Background: 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. Objective: 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. Methods: 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; ≤2 hospitalizations for psychosis; and lifetime exposure to ≤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). Results: 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/m2). 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/m2). 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 ≤ 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/m2; P = 0.001) but not significantly different from oral risperidone (3.4 [2.0] kg/m2; 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. Conclusions: 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.
Bibliographical noteFunding Information:
This study was funded by Janssen-Cilag. Dr. Emsley has participated in speakers' and advisory boards and received honoraria from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Janssen-Cilag, Lundbeck, Organon Pharmaceuticals, Pfizer, Servier, and Wyeth Pharmaceuticals. He has received research funding from Janssen-Cilag, Lundbeck, and AstraZeneca Pharmaceuticals. Dr. Oosthuizen has participated in speakers' and advisory boards and received honoraria from AstraZeneca Pharmaceuticals, Eli Lilly, Janssen-Cilag, and Pfizer. Dr. Rabinowitz has received research support and/or consultancy fees and/or travel support from Janssen-Cilag, Janssen Pharmaceuticals, Eli Lilly, Pfizer, Bioline, Newron Pharmaceutical, and Novartis Pharmaceuticals, and was a paid consultant on this study. Drs. Koen and Niehaus have no financial interests to declare.