by Leslie Citrome, MD, MPH; Zhenchao Guo, PhD; Iftekhar Kalsekar, PhD; Robert A. Forbes, PhD; and Tony Hebden, PhD
Dr. Citrome is with the Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, New York; Drs. Kalsekar, Guo, and Hebden are with Bristol-Myers Squibb, Plainsboro, New Jersey Dr. Forbes is with Otsuka Pharmaceutical Development and Commercialization, Princeton, New Jersey.

Innov Clin Neurosci. 2012;9(3):17–18

Funding: This study was supported by Bristol-Myers Squibb.

Financial Disclosures: Dr. Citrome is/was a consultant for, has received honoraria from, or has conducted clinical research supported by the following: Alexza, Alkermes, AstraZeneca, Avanir, Bristol-Myers Squibb, Eli
Lilly, Janssen, Lundbeck, Merck, Novartis, Noven, Pfizer, Shire, Sunovion, and Valeant. Drs. Kalsekar, Guo, and Hebden are employees of Bristol-Myers Squibb Company; and Dr. Forbes is with Otsuka Pharmaceutical
Development and Commercialization.

Key words: Antipsychotic, bipolar disorder, combination therapy, commercially insured, depression, outpatient, schizophrenia

Abstract: In this data snapshot, the IMS PharMetrics Database was examined to assess the prevalence of combination antipsychotic therapy for the years 2003 through 2009 among 122,349 commercially insured adult individuals with bipolar disorder, depression, or schizophrenia. Although all three diagnostic groups were associated with varying amounts of combination antipsychotic use that included aripiprazole, olanzapine, quetiapine, risperidone and ziprasidone, persons with schizophrenia exhibited the highest rates. These findings indicate that from the perspective of “practice-based evidence,” providers see value in combination therapy.

Data Snapshot

Combinations of antipsychotics are prescribed in clinical practice, with the assumption that severely ill or treatment-refractory patients may require this treatment approach[1] despite the lack of supporting data from randomized, controlled, clinical trials.[2] In the current study, we explored the use of combination antipsychotic treatment in commercially insured outpatients with depression, bipolar disorder, or schizophrenia. This differs from prior published pharmacoepidemiological studies that have focused on persons with schizophrenia only,[3] inpatients,[4] and/or those covered by Medicaid.[5]

The IMS PharMetrics Database, which contains patient-level medical and pharmacy claims for over 30 million covered lives from approximately 25 commercial health plans in the United States, was examined to assess prevalence of combination antipsychotic therapy. Annual data from 2003 through 2009 for all adult patients (18–64 years of age) receiving first-line, second-generation antipsychotic (SGA) medication (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone) were examined. A total of 122,349 individual patients were included in this analysis. Patients were categorized by diagnosis (bipolar disorder, n=32,202; depression, n=85,701; and schizophrenia, n=4,446).
Combination antipsychotic therapy was defined as an overlap of more than 50 percent of cumulative medication days regardless of dose during a one-year period, including both SGAs and first-generation antipsychotics.

Figures 1A–C describe the percentage of patients receiving combination therapy by SGA of interest by year. The largest percentages of patients receiving combination antipsychotic treatment were those with schizophrenia.

Limitations to our data snapshot include the possibility that subjects may have received medications not captured in the database (e.g., in the form of samples, coupons or prescriptions filled out-of-pocket, or through another insurer). Overlap of prescriptions may represent a cross-titration from one antipsychotic to another, a process that can be lengthy.

In the current study, we found evidence of combination antipsychotic therapy in patients with depression, bipolar disorder, and schizophrenia, with the highest prevalence observed in the latter group. These findings indicate that from the perspective of “practice-based evidence,” providers see value in combination therapy. Future studies are required to delineate the patient populations that are receiving combination therapy and to determine whether this treatment approach offers any benefit over monotherapy.

1. Citrome L, Jaffe A, Levine J. Monotherapy versus polypharmacy for hospitalized psychiatric patients. Am J Psychiatry. 2005;162:631.
2. Citrome L. Treatment-refractory schizophrenia: What is it and what has been done about it? Neuropsychiatry. 2011;1: 325–347.
3. Xiang YT, Wang CY, Si TM, et al. Antipsychotic polypharmacy in inpatients with schizophrenia in Asia (2001–2009). Pharmacopsychiatry. 2012;45:7–12.
4. Jaffe AB, Levine J. Antipsychotic medication coprescribing in a large state hospital system. Pharmacoepidemiol Drug Saf. 2003;12:41–48.
5. Gilmer TP, Dolder CR, Folsom DP, et al. Antipsychotic polypharmacy trends among Medicaid beneficiaries with schizophrenia in San Diego County, 1999–2004. Psychiatr Serv. 2007;58:1007–1010.