Patient Contact Reduces Relapse in LAI and Oral Medication Groups

Frequent contact between patients and experienced staff appears to account for an impressively low relapse rate in both arms of a study comparing long-acting injectable (LAI) antipsychotic risperidone and second-generation oral antipsychotics, according to a report published last month in Psychiatric Services in Advance.  

The report by Peter Buckley, M.D., dean of the Medical College of Georgia Regents University in Augusta, and colleagues is a follow-up to an earlier trial that compared the relapse rates of 305 patients with schizophrenia or schizoaffective disorder who were randomly assigned to LAI risperidone or oral second-generation antipsychotics. The results of the PROACTIVE trial (Preventing Relapse Oral Antipsychotics Compared to Injectables Evaluating Efficacy) revealed no significant difference in the overall rate of relapse between the two groups (42 percent of patients in the LAI group relapsed versus 32 percent in the oral medication group) and no significant difference between the groups in time to first relapse.

In the follow-up study published in Psychiatric Services, Buckley and colleagues examined subsequent relapses among patients who had relapsed in PROACTIVE and who continued in treatment, follow-up, or both. The cohort in the follow-up included 298 of the original 305 patients—147 in the LAI group and 151 in the oral medication group.

A total of 32 patients (11 percent of the original cohort of 305) experienced a second relapse—16 in the LAI group and 16 in the oral medication group. Thirteen patients (4 percent of the original cohort of 305) experienced three relapses—five in the LAI group and eight in the oral medication group. There was no statistically significant difference between the two treatments.

“[T]he proportion of patients experiencing subsequent relapses and the time to relapse were strikingly similar between the two treatment groups,” the authors wrote. “Several factors may account for this finding. First—and likely foremost—the biweekly contact with patients in both treatment groups by experienced staff may have mitigated the extent of later relapses overall in this cohort.

“[A]ll patients in both the injectable and oral treatment arms were seen in the clinic every two weeks, … and missed appointments received immediate attention to determine the reason and to reschedule,” they stated. “The contribution of this level of care to the generally low rates of relapse provides indirect evidence that frequent outpatient contact with patients with schizophrenia may itself be a valid relapse-prevention strategy.”

In an interview with Psychiatric News, Buckley noted that what has driven the perceived benefit of injectable medication is the greater assurance that patients are taking their medication. “But in this study, we washed out that benefit because both groups were under the watchful eye of our team,” he said. “What we ended up showing is that when you provide care in a setting where patients are seen frequently, we can really impact relapse.”

John Kane, M.D., who was principal investigator along with Nina Schooler, Ph.D., in the original PROACTIVE trial, told Psychiatric News he continues to believe in the value of LAI antipsychotic medication in reducing relapse and addressing problems related to adherence to treatment. He noted that in the original PROACTIVE trial, the LAI group had significantly greater improvement in psychotic symptoms and total score on the Brief Psychiatric Rating Scale.

“Normally that would be important news, but because we were looking at relapse, it was overshadowed,” Kane said. He is senior vice president for behavioral health services at North Shore Long Island Jewish Health System and chair of psychiatry at Zucker Hillside Hospital.

Moreover, he echoed Buckley that the design of the trial and follow-up—allowing all patients in both arms to be seen regularly in clinic—ensured close monitoring of patients that is less likely to occur in day-to-day practice, where LAI medications may confer a benefit.

Additionally, patients in the oral medication group had the option of changing medications—an effort at “pragmatic” study design, as opposed to the strict protocols of traditional randomized, controlled trials—a choice that was not available to the LAI group.

Kane said naturalistic studies looking at large cohorts of patients that more closely resemble real-world clinical practice—where lack of adherence to medication is a ubiquitous barrier to recovery—have demonstrated the benefits of LAI medication, as have “mirror image” studies, in which a period of oral medication use is followed by a period of LAI.

“I still believe LAI antipsychotics can be very helpful in reducing relapse,” Kane said. “The challenge is how you go about studying it.” ■