Liezl Koen

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.

Duration of untreated psychosis and outcome in first-episode psychosis. Perspective from a developing country

Objective:  To investigate the association between duration of untreated psychosis (DUP) and treatment outcome in a sample of subjects from a developing country.

The effects of eicosapentaenoic acid in tardive dyskinesia: A randomized, placebo-controlled trial

OBJECTIVE Worldwide, conventional antipsychotic medication continues to be used extensively, and tardive dyskinesia (TD) remains a serious complication. The primary objective of the present study was to compare the efficacy of EPA versus placebo in reducing symptoms of TD. METHOD This was a 12-week, double-blinded, randomized study of ethyl-EPA 2g/day versus placebo as supplemental medication, in patients with schizophrenia or schizoaffective disorder, with established TD. RESULTS Eighty-four subjects were randomized, of whom 77 were included in the analysis. Both the EPA and placebo groups displayed significant baseline to endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores, but there were no significant between-group differences (p=0.4). Response rates (>or=30% improvement in TD symptoms) also did not differ significantly between EPA-treated subjects (45%) and placebo-treated subjects (32%) (p=0.6). However, a post-hoc linear mixed model repeated measures analysis of variance indicated an effect for treatment group and duration of TD. The EPA-treated patients had significantly greater mean reductions in dyskinesia scores initially, although this was not sustained beyond 6 weeks. CONCLUSIONS This trial failed to demonstrate an anti-dyskinetic effect for ethyl-EPA 2g/day on the primary efficacy measure. However, a modest and transient benefit is suggested in patients with more recent onset of TD. The lack of clear-cut efficacy could be explained on the basis of the dose of EPA being too low, the study being underpowered, TD being too chronic in the majority of cases, differences in dietary fatty acid intake, or that EPA lacks an anti-dyskinetic action.

Perceptions of a South African schizophrenia population with regards to community attitudes towards their illness

BackgroundWith the worldwide shift towards a more community-based psychiatric service delivery approach, stigma and the issues surrounding it have received much attention. However, very little South African data exist and the aim of our study was therefore to investigate the experience of internalized stigma in a South African schizophrenia population with specific emphasis on abuse as a form of stigmatization.MethodsA total of 100 subjects at various stages of schizophrenic illness were subjected to a the Internalized Stigma of Mental Illness scale (ISMI) that was modified to include six items focusing specifically on investigating the experience of stigmatization within the South African context.ResultsA high overall degree of stigmatization was perceived by most subjects, but not equally so for all ISMI areas. When looking at the modified items, 29% felt media-influence to be negative, this seemed to be specifically true for those with matriculation and higher as well as a home-language other than Afrikaans. Thirty nine percent indicated that they had been victims of physical abuse due to their mental illness, with the data suggesting that especially Xhosa-speaking patients, male subjects and those with more admissions and a longer duration of illness experienced this excessively.DiscussionOur study confirmed a high overall degree of perceived stigmatization as well as suggesting some evidence for cultural influences on stigma. It was the first to provide South African data and as such can be regarded as central to our efforts in restructuring psychiatric services and clinical practices in a way that would minimize the effects of stigma and ultimately benefit our clients.

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.

Deficits in facial affect recognition in unaffected siblings of Xhosa schizophrenia patients: evidence for a neurocognitive endophenotype.

The present study in an African Xhosa sample examined whether familial vulnerability to schizophrenia is associated with deficits in facial affect recognition. Healthy comparison subjects, unaffected siblings of schizophrenia patients, and schizophrenia patients were tested with a task requiring rapid recognition of matched positive (happy), negative (angry), and neutral facial expressions. Siblings and patients demonstrated impaired recognition of negative relative to positive facial expressions whereas comparison subjects recognized negative and positive expressions at an equal level of accuracy. These results suggest that deficits in the processing negative affect from social cues are transmitted in families and may represent a heritable endophenotype of schizophrenia.

Elucidation of CYP2D6 genetic diversity in a unique African population: implications for the future application of pharmacogenetics in the Xhosa population.

Genetic variation of the CYP2D6 gene has been associated with altered drug metabolism; however, limited studies have investigated CYP2D6 sequence diversity in African populations. We devised a CYP2D6 genotyping strategy to analyse the South African Xhosa population and genotype a Xhosa schizophrenia cohort, as CYP2D6 metabolises many antipsychotics and antidepressants.

Characterization of the genetic profile of CYP2C19 in two South African populations

AIMS This study was aimed at elucidating the common sequence variation present in the CYP2C19 gene within the South African Xhosa population and comparing it with the Cape Mixed Ancestry (CMA) population for possible future pharmacogenetic applications. MATERIALS & METHODS Common sequence variation was identified through the resequencing of 15 Xhosa individuals. The detected variants were prioritized for genotyping in an additional 85 Xhosa and 75 CMA individuals, while 5 -upstream variants were analyzed using dual luciferase reporter assays. RESULTS Resequencing of the Xhosa population revealed 30 variants, including the novel CYP2C19*27 and CYP2C19*28 alleles. CYP2C19*27, characterized by -1041G>A, caused a twofold decrease in luciferase activity, while CYP2C19*28 is characterized by the nonsynonymous V374I variant. In addition, the previously characterized variants, CYP2C19*2, CYP2C19*9 and CYP2C19*17, were present in both populations, while CYP2C19*3 was only observed in the CMA population. CONCLUSION Our data demonstrate that both the Xhosa and CMA populations exhibit unique genetic profiles that could influence the outcome of drug therapy in these populations.

Association between the MnSOD Ala-9Val polymorphism and development of schizophrenia and abnormal involuntary movements in the Xhosa population.

Reactive oxygen species (ROS)-mediated damage has been hypothesized to play a role in the development and poor outcome of schizophrenia, as well as the development of neuroleptic-induced abnormal involuntary movements. Recently, the functional polymorphism (Ala-9Val) in the manganese superoxide dismutase (MnSOD) gene (part of the antioxidant defense mechanism) was found to be associated with schizophrenia in a Turkish population. This study was aimed at replicating this finding in a Xhosa population. In addition, the role of Ala-9Val in abnormal involuntary movement and tardive dyskinesia development in the Xhosa population was also investigated. The schizophrenic patient group (n=286) and a healthy control group (n=243) were genotyped for the Ala-9Val polymorphism using heteroduplex-single stranded conformational polymorphism (HEX-SSCP) analysis. No significant difference in genotype or allele frequency could be observed between the schizophrenia and control group (P=0.294 and P=0.528 respectively). In addition no association could be found between the polymorphism and symptom severity (SANS and SAPS). The Xhosa schizophrenia patient group with abnormal involuntary movements (n=54) and a subgroup with tardive dyskinesia (n=30) was found to significantly differ in Ala-9Val genotype frequency (P=0.008 and P=0.011 respectively) compared to the Xhosa schizophrenia patient group without abnormal involuntary movements (n=204). However, no significant difference was found for the allele frequencies (P=0.955 and P=0.161). Further, using ANCOVA no association was found between AIMS score and genotype in the group with abnormal involuntary movements (P=0.1234). However, in the patient group with tardive dyskinesia an association was observed between genotype and AIMS score (P=0.0365). These results do not support a major role of the MnSOD Ala-9Val polymorphism in the development of schizophrenia or symptom severity in the Xhosa population. Yet it seems to be involved in the development of abnormal involuntary movements and tardive dyskinesia and may even modulate the severity of tardive dyskinesia.