(June 20, 2017) A pair of new research reports illuminates a striking contrast in the influence of evidence on how providers prescribe specific antipsychotic medications.
On the one hand, FDA box labels - including "black box" labels for severe side effects - appear to be a significant driving force. Peggy L. O'Brien and colleagues analyzed eight years of psychiatric medications by diagnosis, including antipsychotics, to identify how prescribing patterns were influenced by changes to medication box labels. In their analysis, evidence placed on boxes was influential.
On the other hand, despite the well-documented benefits of the antipsychotic clozapine and the poor outcomes associated with "drug cocktails" of multiple antipsychotic medications, Yan Tang and colleagues found that underuse of clozapine for treatment-resistant psychosis and overuse of antipsychotic polypharmacy remain common. In their analysis, evidence was not the deciding factor in prescription practice.
Box Labeling and Practice
O'Brien and colleagues analyzed off-label prescription practices, by diagnosis, for the years 2005-2013 to examine whether changes in box labels on psychiatric medications influence the medications providers prescribe. Off-label prescribing is the use of a medication for a condition not indicated on the box. Uses are added to labels when pharmaceutical companies make application to the FDA with relevant data and receive approval, a costly process that may be a disincentive to improved labeling, according to the authors.
Shortly before 2005, black box labels were added to antipsychotic medications warning about an increased risk of death in older adults with dementia. The authors found the largest decrease in prescriptions for antipsychotics in this and other populations covered by the new warning.
Most antipsychotics in 2005 were labeled for bipolar and psychotic disorders, including schizophrenia. Since then, labeling for a number of antipsychotics has been expanded to include additional age groups and indications (e.g., for the depressive cycle in bipolar, tics associated with Tourette's disorder and irritability associated with autistic spectrum disorders in children). The authors found large increases in antipsychotic prescriptions for depression after the label change and more modest increases for disorders diagnosed before adulthood and for schizophrenia and other psychotic disorders.
The authors additionally analyzed prescription patterns for antidepressants and anti-anxiety drugs and found similar patterns.
"FDA labeling plays a major role in influencing how providers select medications to prescribe for specific conditions," the authors wrote in the Psychiatric Services report.
Efficacy and Practice
In the same issue of Psychiatric Services, Tang and colleagues found a distinctly different pattern in prescriptions for schizophrenia.
The authors analyzed Pennsylvania Medicaid records from 2010-2012 to examine provider patterns in prescribing clozapine and antipsychotic polypharmacy to more than 40,000 patients with schizophrenia. Clozapine is the only medication approved by the FDA for treatment resistance and for reducing suicidal and violent behaviors associated with psychotic disorders. It is considered a best practice. In contrast, simultaneous combinations of two or more antipsychotics ("antipsychotic polypharmacy" in clinical settings or "drug cocktails" in everyday language) lack evidence and are associated with safety concerns and high direct costs. Antipsychotic polypharmacy is considered an indicator of poor quality in care.
Overall, the Tang study found fewer than 1 in 10 providers prescribed clozapine or multiple antipsychotics but identified significant differences between the patterns in different provider types. For example, only 2% of providers with the sickest patients (in the top quartile of schizophrenia-related hospitalization) used antipsychotic polypharmacy, while 16-20% of providers who prescribed no clozapine prescribed multiple antipsychotics, depending on the year.
The authors found that prescribers with larger numbers of Hispanic and non-Hispanic black patients in their practices were less likely to prescribe either clozapine or polypharmacy than providers seeing fewer racial or ethnic minorities; providers whose practices included a higher number of Medicaid-eligible patients were more likely to use one of the practices. Substantial variation in both prescription practices was also found among different managed care plans.
Authors of both studies noted the need for providers to be better informed and responsive to evidence.
"This analysis underscores the need for new approaches to promote evidence-based antipsychotic prescribing to improve outcomes for this population," Tang and colleagues wrote.
Said O'Brien and colleagues, "It is important to ask why off-label uses that are contradicted persist."
Doris A. Fuller
Chief of Research and Public Affairs
References:
- O'Brien, P.L. et al. (June 2017). Off-label prescribing of psychotropic medication, 2005-2013: An examination of potential influences. Psychiatric Services.
- Tang, Yan et al. (June 2017). Prescribing of clozapine and antipsychotic polypharmacy for schizophrenia in a large Medicaid program. Psychiatric Services.
Follow ORPA on Twitter at @TACResearch.
Research Weekly is a summary published as a public service of the Treatment Advocacy Center and does not necessarily reflect the findings or positions of the organization or its staff. Full access to research summarized may require a fee or paid subscription to the publications.
To comment, please visit our Facebook page.