Maintenance treatment with long-acting injectable risperidone in first-episode schizophrenia: a randomized effectiveness study

Abstract

Background: Because long-acting injectable (LAI) antipsychotics are largely reserved for persistently ill patients, little is known about the use of LAIs early in the course of illness for first-episode outpatients.

Method: A prospective, open-label, randomized controlled trial was conducted in which outpatients with first-episode DSM-IV schizophreniform disorder, schizophrenia, or schizoaffective disorder were enrolled from December 2004 to March 2007. Participants were randomly assigned at a 2:1 ratio to a recommendation of changing to LAI risperidone microspheres (RLAI) (n = 26) or continuing oral antipsychotic treatment (n = 11) for up to 104 weeks. Primary outcomes were time until initial nonadherence (medication gap of ≥ 14 days) and medication attitudes as assessed with the Rating of Medication Influences scale. Patients randomly assigned to an RLAI recommendation could decline the recommendation, so analysis defined treatment groups by intent-to-treat and as-actually-treated.

Results: Eighty-one percent of patients (30/37) stopped medication within 104 weeks. There was a trend toward an initial adherence benefit favoring RLAI acceptors at 12 weeks (P = .058), but no significant difference between RLAI and oral antipsychotic treatment in time to initial nonadherence during the overall study (P = .188). Medication attitudes did not differ between groups.

Conclusions: Acceptance of RLAI was associated with an initial adherence benefit that was not sustained over time. Early introduction of LAI therapy did not adversely affect adherence attitudes. The small size of the study and low power limit interpretation, but the few patients who remained adherent into a second year were all receiving RLAI. Nonadherence was almost universal in our first-episode cohort, but nonadherence was more easily detected among first-episode patients treated with LAI therapy than it was with oral antipsychotics.

Trial registration: ClinicalTrials.gov identifier: NCT00220714.