Rossella Medori

Efficacy and safety of direct transition to risperidone long-acting injectable in patients treated with various antipsychotic therapies

The maintained antipsychotic efficacy of risperidone long-acting injectable (RLAI) was investigated in patients with schizophrenia or other psychoses who were transitioned directly from their previous antipsychotic medication. Patients symptomatically stable, but considered to require a treatment change, received 25 mg of RLAI (increased to 37.5 or 50 mg, if necessary) every 2 weeks for 6 months. Assessments included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression–Severity (CGI-S), Global Assessment of Functioning (GAF), SF-36 Health-Related Quality of Life Questionnaire and Extrapyramidal Symptoms Rating Scale (ESRS). Of 1876 patients enrolled, 74% completed the 6-month study. The most frequent reasons for treatment change were non-compliance (38%), insufficient efficacy (33%) and side-effects (26%). There was a significant reduction from baseline to endpoint in mean total PANSS score and in the scores on all PANSS subscales and symptom factors (P<0.001). CGI-S improved significantly, as did mean GAF score, all factors on the SF-36 and patient satisfaction with treatment. Scores on ESRS showed significant, sustained improvements throughout the study period. Direct initiation of RLAI was effective and well tolerated. RLAI provides an advancement in the treatment options available for a wide range of patients requiring long-term antipsychotic therapy.

Long-acting injectable risperidone in the treatment of subjects with recent-onset psychosis: a preliminary study.

Using a long-acting antipsychotic to improve adherence early in the illness may reduce relapse rates and promote sustained remission, thereby improving the long-term outcome of schizophrenia. We assessed whether risperidone long-acting injection (RLAI) could be used safely and effectively in the treatment of recent-onset psychosis. Fifty patients aged 15 to 43 years with newly diagnosed schizophreniform disorder or schizophrenia were treated with RLAI 25 to 50 mg every 2 weeks for 2 years. Thirty-six patients (72%) completed the trial. Of 39 (78%) who showed a clinical response of 50%, 4 relapsed. Thirty-two patients (64%) achieved remission. Mean maximum increase in Extrapyramidal Symptoms Rating Scale total score was 1.4 (95% confidence interval, 0.61-2.10; n = 50); 10 patients required anticholinergic medication, and 1 subject developed persistent dyskinesia. Prolactin levels were elevated in 18 patients, 4 of whom reported possible prolactin-related adverse events. Mean increase in body mass index to last visit for all patients was 4.8 kg/m2 (SD, 3.8 kg/m2). The final RLAI dose was 25 mg for 54% of patients, 37.5 mg for 30%, and 50 mg for 16%. This preliminary study suggests that RLAI was overall well tolerated and appears to be effective in recent-onset psychosis. Further investigation is warranted.

Remission in patients with first-episode schizophrenia receiving assured antipsychotic medication: A study with risperidone long-acting injection

Recently proposed criteria for remission by a ‘Remission in Schizophrenia Working Group’ have generated considerable interest. We assessed rates, predictors, and correlates of remission in a sample of patients with first-episode schizophrenia treated with injectable, long-acting risperidone. This allowed us to examine remission among patients known to be receiving medication. This was a single-site open-label study in which 50 newly diagnosed cases of schizophreniform disorder or schizophrenia aged 16 to 43 years were treated with injectable, long-acting risperidone 25–50 mg every 2 weeks for 2 years. Remission, according to Remission in Schizophrenia Working Group criteria, was achieved in 64% of the patients. Of those achieving remission, 97% maintained this status until study completion. Remission was associated with greater improvements in other symptom domains, insight, and social and occupational functioning. Patients in remission received lower doses of antipsychotic medication, had fewer extrapyramidal symptoms, and a more favorable attitude toward medication. The results of this open-label study suggest that a majority of first-episode patients who receive long-acting injectable antipsychotic medication may achieve sustained remission. Double-blind-controlled studies using long-acting injectable antipsychotics in early psychosis are warranted to further test this.

Direct transition to long-acting risperidone : analysis of long-term efficacy

This report presents data from the extension phase of a 6-month trial that evaluated the efficacy of risperidone long-acting injectable (RLAI) in stable psychotic patients requiring a treatment change. Patients continued to receive RLAI every 2 weeks for a maximum of 12 months from study entry. Symptoms were assessed using the PANSS after 1, 3, 6, 9 and 12 months of treatment (or treatment endpoint). Remission of severity criteria were defined as ≤3 points in all PANSS items suggested by the Remission in Schizophrenia Working Group. 715 patients (63% male) entered the extension phase and 508 completed the 12-month study. The mean PANSS total score at Day 0 was 74.9±22.7. This was significantly reduced after 1 month (67.7 ±22.3, p≤0.001), with continued improvements over the 12 months of the study until treatment endpoint (59.7±21.9). Significant improvements from Day 0 to endpoint were also seen in the scores for all PANSS subscales and symptom factors. The proportion of patients who met the PANSS severity criteria for remission increased from 29% at Day 0 to 60% at endpoint, and the proportion of patients who met these criteria for ≤ 6 months increased from 24% at Month 6 to 45% at endpoint. Treatment with RLAI for up to 12 months provided significant and sustained improvements in symptom control in patients with schizophrenia. These improvements may help patients to achieve and remain in remission.

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

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; <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). 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/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. 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.

Patients in the early phases of schizophrenia and schizoaffective disorders effectively treated with risperidone long-acting injectable.

The efficacy and safety of risperidone long-acting injectable (RLAI) was investigated in patients in the early phases of schizophrenia and schizoaffective disorders (≤ 3 years). Patients who required a treatment change received RLAI (2-weekly gluteal injections of 25, 37.5 or 50mg, per clinical judgement), without an oral risperidone run-in phase. A total of 382 patients were included in this 6-month open-label study; 73% of patients completed the study. A total of 84% had schizophrenia with a median duration of 1.0 year since diagnosis. Previous medications were mainly atypical antipsychotics (70%) and depot neuroleptics (24%). The main reasons for treatment change were non-compliance (42%) and insufficient efficacy (31%) of previous medication. The total Positive and Negative Syndrome Scale (PANSS) and all its subscale scores improved significantly (p ≤ 0.0001), with 40% of patients showing a 20% improvement on total PANSS. Global Assessment of Functioning, quality of life, patient satisfaction and movement disorders also improved significantly. Tolerability of RLAI was generally good and no unexpected adverse events were reported. The ensured delivery of medication with RLAI resulted in significant symptom improvement in this patient population. Direct initiation of RLAI is well accepted by patients. RLAI might represent a novel option for patients in the early phases of psychosis.

12-month efficacy and safety of OROS MPH in children and adolescents with attention-deficit/hyperactivity disorder switched from MPH.

PurposeThe aim of this study was to evaluate long-term clinical treatment with OROS® methylphenidate (MPH) (Concerta®) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) who had been previously treated with immediate release (IR) MPH.MethodsSubjects aged 6–16 years (n=105) who were stable on IR MPH (10–60 mg/day) were switched to 18, 36 or 54mg OROS® MPH once daily for 21 days, depending on prestudy MPH dose. Subjects who benefited from OROS® MPH could continue in a 12-month extension period. ADHD symptoms and treatment response were assessed by parents/caregivers and investigators.ResultsOut of 105 enrolled children, 101 completed the 21-day treatment phase. In all, 89 parents/caregivers (88.1%) wanted their child to continue with the study treatment into the extension phase, and 56 children (63 %) completed the 1-year trial. The parent/caregiver global assessment of satisfaction ranged from 49 to 69% during the extension phase, and 49 to 71% of investigators rated the treatment as adequate. Efficacy and satisfaction were found more commonly in patients in the older age group (10–16 years), those on a higher dose (36 mg or 54 mg) and with the predominantly inattentive ADHD subtype. OROS® MPH was well tolerated.ConclusionsChildren and adolescents can effectively and safely be switched from IR MPH to OROS® MPH with improved symptom control and compliance.

Sustained improvement of clinical outcome with risperidone long-acting injectable in psychotic patients previously treated with olanzapine

The efficacy and tolerability of risperidone long-acting injectable were investigated in patients with schizophrenia or other psychotic disorders who had previously been symptomatically stable on olanzapine treatment. Patients received risperidone long-acting injectable, 25mg, by intramuscular injection every 2 weeks; the dose could be increased to 37.5 or 50 mg if necessary. Patients were transferred directly from their previous medication to risperidone long-acting injectable without a runin period of oral risperidone treatment. Of 192 patients recruited, 134 patients (70%) completed the study. The principal reasons for discontinuation were withdrawal of consent (8%), adverse events (6%), insufficient response (5%) and non-compliance (4%). Risperidone long-acting injectable produced a significant improvement (p = 0.0001) in Positive and Negative Syndrome Scale (PANSS) total scores, from 74.2±21.3 at baseline to 65.8±21.4 at endpoint. There were also significant reductions in PANSS subscales (positive symptoms, negative symptoms, general psycho-pharmacology) and Marder factor scores. The Clinical Global Impression increased significantly from baseline to endpoint (p = 0.0001), as reflected by the increase in the proportion of patients rated as ‘not ill’ or ‘borderline ill’ from 10% at baseline to 21% at endpoint. Risperidone long-acting injectable was also associated with significant improvements in Global Assessment of Function, patient satisfaction with treatment, and quality of life, measured on the SF-36 scale. Movement disorders, measured on the Extrapyramidal Symptom Rating Scale, were significantly reduced following the change to risperidone long-acting injectable. Treatment with risperidone long-acting injectable was well tolerated, and no significant weight gain occurred during the study. This open study suggests that risperidone long-acting injectable produces symptomatic improvement in schizophrenia patients previously considered symptomatically stable with olanzapine, along with improvement in movement disorders. The combination of improved efficacy and good tolerability may have important implications for patient adherence to therapy and subsequent long-term outcomes.

Symptom control in children and adolescents with attention-deficit/hyperactivity disorder on switching from immediate-release MPH to OROS MPH Results of a 3-week open-label study.

AimThe aim of this study was to assess the impact of switching from immediate-release (IR) methylphenidate (MPH) to OROS® MPH (CONCERTA®), a once-daily long-acting MPH formulation, in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).MethodsSubjects with ADHD aged 6–16 (n=105),who were stably maintained on their current IR MPH regimen (10–60 mg/day), were switched to 18, 36 or 54mg OROS® MPH once daily for 21 days, depending on pre-study daily MPH dose.ADHD symptoms were assessed by parents, teachers and investigators.ResultsBy Day 21, parent/caregiver IOWA Conners ratings had decreased from baseline by 2.7 points to 5.2 (I/O), and by 1.8 points to 5.0 (O/D). Teacher IOWA Conners ratings were maintained. Decreases in IOWA Conners ratings are indicative of ADHD symptom improvement. Approximately 75% of parents and investigators rated therapy as good or excellent. OROS® MPH therapy was well tolerated.ConclusionsSwitching from IR MPH to OROS® MPH maintained and may have improved symptom control in children and adolescents with ADHD, during the course of this study. The changes in parent/caregiver IOWA Conners ratings suggest that OROS® MPH improves symptom control in the after-school period. This is consistent with the 12-h duration of action previously demonstrated for OROS® MPH.

Plasma antipsychotic concentration and receptor occupancy, with special focus on risperidone long-acting injectable

Although effective plasma concentration ranges have been established for some antipsychotics, conventional and atypical, there is considerable inter-patient pharmacokinetic variation. Positron-emission tomography (PET) can be used to estimate D(2)-like receptor occupancy in the brain needed for an antipsychotic effect and the level above which extrapyramidal side effects (EPS) develop. For conventional antipsychotics, the window occupancy is approximately 70-80%. For the atypical antipsychotic risperidone, the antipsychotic effect starts at approximately 60% occupancy, with occupancy above 80% leading to EPS. The new formulation, risperidone long-acting injectable (RLAI), comprises risperidone in a biodegradable polymer. It is effective long-term at doses of 25 or 50 mg injected i.m. every 2 weeks. The constant and slow release of the long-acting formulation leads to less fluctuation in plasma levels and to a D(2)-like receptor occupancy which is below the threshold for EPS.