A randomized controlled trial of long-acting injectable risperidone vs continuation on oral atypical antipsychotics for first-episode schizophrenia patients: initial adherence outcome.

Nonadherence for first-episode schizophrenia is a major unsolved challenge. The long-acting injectable route is an appealing strategy, but there are concerns about acceptability. We report on acceptance and initial adherence outcomes with risperidone long-acting injection (RLAI) in first-episode schizophrenia patients. We conducted a prospective randomized controlled trial in which we enrolled patients defined by appropriate Structured Clinical Interview for DSM-IV diagnosis and < or = 16 weeks of lifetime antipsychotic exposure. Participants were randomly assigned (2:1 ratio) to a recommendation of changing to RLAI versus continuing on oral therapy (ORAL). Nonadherence behavior was defined as a medication gap > or = 14 days. Adherence attitudes were determined by the Rating of Medication Influences (ROMI) scale. A priori analysis defined treatment groups as intent-to-treat (ITT) and as-actually-treated (AAT) for the first 12 weeks after initial randomization. Participants were enrolled from December 2004 to March 2007. Of 46 eligible patients, 37 were randomly assigned, 11 to ORAL and 26 to RLAI. Nineteen of 26 patients (73%) accepted the RLAI recommendation. There were no differences in adherence behavior at 12 weeks based on initial randomization (Kaplan-Meier survival for ITT: 76% [95% CI, 35%-90%] adherent for RLAI vs 72% [95% CI, 55%-89%] for ORAL; log-rank P = .78), but patients accepting RLAI were significantly more likely to be adherent than patients staying on ORAL (AAT: 89% [95% CI, 64%-97%] adherent for RLAI vs 59% [95% CI, 32%-78%] for ORAL; log-rank P = .035). There were no ROMI attitude differences between either treatment group comparison at 12 weeks. Most first-episode patients taking oral antipsychotics will accept a recommendation of RLAI therapy. On the basis of initial randomization status, an RLAI recommendation did not affect adherence behavior at 12 weeks. However, acceptance of RLAI was associated with significantly better adherence. Regardless of whether RLAI is recommended or accepted, there is no adverse impact on subsequent medication attitudes at 12 weeks. These results support the feasibility and acceptability of introducing RLAI as a treatment option for first-episode schizophrenia patients. clinicaltrials.gov Identifier: NCT00220714.

Weiden PJ ，Schooler NR ，Weedon JC ，Elmouchtari A ，Sunakawa A ，Goldfinger SM ... -  《-》

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

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. 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. 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. 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. ClinicalTrials.gov identifier: NCT00220714.

Weiden PJ ，Schooler NR ，Weedon JC ，Elmouchtari A ，Sunakawa-McMillan A ... -  《-》

Oral versus injectable antipsychotic treatment in early psychosis: post hoc comparison of two studies.

Few studies have compared long-acting injectable second-generation antipsychotics with oral antipsychotics. Long-acting injectable antipsychotics-developed specifically to address the problem of adherence-might have an important role to play in treating early psychosis. The effects of oral antipsychotics versus risperidone long-acting injection (RLAI) were compared between 2 similar studies lasting 2 years each that were conducted at our site in South Africa. Results of an open-label study in which patients were treated with flexible doses of RLAI were compared with the results of a randomized controlled trial of flexible doses of oral risperidone or haloperidol. Inclusion criteria for both studies were age 16 to 45 years; confirmed diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder; <or=2 hospitalizations for psychosis; and lifetime exposure to <or=12 weeks of antipsychotic medication. The dose of RLAI was 25 mg every 2 weeks, which could be increased to 50 mg. Doses of oral risperidone or haloperidol began at 1 mg/d and were increased if necessary up to a maximum dose of 4 mg/d (8 mg/d in exceptional cases). Study assessments included the Positive and Negative Syndrome Scale (PANSS), the Extrapyramidal Symptom Rating Scale (ESRS), and body mass index (BMI). The RLAI group included 50 patients (32 men and 18 women; mean [SD] age, 25.4 [7.4] years; BMI, 20.6 [4.6] kg/m(2)). The oral risperidone or haloperidol group included 47 patients (27 men and 20 women; mean [SD] age, 25.9 [5.8] years; BMI, 20.1 [3.4] kg/m(2)). Compared with patients treated with oral risperidone or haloperidol, RLAI-treated patients had significantly fewer all-cause discontinuations (26.0% [13/50] vs 70.2% [33/47] at 24 months; P < 0.005), greater reduction on the PANSS total score (-39.7 vs -25.7; P = 0.009), higher remission rate (64.0% [32/50] vs 40.4% [19/47]; P = 0.028), and lower relapse rate (9.3% [4/43] vs 42.1% [16/38]; P = 0.001) among the responders. Extrapyramidal symptoms were significantly lower in the RLAI group than in patients treated with oral risperidone or haloperidol, as measured by the maximum change in the mean [SD] ESRS total score (1.40 [2.60] vs 5.61 [5.21] vs 9.04 [6.21], respectively; P <or= 0.001). The increase in BMI after 6 months was significantly greater in the RLAI group than in oral haloperidol-treated patients (mean [SD], 3.9 [1.9] vs 2.2 [1.3] kg/m(2); P = 0.001) but not significantly different from oral risperidone (3.4 [2.0] kg/m(2); P = NS). Four patients in the RLAI group had adverse events that were possibly related to prolactin, compared with 1 each in the oral risperidone and haloperidol groups. The findings of this post hoc analysis suggest that there were advantages in terms of efficacy, fewer extrapyramidal symptoms, and more weight gain with long-acting injectable second-generation antipsychotics as compared with oral antipsychotic treatment in early-episode psychosis.

Emsley R ，Oosthuizen P ，Koen L ，Niehaus DJ ，Medori R ，Rabinowitz J ... -  《CLINICAL THERAPEUTICS》

Effectiveness of risperidone long-acting injection in first-episode schizophrenia: in naturalistic setting.

Kim B ，Lee SH ，Choi TK ，Suh S ，Kim YW ，Lee E ，Yook KH ... -  《-》

The combined use of risperidone long-acting injection and clozapine in patients with schizophrenia non-adherent to clozapine: a case series.

Se Hyun Kim ，Dong Chung Jung ，Yong Min Ahn ，Yong Sik Kim ... -  《-》