Lebogang Phahladira

A randomized, controlled trial of omega-3 fatty acids plus an antioxidant for relapse prevention after antipsychotic discontinuation in first-episode schizophrenia.

BACKGROUND While antipsychotics are effective in the maintenance treatment of schizophrenia they have safety and tolerability risks. We investigated whether a combination of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and a metabolic antioxidant, alpha-lipoic acid (α-LA), is effective in preventing relapse after antipsychotic discontinuation in subjects who were successfully treated for 2-3 years after a first-episode of schizophrenia, schizo-affective or schizophreniform disorder. METHODS In this randomized, double-blind, placebo controlled study antipsychotic treatment was tapered and discontinued and participants received either ω-3 PUFAs (eicosapentaenoic acid 2g/day and docosahexaenoic acid 1g/day)+α-LA 300 mg/day or placebo. Subjects were followed up for two years, or until relapse. RESULTS Recruitment was terminated prematurely due to the high relapse rates in both treatment groups as well as the severity of some of the relapse episodes. Of the 33 participants, 19/21(90%) randomized to ω-3 PUFAs+α-LA relapsed and one (5%) completed two years without relapse (p=0.6); and 9/12 (75%) randomized to placebo relapsed and none completed two years without relapse. Mean times to relapse were 39.8 ± 25.4 and 38.3 ± 26.6 weeks for the ω-3 PUFAs+α-LA and placebo groups, respectively (p=0.9). There were no significant differences between the groups in relapse symptom severity. CONCLUSIONS We found no evidence that ω-3 PUFAs+α-LA could be a suitable alternative to maintenance antipsychotic treatment in relapse prevention, in this small study. Antipsychotic discontinuation after a single episode of schizophrenia carries a very high risk of relapse, and treatment guidelines endorsing this practice should be revised.

Rate and predictors of non-response to first-line antipsychotic treatment in first-episode schizophrenia†

The goals of this study were to (i) estimate the rate of non‐response to first‐line treatment in first‐episode schizophrenia, (ii) evaluate other outcomes associated with symptom non‐response and (iii) identify demographic, baseline clinical and early treatment response predictors of non‐response.

Brain volume changes over the first year of treatment in schizophrenia: relationships to antipsychotic treatment

BACKGROUND Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported. METHODS We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain). RESULTS Excessive cortical volume reductions were observed in patients [-4.6 (6.6)%] v. controls [-1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis. CONCLUSIONS Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.

How long should antipsychotic treatment be continued after a single episode of schizophrenia

Purpose of review In this article, recent publications addressing the pros and cons of antipsychotic maintenance treatment are reviewed and some recommendations formulated. Recent findings On one hand, relapse rates are extremely high when antipsychotic treatment is discontinued, even after a single episode of psychosis; there are no reliable predictors of relapse; and there are serious psychosocial and biological consequences of relapse. On the other hand, in addition to the well recognised side-effect burden of antipsychotics, a few recent publications suggest an association between greater exposure to antipsychotic treatment and poorer long-term outcome. Summary There is more evidence in favour of maintaining patients on antipsychotics than on stopping them. There is an urgent need for more and better research before the question of duration of maintenance after a single episode of schizophrenia can be answered with confidence. Until such studies have been conducted, clinicians should prioritize relapse prevention, particularly in the early years of illness, by encouraging indefinite, continuous antipsychotic treatment, and avoid unnecessary side-effects by using the lowest possible effective dose and selecting the best tolerated antipsychotic.

Neurological soft signs in first-episode schizophrenia: State- and trait-related relationships to psychopathology, cognition and antipsychotic medication effects

BACKGROUND Neurological soft signs (NSS) are proposed to represent both state- and trait-related features of schizophrenia. METHOD We assessed the course of NSS with the Neurological Evaluation Scale (NES) over 12months of standardised treatment in 126 patients with first-episode schizophrenia, schizophreniform or schizoaffective disorder, and evaluated their state- and trait-related associations with psychopathology, functionality, cognition and antipsychotic treatment. We considered change scores from baseline to be state-related and endpoint scores to be trait-related. RESULTS Significant effects for time were recorded for all NSS domains. For state-related change-scores greater improvements in sensory integration were predicted by more improvement in working memory (p=0.01); greater improvements in motor sequencing scores were predicted by more improvement in working memory (p=0.005) and functionality (p=0.005); and greater improvements in NES Total score were predicted by more improvement in disorganised symptoms (p=0.02). There were more substantial associations between trait-related endpoint scores than for state-related change scores. For endpoint scores lower composite cognitive score predicted poorer sensory integration (p=0.001); higher Parkinsonism score predicted poorer motor co-ordination (p=0.0001); lower composite cognitive score (p=0.001) and higher Parkinsonism score (p=0.005) predicted poorer motor sequencing; higher Parkinsonism score (p=0.0001) and disorganised symptoms (p=0.04), and lower composite cognitive score (p=0.0007) predicted higher NES total score. CONCLUSIONS NSS improved with treatment, but were weakly associated with improvements in psychopathology. Studies investigating NSS as trait-markers should ensure that patients have been optimally treated at the time of testing, and should take possible effects of extrapyramidal symptoms into account.

Instruments measuring blunted affect in schizophrenia : a systematic review

Blunted affect, also referred to as emotional blunting, is a prominent symptom of schizophrenia. Patients with blunted affect have difficulty in expressing their emotions. The work of Abrams and Taylor and their development of the Rating Scale for Emotional Blunting in the late 1970’s was an early indicator that blunted affect could indeed be assessed reliably. Since then, several new instruments assessing negative symptoms with subscales measuring blunted affect have been developed. In light of this, we aim to provide researchers and clinicians with a systematic review of the different instruments used to assess blunted affect by providing a comparison of the type, characteristics, administration and psychometric properties of these instruments. Studies reporting on the psychometric properties of instruments assessing blunted affect in patients with schizophrenia were included. Reviews and case studies were excluded. We reviewed 30 full-text articles and included 15 articles and 10 instruments in this systematic review. On average the instruments take 15–30 minutes to administer. We found that blunted affect items common across all instruments assess: gestures, facial expressions and vocal expressions. The CAINS Self-report Expression Subscale, had a low internal consistency score. This suggests that this sub-scale does not reliably assess patients’ self-reported blunted affect symptoms and is likely due to the nature of blunted affect. Instruments correlated minimally with instruments measuring positive symptoms and more importantly with depression suggesting that the instruments distinguish between seemingly similar symptoms.

Effects of cannabis use on body mass, fasting glucose and lipids during the first 12 months of treatment in schizophrenia spectrum disorders

While acute cannabis use stimulates appetite, general population studies suggest that chronic use is associated with reduced risk of obesity and other cardiometabolic risk factors. In this study we investigated changes in body mass index (BMI), fasting blood glucose and lipids, and rates of metabolic syndrome risk factors in cannabis users vs. non-users in 109 minimally treated patients with first-episode schizophrenia, schizophreniform or schizo-affective disorder who were treated according to a standardized treatment regime with depot antipsychotic medication over 12 months. Participants underwent repeated urine toxicology tests for cannabis and those testing positive at any time during the study (n = 40), were compared with those who tested negative at all time points (n = 69). There was a significant group*time interaction effect (p = 0.002) with the cannabis negative group showing a greater increase in BMI than the cannabis positive group, after adjusting for age, sex, methamphetamine use and modal dose of antipsychotic. There were no group*time interaction effects for fasting blood glucose or lipids. Post hoc tests indicated significant increases in fasting blood glucose and triglycerides and a decrease in high-density lipoprotein cholesterol for the cannabis negative group, with no significant changes in the cannabis positive group. Rates of metabolic syndrome did not differ significantly between groups, although more cannabis negative patients had elevated waist-circumference at endpoint (p = 0.003). It may be that chronic cannabis use directly suppresses appetite, thereby preventing weight gain in users. However, other indirect effects such as dietary neglect and smoking may be contributory and could explain our findings.

F106. STATE AND TRAIT RELATED NATURE OF INSIGHT IMPAIRMENT IN SCHIZOPHRENIA

Abstract Background Impairment of insight is a prominent feature of schizophrenia and is associated with poor adherence and poor outcomes. While many studies have investigated the nature of insight impairment in schizophrenia, few have charted its course longitudinally. In this study we investigated changes in different components of insight during the first 12 months of antipsychotic treatment. Methods The sample comprised 107 never or minimally treated patients with a first episode of schizophrenia, schizophreiform or schizoaffective disorder. They were treated according to a fixed protocol with flupenthixol decanoate. Insight was assessed with the self-rating Birchwood Insight Scale and the investigator rated global insight item of the PANSS scale.Psychopathology was assessed with the PANSS and CDSS. Cognitive performance was assessed with the MATRICS. We performed evaluations at baseline, month 6 and month 12. Linear mixed effects mixed models for repeated measures were conducted to assess changes over time, adjusting for age, gender and educational status. Results There were no significant changes in the BIS subscales of symptom awareness, awareness of illness or total BIS score. The need for treatment subscale improved slightly (p=0.02) while the PANSS global insight improved considerably (p<0.0001). Degree of insight impairment was only weakly correlated with psychopathology and cognition Discussion Insight impairment is common in schizophrenia and displays trait-like rather than state-like features. These findings have important clinical implications.

S100. EFFECTS OF CANNABIS USE ON BODY MASS, FASTING GLUCOSE AND LIPIDS DURING THE FIRST 12 MONTHS OF TREATMENT IN SCHIZOPHRENIA SPECTRUM DISORDERS

Abstract Background Acute cannabis use stimulates appetite, while general population studies suggest that chronic use is associated with reduced risk of obesity and other cardiometabolic risk factors. Methods In this study, we investigated changes in body mass index (BMI), fasting blood glucose and lipids, and rates of metabolic syndrome risk factors in cannabis users vs. non-users in 109 minimally treated patients with first-episode schizophrenia, schizophreniform or schizo-affective disorder who were treated according to a standardized treatment regime with depot antipsychotic medication over 12 months. Participants underwent repeated urine toxicology tests for cannabis and those testing positive at any time during the study (n=40), were compared with those who tested negative at all time points (n=69). Results There was a significant group*time interaction effect (p=0.002) with the cannabis negative group showing a greater increase in BMI than the cannabis positive group, after adjusting for age, sex, methamphetamine use and modal dose of antipsychotic. There were no group*time interaction effects for fasting blood glucose or lipids. Post hoc tests indicated significant increases in fasting blood glucose and triglycerides and a decrease in high-density lipoprotein cholesterol for the cannabis negative group, with no significant changes in the cannabis positive group. Rates of metabolic syndrome did not differ significantly between groups. However, more cannabis negative patients had elevated waist-circumference at endpoint (p=0.003). Discussion Although other indirect effects such as dietary neglect and smoking may be contributory and could explain our findings, it may be that chronic cannabis use directly suppresses appetite, thereby preventing weight gain in users.