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NEW YORK CITY -- Schizophrenia patients who had recently been released from jail were less likely to be re-arrested or otherwise fail treatment when they took a depot antipsychotic drug compared with daily oral medication in a randomized trial, a researcher reported here.

Among 444 patients participating in the study, those assigned to paliperidone palmitate (Invega Sustenna) had a median time to treatment failure -- defined as arrest or incarceration, psychiatric hospitalization, discontinuation of treatment, supplementation with another antipsychotic, or needing extra services to prevent imminent psychiatric hospitalization -- of 416 days (95% CI 285 to no upper bound), compared with 226 days (95% CI 147-304, P=0.011) for patients taking any of seven first- or second-generation oral antipsychotics chosen at the treating clinician's discretion.

Arrests and incarcerations were the most common reasons for treatment failure, and a reduction in these events accounted for most of the difference between study arms, according to , of Janssen Scientific Affairs in Titusville, N.J., who reported the findings at the American Psychiatric Association's annual meeting.

Janssen manufactures paliperidone palmitate and funded the study. Starr said it was the first prospective, controlled trial ever to examine a depot drug specifically in a criminally recidivist population. To represent the real-world population for which depot drugs are primarily intended even more accurately, it also included many patients who had comorbid substance use disorders.

Of the 207 patients in the trial who met the criteria for a first treatment failure, 112 of them were arrested or jailed, including 64 in the 218-patient oral drug arm versus 48 among the 226 patients given the depot drug.

There were also eight fewer patients receiving depot paliperidone who needed psychiatric hospitalization, and eight fewer who stopped treatment because of inadequate efficacy.

, of New York Presbyterian Hospital and Weill Cornell Medical College in New York City, said the findings were very important and supported a role for depot antipsychotics in patients at high risk for noncompliance with daily oral drugs.

She said that if any criticism could be leveled at the study, it was that its definitions of treatment failure were too stringent.

Anthony pointed out that patients who "failed" because they needed a second drug or more services to prevent hospitalization were still in treatment, which is not a bad thing.

Study Details

To be included in the study, patients had to have been released from jail or prison within 90 days of screening and to have at least two criminal detentions in the past 2 years, one of which must have led to formal incarceration.

They also had to qualify for a schizophrenia diagnosis confirmed by the Mini International Neuropsychiatric Interview.

Exclusion criteria were few. Patients with substance abuse issues were accepted into the study, which Anthony said was another good feature of the study insofar as it was intended to sample a real-world population.

The statistical analysis for efficacy covered all patients who received at least one dose of their assigned drug. Those in the oral drug arm could receive up to six of the following: haloperidol, perphenazine, risperidone (Risperdal), olanzapine (Zyprexa), aripiprazole (Abilify), quetiapine (Seroquel), or paliperidone for daily oral treatment (Invega).

Mean patient age was about 38 and nearly 90% were male. About 60% were African American; most of the rest were white. More than 80% had a duration of psychiatric illness lasting more than 5 years. Patients had a mean history of about six psychiatric hospitalizations, and the mean time since release from custody was about 6 weeks.

Time to treatment failure was the study's primary endpoint. In addition to the median time to failure, Starr and colleagues expressed the main result in two other ways. The hazard ratio for treatment failure was 1.43 (95% CI 1.09-1.88), and the proportions of each arm meeting the criteria for failure were 39.8% for the depot drug and 53.7% for oral medications.

Looking only at time to arrest/incarceration or psychiatric hospitalizations as endpoints, the researchers found essentially the same result. No median time to failure by these criteria was reached in the paliperidone palmitate arm with 450 days of follow-up; in the oral drug group, the median was about 270 days.

On the other hand, safety results did not favor the depot drug. Some 24% of patients receiving the depot drug experienced prolactin-related adverse effects emerging during the trial, such as erectile dysfunction and diminished libido in men and amenorrhea or galactorrhea in woman, versus 4% of patients in the oral drug arm.

Insomnia, akathisia, anxiety weight increase, and, of course, injection site pain were also more common with the depot product and were seen in at least 10% of patients receiving it.

Also, the findings suggested that the efficacy difference between groups was concentrated in the 40% of patients who did not have a comorbid substance use problem.

In those patients, about 65% avoided all the treatment-failure events through the 450-day follow-up, versus about 40% of the oral drug arm.

The difference was much smaller and not statistically significant in the 60% of participants who had substance use disorders. At day 450, treatment failure rates stood at about 37% and 33% for the depot and oral drug groups, respectively.

Implications

"This study really has important public health implications," said , chief medical officer of the Department of Behavioral Health in Washington, D.C., a city with its share of recidivist offenders who have serious psychiatric illnesses.

"In many systems, it is hard for patients who get 3 days of medications when they leave. For example, in Washington, D.C., they're often discharged from jail and they run out of medications and they are very quickly either re-incarcerated or are brought back to the hospital emergency room and are hospitalized."

Ritchie noted that this pattern has economic implications for localities since they end up footing the bill for these preventable incarcerations and hospitalizations.

She acknowledged that many of those receiving the depot drug still ended up back in the criminal justice system or the hospital during the study. "It means we don't have perfection yet," she said, adding that many of these patients face difficult circumstances.

The difference in outcomes in the study was not only statistically significant but important from a clinical and public health standpoint, Ritchie maintained.

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