One of the most important goals in the treatment of people with schizophrenia is preventing relapses, which often lead to periods of hospitalization.

One common cause of the destabilization seen in many relapses is patients' non-adherence to antipsychotic medication. Psychosis, a major debilitating symptom of schizophrenia, can result in delusions, hallucinations, paranoia, or disordered thought. One recent study showed that 35% of patients admitted for a first hospitalization had stopped taking medication within 30 days of discharge, and 54% within 60 days.

The return to the hospital that such non-adherence necessitates can cost patients dearly, not only in terms of emotional suffering but also because second episodes of psychosis in the same individual tend to respond less well to same treatment used in the first episode.

With this fact in mind, a team led by John M. Kane, M.D., a 1992 BBRF Lieber Prize winner at Zucker Hillside Hospital, set out to test a way to increase adherence to antipsychotic medication in newly diagnosed or early-stage schizophrenia patients, using a long-acting injectable form of the antipsychotic aripiprazole.

Although the evidence is not entirely clear, many practitioners believe one way of keeping patients on an antipsychotic regimen is to reduce the number of times the drug must be taken in order to maintain stability.

The team, which included Delbert Robinson, M.D. a 2005 BBRF Independent Investigator, Christoph U. Correll, M.D., a 2007 BBRF Young Investigator, and Nina R. Schooler, Ph.D., a BBRF Scientific Council member and 1998 Distinguished Investigator, recruited 489 early-stage schizophrenia patients, aged 18-35. Three-fourths were men and the average age of the cohort was 25. Forty-six percent of the subjects had 1 year or less of prior antipsychotic use.

In order that the study treatment modeled usual clinical care, the team decided to randomize treatment by clinic. Clinics were randomly assigned to either 1) offer participants treatment with long-acting aripiprazole or 2) provide treatment to their participants based upon the clinic staff’s best clinical judgment. All participants at a particular clinic received the same treatment. Nineteen clinics with a total of 234 participants were randomized to offer long-acting aripiprazole treatment and twenty clinics with a total of 255 participants were randomized to offer clinician choice treatment.

Participants were followed for 2 years. They were interviewed by telephone every other month to obtain data on hospitalizations and emergency/crisis unit use. Every 4 months they completed a medical service-use form; data were checked against medical records where available. Overnight stays in crisis stabilization units and in psychiatric emergency departments were regarded as hospitalizations. Admissions related to substance detoxification were not, for purposes of the study.

Use of a long-acting antipsychotic produced a 44% reduction in the incidence rate of first hospitalizations compared with use of antipsychotics as conventionally delivered. According to the team, which reported results in JAMA Psychiatry, for every 7 patients treated with the long-acting form of antipsychotic medication, 1 hospitalization was prevented, on average.

"Many attribute the low rate of long-acting injectable antipsychotic medications in clinical practice to patient refusal," the team said. But their trial, they said, "demonstrates that with proper training, practitioners are able to communicate potential advantages of long-acting injectables, even in early illness stages, and engage patients in shared decision-making resulting in high acceptance rates."

"It is human nature to have difficulty taking medication on a long-term basis," the researchers acknowledged. "The phenomenon of non-adherence needs to be normalized and de-stigmatized." They suggested that results of their trial suggested one potential way to move toward these objectives.