The term “off-label” is a term that has become all too familiar in the drug industry. Simply put it means using a drug to treat something other than what it was approved by the FDA for. But, even though it is common place, is it a safe practice for antipsychotic drugs?
Specifically speaking, in older adults, antipsychotic drugs approved to treat schizophrenia and bipolar disorder, are commonly prescribed off-label. Commonly used antipsychotics are even often prescribed to treat dementia, even though the FDA warns of doing so. And a new study has found that 4 of the commonly used antipsychotics prescribed off label for use in patients over 40 were found to lack both safety and effectiveness.
According to Science Daily, Researchers at the University of California, San Diego School of Medicine, Stanford University and the University of Iowa, and funded by the National Institute of Mental Health looked at four atypical antipsychotics (AAPs) — aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal) — in 332 patients over the age of 40 diagnosed with psychosis associated with schizophrenia, mood disorders, PTSD, or dementia.
“Our study suggests that off-label use of these drugs in older people should be short-term, and undertaken with caution,” said Dilip V. Jeste, MD, Estelle and Edgar Levi Chair in Aging, Distinguished Professor of Psychiatry and Neurosciences, and director of the Stein Institute for Research on Aging at UC San Diego.
Results of the five-year study led by Jeste, who is also current president of the American Psychiatric Association (which was not involved in this research), showed that within one year of treatment, one-third of the patients enrolled in the study developed metabolic syndrome (medical disorders that can increase the risk of cardiovascular disease or diabetes). Within two years, nearly a quarter of the patients developed serious adverse effects and just over half developed non-serious adverse effects.
Because the patients enrolled in the study were all previously diagnosed with psychotic symptoms, no placebo was used in the trial. Instead, the researchers used a technique called “equipoise stratified randomization” which is a hybrid of complete randomization and a clinician’s choice method.
“Our goal was to ensure clinical relevance,” said Jeste. Patients had to agree to be randomized to 2, 3 or 4 of the study drugs, as they or their physicians were allowed to exclude one or two of the study AAPs, due to past experience or anticipated risk of the particular drug. Treating clinicians could determine the optimal dosage.
While the researchers’ intent was to continue the patients on the randomized medications for two years, the average length turned out to be only six months, after which the medications were halted or switched because they didn’t work and/or had side effects.
Because of a notably high incidence of serious adverse events, quetiapine had to be discontinued midway through the trial.
Using a common scale called the Brief Psychiatric Rating Scale (BPRS), to measure symptoms such as delusions, hallucinations, unusual behavior, depression, and anxiety, assessments were made at 6 weeks, 12 weeks, and then every 12 weeks. Results using “blind” raters showed no significant improvement in BPRS over a six-month period.
“While there were a few significant differences among the four drugs, the overall risk-benefit ratio for the AAPs in patients over age 40 was not favorable, irrespective of diagnosis and drug,” said Jeste.
While the researchers say their findings do not suggest that these AAPs should be banned in older patients with psychiatric disorders, they do indicate that considerable caution is warranted in off-label, long-term use of the drugs in older persons.
“When these medications are used off-label, they should be given in low dosages and for short durations, and their side effects monitored closely,” said Jeste. “Clearly, there is also a critical need to develop and test new interventions that are safe and effective in older people with psychotic disorders.”
These results were published November 27 in The Journal of Clinical Psychiatry.
