APA: Dosing Schedule Doesn't Matter for Antipsychotic Drug Adherence

SAN DIEGO, May 21 -- Frequency of dosing of antipsychotic agents does not appear to affect medication adherence in most patients with schizophrenia, reported investigators here.

Patients who are stable on an antipsychotic agent are just as likely to adhere to their regimen whether the drug is prescribed once or twice daily, according to Paul Pfeiffer, M.D., and colleagues of the VA Center for Practice Management and Outcomes Research and the University of Michigan, both in Ann Arbor.

But patients who have a big increase in their dose and a change in dosing frequency may have more difficulty adhering, they said at the American Psychiatric Association meeting.

After a dose increase of 50% or more, there was a significant drop in adherence rates among patients who had been on once-daily dosing but were moved to a twice-daily or more schedule, the authors found in a study of 32,000 patients.

"Antipsychotic medications are effective in the treatment of schizophrenia," they wrote. "However, partial adherence is common and is associated with increased hospitalization. Medication dosing schedule may influence adherence rates and is an inexpensive and modifiable target for intervention."

The researchers first identified patients with a diagnosis of schizophrenia from the VA National Psychosis Registry, and then linked the data with a VA pharmacy database to identify those who, during fiscal year 2005, had been on haloperidol or an atypical antipsychotic, excluding clozapine (Clozaril), with no change in dosing schedule.

The researchers then assessed adherence by calculating a medication-possession ratio, the ratio of the supply of drug filled by the pharmacy to the supply needed for continuous use. They calculated mean medication-possession ratios for each group using the Mann-Whitney-Wilcoxon test and multivariate linear regression analyses.

A total of 23,157 patients were on once-daily meds, and 9,399 were on more-than-once daily dosing. The investigators found no significant differences in characteristics between the groups in bivariate analyses, and no significant difference in mean medication possession. Both groups had a mean ratio of 0.80 + 0.32 (P=0.0572).

In a second analysis, the authors looked at a group of 5,358 patients who had been on a once-daily regimen and had a dose increase of 50% or more during fiscal 2005. Of these patients, 1,653 had sufficient data on before-and-after dose increase to calculate a medication possession ratio. A total of 1,391 had a dose increase but remained on a once-daily schedule, while 262 had a change to twice-daily or more dosing.

There was no significant difference between the groups before the dose increase, but those patients who had an increase in dosing frequency had significantly lower adherence after the increase.

Among the patients who stayed on once-daily dosing, the adherence ratio before the increase was 0.92 + 0.32, compared with 0.88 + 0.39 for those on twice daily dosing pre-increase (P=0.12). But after dosage increase, the adherence rate stayed virtually the same among those who kept to the once-daily schedule (0.91 + 0.38), but it was significantly lower among those who were bumped up to two or more doses per day (0.79 + 0.31, P vs. once-daily <0.0001).

"Less stable patients may have more difficulty with more than once-daily dosing schedules," the investigators wrote. "Alternatively, these differences may be caused by unmeasured factors, such as higher levels of side effects, among those patients moving to more than once per day dosing schedules."