A 1-year double-blind study of 2 doses of long-acting risperidone in stable patients with schizophrenia or schizoaffective disorder

Department of Psychiatry, Keck School of Medicine of the University of Southern California, Los Angeles, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 09/2006; 67(8):1194-203.
Source: PubMed


This study examined the effects of 2 doses of long-acting risperidone injection in patients with schizophrenia or schizoaffective disorder.
This 52-week, prospective, randomized, double-blind, multicenter, international study included clinically stable outpatients with schizophrenia or schizoaffective disorder (DSM-IV criteria). Settings included physicians' offices and clinics. Patients received a fixed dose of long-acting risperidone (25 or 50 mg) every 2 weeks. Primary outcome was time to relapse, defined as either re-hospitalization or other exacerbation criteria. Other assessments included the Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity of Illness scale, and functional and quality-of-life measures. Safety was assessed via treatment-emergent adverse events, laboratory tests, and movement disorder rating scales. Data were collected from December 2002 to September 2004.
A total of 324 patients were randomized to 25 mg (N = 163) or 50 mg (N = 161) of long-acting risperidone. Time to relapse was comparable (p = .131) for both groups. Projected median time to relapse was 161.8 weeks (95% CI = 103.0 to 254.2) with 25 mg and 259.0 weeks (95% CI = 153.6 to 436.8) with 50 mg. One-year incidences of relapse were 21.6% (N = 35) and 14.9% (N = 24), respectively (p = .059). Psychiatric hospitalization was the reason for relapse for 16 (10%) in the 25-mg group and 10 (6%) in the 50-mg group. Patients experienced statistically significant but modest improvements at endpoint in most measures (i.e., psychotic symptoms, functioning, movement disorder severity) with both doses, with no significant between-group differences.
In this 1-year study, long-acting risperidone was associated with low relapse and rehospitalization rates, indicating that doses of 25 to 50 mg are appropriate for long-term treatment in schizophrenia.

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    • "Reported components of the definition for relapse. Hospitalization [11,15-59]; Positive and Negative Syndrome Scale (PANSS) [7,15,17,18,60-72]; Clinical Global Impression (CGI) scale [17,18,26,30,52,57,60-62,65],[66,68,71,73,74]; exacerbation/re-emergence of symptoms [7,27,29,34,38,43,63,67],[75-81]; deliberate self-harm or violent behaviour, suicidal or homicidal ideation, arrest [18,23,27,43,49,50,57,65],[66,71,74,82-84]; Brief Psychiatric Rating Scale (BPRS) [28,43,71,76,84-91]; change of medication or patient management [18,27,38,41,56,66,75,92]; exacerbation/re-emergence of symptoms leading to hospitalization [20,66,92-96]; clinical assessment of patient notes [38,57,88]; International Classification of Diseases (ICD) criteria [70,89,97]; Global Assessment of Functioning (GAF) [64,72]; physician interview and/or assessment [86,98]; Present State Examination (PSE) [84]; Global Assessment Scale (GAS) [84]; Target Symptoms Ratings Scale (TSRS) [76]; Psychiatric Assessment Scale (PAS) [99]; scale for the assessment of positive symptoms [86]; social functioning [75]; Social and Occupational Functioning Assessment Scale (SOFAS) [60]. "
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    ABSTRACT: Relapse in patients with schizophrenia has devastating repercussions, including worsening symptoms, impaired functioning, cognitive deterioration and reduced quality of life. This progressive decline exacerbates the burden of illness on patients and their families. Relapse prevention is identified as a key therapeutic aim; however, the absence of widely accepted relapse definition criteria considerably hampers achieving this goal. We conducted a literature review in order to investigate the reporting of relapses and the validity of hospitalization as a proxy for relapse in patients with schizophrenia. The primary aim was to assess the range and validity of methods used to define relapse in observational or naturalistic settings. The secondary aim was to capture information on factors that predicted or influenced the risk of relapse. A structured search of the PubMed database identified articles that discussed relapse, and hospitalization as a proxy of relapse, in patients with schizophrenia. National and international guidelines were also reviewed. Of the 150 publications and guidelines identified, 87 defined relapse and 62% of these discussed hospitalization. Where hospitalization was discussed, this was as a proxy for, or a component of, relapse in the majority of cases. However, hospitalization duration and type varied and were not always well defined. Scales were used to define relapse in 53 instances; 10 different scales were used and multiple scales often appeared within the same definition. There were 95 references to factors that may drive relapse, including non-adherence to antipsychotic medication (21/95), stress/depression (11/95) and substance abuse (9/95). Twenty-five publications discussed the potential of antipsychotic therapy to reduce relapse rates---continuous antipsychotic therapy was associated with reduced frequency and duration of hospitalization. Non-pharmacological interventions, such as psychoeducation and cognitive behavioural therapy, were also commonly reported as factors that may reduce relapse. In conclusion, this review identified numerous factors used to define relapse. Hospitalization was the factor most frequently used and represents a useful proxy for relapse when reporting in a naturalistic setting. Several factors were reported to increase the risk of relapse, and observation of these may aid the identification of at-risk patients.
    Full-text · Article · Oct 2013 · Annals of General Psychiatry
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    • "However, only a minority of patients discontinued due to lack of efficacy. Discontinuation rates were similar to results from other studies in non-acute schizophrenic patients using long-acting risperidone [14-16] and the majority of patients in the poor baseline categories remained in the study. "
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    ABSTRACT: Background: This analysis of pooled data evaluates treatment outcomes of patients with schizophrenia receiving maintenance treatment with olanzapine long-acting injection (OLAI) by means of a categorical approach addressing the symptomatic and functional status of patients at different times. Methods: Patients were grouped into 5 categories at baseline, 6 months, and 12 months. Shifts between categories were assessed for individual patients and factors associated with improvement were analyzed. 1182 patients from 3 clinical trials were included in the current analysis. Results: At baseline, 434 (36.8%) patients had minimal Positive and Negative Syndrome Scale (PANSS) symptoms but seriously impaired Heinrich Carpenter's Quality of Life Scale (QLS) functioning; 303 (25.6%) had moderate to severe symptoms and seriously impaired function; 208 (17.6%) had mild to moderate symptoms but good functioning, and 162 (13.7%) had minimal symptoms and good functioning. Baseline category was significantly associated with Clinical Global Impression--Severity (CGI-S), extrapyramidal symptoms, working status, age, and number of previous episodes. The majority of all patients starting OLAI treatment maintained or improved (62% at 6 months and 52% at 12 months) their symptom and functioning levels on OLAI maintenance treatment. Less than 8% of the patients showed worsening of symptoms or functioning. An improvement in category was associated with high PANSS positive and low CGI-S scores at baseline. Conclusions: We present evidence that a composite assessment of schizophrenic patients including symptom severity and functioning is helpful in the evaluation of maintenance treatment outcomes. This approach could also be useful for the assessment of treatment options in clinical practice.The trials from which data are reported here were registered on as NCT00088491, NCT00088465, and NCT00320489.
    Full-text · Article · Aug 2012 · BMC Psychiatry
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    • "For example, a 12-week, doubleblind , placebo-controlled randomized study of 400 patients with schizophrenia receiving either 25-, 50-or 75 mg biweekly intramuscular injections of placebo or long-acting risperidone found significant improvement on the positive and negative syndrome scale (PANSS) scores for long-acting risperidone relative to placebo (Kane et al., 2003). In another randomized, double-blind 52-week study with risperidone long-acting injectable 25 mg or 50 mg every 2 weeks (N=324), risperidone long-acting injectable 50 mg had a lower rate of relapse and also significant improvements in psychosocial functioning (Simpson et al., 2006). "
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    ABSTRACT: OBJECTIVE: Treatment of schizophrenia in patients with comorbid substance use (alcohol/illicit drug use, abuse or dependence) presents challenges for public health systems. Substance use in people with schizophrenia is up to four times greater than the general population and is associated with medication nonadherence and poor outcomes. Therefore, continuous antipsychotic treatment in this population may pose more of a challenge than for those with schizophrenia alone. Many clinical trials and treatment recommendations in schizophrenia do not take into consideration substance use as people with comorbid substance use have typically been excluded from most antipsychotic trials. Nonetheless, antipsychotic treatment appears to be as efficacious in this population, although treatment discontinuation remains high. The objective of this review was to highlight the importance and utility of considering long-acting injectable antipsychotics for patients with schizophrenia and comorbid substance use. METHODS: We did a literature search using PubMed with key words schizophrenia and substance use/abuse/dependence, nonadherence, antipsychotics, long acting injectables, relapse, and psychosocial interventions. We limited our search to human studies published in English and 4,971 articles were identified. We focused on clinical trials, case reports, case series, reviews and meta-analyses resulting in 125 articles from 1975-2011. RESULTS: Our review suggests the potential role of long-acting injectables for people with comorbid substance use and schizophrenia in leading to improvements in psychopathology, relapse prevention, fewer rehospitalizations, and better outcomes. CONCLUSIONS: While more research is needed, long-acting antipsychotics should be considered an important option in the management of people with schizophrenia and comorbid substance use.
    Full-text · Article · Jul 2012 · Journal of Dual Diagnosis
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