drug groups were generally similar, the haloperidol group had a higher proportion of African Americans and unmarried people than the other groups. Patients on haloperidol also had more medical comorbidities than others, as well as higher rates of comorbid dementia, delirium, and substance abuse.
During 6-month follow-up, there were 21 deaths among 137 patients on haloperidol (15.3%), 68 among 1,027 on risperidone (6.6%), 43 among 868 on olanzapine (5%), 29 among 1,119 on quetiapine (2.6%), and 38 among 1,703 on valproate (2.2%).
In covariate-adjusted exposure and intent-to-treat models, the relationship between drug type and mortality remained essentially the same, with haloperidol users at highest risk (relative risk, 1.31), followed by risperidone (reference), olanzapine (RR, 0.75), valproate (RR, 0.42), and quetiapine (RR, 0.28).
Although the mechanism by which antipsychotic agents might increase the risk of death in the elderly is unknown, "a growing body of evidence suggests that antipsychotics increase mortality risk in both elderly dementia and nondementia populations," the investigators wrote. "This may be interpreted to indicate that the link to mortality in these conditions has less to do with the particular psychiatric condition or underlying brain pathology (for example, in dementia) and more to do with age and associated medical comorbidity."
The study was supported by a National Institute of Mental Health grant to principal investigator, Dr. Helen C. Kales. The authors had no conflict of interest disclosures.