Petrus Oosthuizen

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.

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.

Symptom recurrence following intermittent treatment in first-episode schizophrenia successfully treated for 2 years: a 3-year open-label clinical study

OBJECTIVE An unanswered question in the management of schizophrenia is how long antipsychotic treatment should be continued after a single psychotic episode. In this study, we assessed the rates of symptom recurrence with intermittent treatment in patients with a first episode of DSM-IV-defined schizophrenia or related illness after 2 years of successful continuous treatment. We also investigated antecedents of recurrence, as well as demographic and baseline clinical predictors of early recurrence, and we compared the psychopathology of the recurrence episode with that of the first episode. METHOD Outpatients in an academic psychiatric hospital setting (single site) who had responded well in an open-label study with risperidone long-acting injection were recruited for this intermittent treatment trial, and those who participated had their treatment tapered and discontinued over a period of up to 6 weeks, with follow-up for 3 years or until reemergence of symptoms. Open-label treatment with oral risperidone and risperidone long-acting injection was immediately reinstituted in the event of recurrence of symptoms. The study was conducted between February 2004 and March 2010. The primary outcome measure was symptom recurrence rate at 3 years. RESULTS Participants (N = 33) had a mean age ± SD of 28 ± 7.9 years and a mean baseline Positive and Negative Syndrome Scale total score ± SD of 44.8 ± 7.4 at study entry. Symptom recurrence rates were 79% at 12 months, 94% at 24 months, and 97% at 36 months. Onset of recurrence symptoms was fairly abrupt, and symptom severity returned to levels close to those of the first episode. No significant predictors of early recurrence were identified. CONCLUSIONS Intermittent antipsychotic treatment, even after 2 years of successful treatment, may not be in the best interest of patients who have experienced a single psychotic episode. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00378092.

Safety of the omega-3 fatty acid, eicosapentaenoic acid (EPA) in psychiatric patients : Results from a randomized, placebo-controlled trial

Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), are increasingly being used by psychiatric patients. Most studies have concentrated on efficacy aspects, while little is known about their safety and tolerability in psychiatric populations. This study aimed to assess the effects of EPA treatment on body mass, glucose metabolism, lipid profiles, prolactin secretion, bleeding time, haematology and liver functions. Eighty-four subjects with schizophrenia were treated with either EPA 2 g/day or placebo in addition to their antipsychotic medication for 12 weeks, in a randomized, controlled trial. Forty-seven entered a 40-week open-label extension phase of EPA 2 g/day. Seventy-four patients were included in the analysis. Six patients discontinued from the EPA group and 14 in the placebo group. Adverse event reporting was similar for the two groups. While there were no significant between-group differences, in the blinded phase the EPA group showed a significant increase in body mass index (BMI) and bleeding time. In the open-label extension, there was again a modest increase in BMI. Total cholesterol and HDL levels were significantly decreased. EPA 2 g/day is generally well tolerated. Clinicians should be aware of possible increases in bleeding time, as well as changes in weight and lipid metabolism.

Comparison of treatment response in second-episode versus first-episode schizophrenia.

Abstract This study investigated whether illness progression and treatment refractoriness emerge after relapse in schizophrenia. We compared outcomes in a cohort treated with a standardized protocol for the first and second episodes of illness. The sample comprised 31 participants who (1) had successfully completed a 2-year open-label treatment phase with risperidone long-acting injection (RLAI) for a first episode of schizophrenia; (2) underwent an intermittent treatment extension phase up to 3 years or until recurrence, and (3) entered a further 2-year treatment phase with RLAI for a recurrence episode. For the patients who remained in treatment (n = 14 [45%]), Positive and Negative Syndrome Scale score reductions, response rates, remission rates, time to response, time to remission, functional outcome scores, and modal RLAI doses were similar for the 2 treatment periods. However, 17 (55 %) of the 31 patients discontinued the study in the second episode compared with 14 (28%) of 50 patients in the first episode, suggesting reduced effectiveness of antipsychotics when reintroduced after illness recurrence. Most notably, emergent treatment nonresponsiveness was observed in 5 participants (16%), consistent with the hypothesis that relapse may be biologically harmful in a subset of patients.

Cognitive-Perceptual Deficits and Symptom Correlates in First-Episode Schizophrenia

Background Thought disorder and visual-perceptual deficits have been well documented, but their relationships with clinical symptoms and cognitive function remain unclear. Cognitive-perceptual deficits may underscore clinical symptoms in schizophrenia patients. Aim This study aimed to explore how thought disorder and form perception are related with clinical symptoms and cognitive dysfunction in first-episode schizophrenia. Setting Forty-two patients with a first-episode of schizophrenia, schizophreniform or schizoaffective disorder were recruited from community clinics and state hospitals in the Cape Town area. Methods Patients were assessed at baseline with the Rorschach Perceptual Thinking Index (PTI), the Positive and Negative Syndrome Scale (PANSS) and the MATRICS Cognitive Consensus Battery (MCCB). Spearman correlational analyses were conducted to investigate relationships between PTI scores, PANSS factor analysis-derived domain scores and MCCB composite and subscale scores. Multiple regression models explored these relationships further. Results Unexpectedly, poor form perception (X- %) was inversely correlated with the severity of PANSS positive symptoms (r = -0.42, p = 0.02). Good form perception (XA%) correlated significantly with speed of processing (r = 0.59, p < 0.01), working memory (r = 0.48, p < 0.01) and visual learning (r = 0.55, p < 0.01). PTI measures of thought disorder did not correlate significantly with PANSS symptom scores or cognitive performance. Conclusions Form perception is associated with positive symptoms and impairment in executive function during acute psychosis. These findings suggest that there may be clinical value in including sensory-perceptual processing tasks in cognitive remediation and social cognitive training programmes for schizophrenia patients.