Long-acting, injectable formulations of antipsychotic drugs significantly boosted treatment compliance in patients with schizophrenia in a review of reimbursement records for more than 3,600 patients.

The increased compliance achieved with depot administration of antipsychotic medications makes it an attractive alternative to oral administration of antipsychotic drugs to patients with schizophrenia, Dr. Bruce J. Wong said at the meeting.

Mitchel L. Zoler/IMNG Medical Media

Dr. Bruce J. Wong

Greater use of depot medications could improve the management of patients with schizophrenia because treatment compliance is a major determinant of the ongoing health of schizophrenia patients, said Dr. Wong, a consultant clinical epidemiologist in Wayne, Pa.

“Lack of patient adherence to psychotropic medications is the single largest factor contributing to the ongoing morbidity of schizophrenia today. Even short gaps in antipsychotic usage increase the risk of rehospitalization” of patients, said Dr. Wong, also of the department of biostatistics and epidemiology at the University of Pennsylvania, Philadelphia.

“In practice today, depot, injected antipsychotic medications are secondary treatments, used almost like punishment when patients are noncompliant with oral drugs but should be viewed more like a reward,” he said. The same drugs are formulated into oral and injectable preparations, so depot versions are not less effective or less safe than oral forms. Instead, a series of social factors relegate injectable formulations to second-line status: needle phobia in patients, a modest amount of pain that can occur when antipsychotic drugs are injected into muscle, the lack of comfort that psychiatrists often have with performing injections, and the need for a psychiatrist to obtain and have the drug on hand as opposed to the convenience of writing a prescription for the patient to get the oral form.

None of these alone is a major barrier, but together they seem to create enough of a roadblock to make injections less favored, Dr. Wong said in an interview.

To better document how the two delivery options relate to compliance, Dr. Wong and his associates used data collected on 3,004 commercially insured patients with schizophrenia in the MarketScan database of Thompson Reuters, and on 665 Medicare patients collected by the Center for Medicare and Medicaid Services during January 2005 to September 2010. The analysis focused on patients who began treatment with either an oral or a long-acting injected formulation of an antipsychotic drug, and who had at least 12 months of continuous health coverage prior to the index prescription.

In the commercial group, 13% of patients received an incident prescription for an injectable formulation, and 87% received an incident prescription for an oral antipsychotic. In the Medicare group, 22% filled a first-time prescription for a depot, injected formulation, and 78% fell into the oral group.

During follow-up, the researchers measured compliance by the average level of patients’ medication possession ratio. For patients taking an oral drug, this was determined by how many days during follow-up patients had their prescribed medication based on their history of filling their prescription. For patients receiving an injected drug, Dr. Wong and his associates calculated a medication possession ratio based on the frequency at which a patient’s records documented receiving an injection, and the number of days the injection covered during follow-up.

Among commercially insured patients, those who received injections had an average 67% medication possession ratio, compared with a 56% rate among patients taking an oral drug. In the Medicare group, injected patients had a 68% possession ratio, compared with 59% in those on an oral drug. In both subgroups the difference in ratios between the two types of treatment were statistically significant.

The analyses also identified other differences between the two treatment groups. Among the commercially insured, injected drugs were significantly more common than oral drugs in patients treated in comprehensive health plans, while injected drugs were used significantly less often than oral drugs in health maintenance organization settings.

Among commercially insured patients, those who received long-acting injections averaged 42 years old, significantly older than those who received oral drugs, who averaged 37 years old. Dr. Wong attributed this age difference to patients typically starting on an oral formulation and only switching to an injected formulation a few years later, once they showed that they were not reliable oral users. Medicare patients also showed a significant age difference, but the relationship flipped in this older age group. The mean age of the patients on injected antipsychotics was 67, while those on an oral drug averaged 73 years old. Dr. Wong said he did not have an explanation for this pattern among Medicare patients.

In the commercial group, patients on injected drugs were also significantly sicker, with an average Charlson comorbidity index of 0.58, compared with an average of 0.47 in the orally treated patients. Again, this pattern was reversed in Medicare patients, where the injected patients had an average Charlson comorbidity index score of 1.24, significantly less than the 1.83 average among patients on an oral drug.

The analysis also showed regional differences in the use of the two treatment options, with injections exceeding oral drug use in the North-Central U.S. region, while oral drugs were substantially more popular than injected drugs in the Western half of the United States. In other U.S. regions, the use of the two treatment routes was generally more balanced.

The study was sponsored by Otsuka, which markets the antipsychotic drug aripiprazole. Dr. Wong said he has been a consultant to Otsuka.