Laila Asmal

The nature of relapse in schizophrenia

BackgroundMultiple relapses characterise the course of illness in most patients with schizophrenia, yet the nature of these episodes has not been extensively researched and clinicians may not always be aware of important implications.MethodsWe critically review selected literature regarding the nature and underlying neurobiology of relapse.ResultsRelapse rates are very high when treatment is discontinued, even after a single psychotic episode; a longer treatment period prior to discontinuation does not reduce the risk of relapse; many patients relapse soon after treatment reduction and discontinuation; transition from remission to relapse may be abrupt and with few or no early warning signs; once illness recurrence occurs symptoms rapidly return to levels similar to the initial psychotic episode; while most patients respond promptly to re-introduction of antipsychotic treatment after relapse, the response time is variable and notably, treatment failure appears to emerge in about 1 in 6 patients. These observations are consistent with contemporary thinking on the dopamine hypothesis, including the aberrant salience hypothesis.ConclusionsGiven the difficulties in identifying those at risk of relapse, the ineffectiveness of rescue medications in preventing full-blown psychotic recurrence and the potentially serious consequences, adherence and other factors predisposing to relapse should be a major focus of attention in managing schizophrenia. The place of antipsychotic treatment discontinuation in clinical practice and in placebo-controlled clinical trials needs to be carefully reconsidered.

The concepts of remission and recovery in schizophrenia.

Purpose of review Until recently outcome studies in schizophrenia lacked standardized measures, and outcome expectations were generally pessimistic. The Remission in Schizophrenia Working Group (RSWG) published operationalized criteria for symptomatic remission in 2005. These criteria have been extensively applied in research settings and have stimulated research into other components of outcome, particularly functional outcome and quality of life. Attention has also shifted beyond remission to the more difficult to attain and complex concept of recovery. The purpose of this review is to examine recent studies on these topics and to assess whether progress has been made towards a broader definition of remission and recovery. Recent findings Reported remission rates vary widely across studies (17–88%). Patients in remission do better than their nonremitted counterparts in several other outcome domains. Predictors of remission include early treatment response, and baseline symptom severity and subjective well being. Patients move in and out of remission over time. At present, there is no consensus on methods of measuring other outcome domains, particularly functional status and quality of life. Summary The RSWG remission criteria are easy to apply and define an achievable and desirable treatment goal. Measures of social and occupational functional outcome, quality of life and cognitive status need to be further developed and standardized before remission and recovery criteria can be more broadly defined.

The evidence for illness progression after relapse in schizophrenia

It has long been suspected that relapse in schizophrenia is associated with disease progression in so far as time to response is longer, negative and other symptoms persist, some patients become treatment refractory and neuroprogression in terms of structural brain changes may occur. This article examines the evidence for illness progression after relapse in patients with schizophrenia. It reports on indirect evidence obtained from retrospective, naturalistic and brain-imaging studies, as well as a few prospective studies examining pre- and post-relapse treatment response. Findings suggest that the treatment response after relapse is variable, with many patients responding rapidly, others exhibiting protracted impairment of response and a subgroup displaying emergent refractoriness. This subgroup comprises about 1 in 6 patients, irrespective of whether it is the first or a subsequent relapse, and even when the delay between onset of first symptoms of relapse and initiation of treatment is brief. While there is a lack of well-designed studies investigating the post-relapse treatment outcome, available evidence gives sufficient cause for concern that, in addition to the considerable psychosocial risks, an additional risk of biological harm may be associated with relapse.

Long-acting injectable antipsychotics in early psychosis: a literature review

There are sound reasons for considering the use of long‐acting injectable antipsychotics early in the course of schizophrenia. We reviewed available literature on the subject.

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.

A systematic review of genetic variants associated with metabolic syndrome in patients with schizophrenia

Metabolic syndrome (MetS) is a cluster of factors that increases the risk of cardiovascular disease (CVD), one of the leading causes of mortality in patients with schizophrenia. Incidence rates of MetS are significantly higher in patients with schizophrenia compared to the general population. Several factors contribute to this high comorbidity. This systematic review focuses on genetic factors and interrogates data from association studies of genes implicated in the development of MetS in patients with schizophrenia. We aimed to identify variants that potentially contribute to the high comorbidity between these disorders. PubMed, Web of Science and Scopus databases were accessed and a systematic review of published studies was conducted. Several genes showed strong evidence for an association with MetS in patients with schizophrenia, including the fat mass and obesity associated gene (FTO), leptin and leptin receptor genes (LEP, LEPR), methylenetetrahydrofolate reductase (MTHFR) gene and the serotonin receptor 2C gene (HTR2C). Genetic association studies in complex disorders are convoluted by the multifactorial nature of these disorders, further complicating investigations of comorbidity. Recommendations for future studies include assessment of larger samples, inclusion of healthy controls, longitudinal rather than cross-sectional study designs, detailed capturing of data on confounding variables for both disorders and verification of significant findings in other populations. In future, big genomic datasets may allow for the calculation of polygenic risk scores in risk prediction of MetS in patients with schizophrenia. This could ultimately facilitate early, precise, and patient-specific pharmacological and non-pharmacological interventions to minimise CVD associated morbidity and mortality.

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.

Towards a treatment model for family therapy for schizophrenia in an urban African setting: Results from a qualitative study

Background: Family interventional programmes are effective adjuncts to pharmacotherapy in patients with schizophrenia. Modification in content of such programmes in response to local challenges is considered important, but has not been fully explored in Africa. Aims: To assess the feasibility and acceptability of an interventional family study for people with schizophrenia and their families in a socially deprived urban community in South Africa and to explore the contextual factors that could influence implementation of the intervention. Method: A psychiatric nurse facilitated semi-structured interviews with four multi-family groups, each comprising adult outpatients with schizophrenia and their caregivers. Six sessions were held per group. Thematic analysis was applied. Results: Three themes emerged: stigma and abuse; substance abuse comorbidity and caregiver burden of multiple stressors. Many of these stressors relate to the challenges of an impoverished urban environment. Conclusions: Multi-family groups with a psycho-educational and behaviour modification frame are acceptable. Negative symptoms are seen as protective in areas of community violence. Modification of traditional models of family therapy to include factors related to poverty, violence, caregiver burden, stigma and limited health care access should be considered in this setting.

Cognitive performance during the first year of treatment in first-episode schizophrenia: a case-control study.

BACKGROUND Several questions remain unanswered regarding the magnitude and time course of cognitive improvement in response to antipsychotic treatment. The purpose of this study was to assess changes in cognitive performance in antipsychotic-naive or minimally medicated patients with first-episode schizophrenia during the first 12 months of treatment, in a case-control design. Patients were treated with flupenthixol decanoate depot injection, according to a standard algorithm. The primary outcome measure was change in MATRICS Cognitive Consensus Battery (MCCB) composite score over 12 months. METHOD The sample comprised 92 patients and 100 healthy controls matched for age, sex, ethnicity and educational status. Cognitive function was assessed by means of the MCCB. RESULTS A mixed-effects model identified a significant group × time effect (p ≤ 0.0001) for the MCCB composite score, with patients showing a greater degree of change than the controls. For the other MCCB domains there were significant group × time effects at adjusted significance level for attention and vigilance (p ≤ 0.0001), visual learning (p ≤ 0.0001), verbal learning (p = 0.005) and working memory (p ≤ 0.0001), but not for reasoning and problem solving (p = 0.04), speed of processing (p = 0.03) and social cognition (p = 0.06). There were moderate correlations between change in MCCB composite score and change in symptomatology as assessed by Positive and Negative Syndrome Scale factor analysis-derived domains. CONCLUSIONS Substantial improvements in cognitive function were observed over and above a practice effect, and were significantly correlated with improvements in psychopathology and functionality.

Changes in body mass and metabolic profiles in patients with first-episode schizophrenia treated for 12 months with a first-generation antipsychotic

OBJECTIVES To assess changes in body mass and metabolic profiles in patients with first-episode schizophrenia receiving standardised, assured treatment and to identify predictors and moderators of the effects. METHODS We investigated the changes in body mass, fasting blood glucose and lipids in 107 largely antipsychotic naïve, first-episode schizophrenia patients who were treated according to a standard algorithm with long-acting injectable flupenthixol decanoate over 12 months. RESULTS Eighty-three (78%) participants completed the 12 months of treatment, and 104 (97%) received 100% of the prescribed injections during their participation. There were significant increases in BMI (P<.0001), waist circumference (P=0.0006) and triglycerides (P=0.03) and decrease in HDL (P=0.005), while systolic (P=0.7) and diastolic blood pressure (P=0.8), LDL (P=0.1), cholesterol (P=0.3), and glucose (P=0.9) values did not change over time. The triglyceride: HDL ratio increased by 91%. Change in BMI was only correlated with change in triglycerides (P=.008). The only significant predictor of BMI increase was non-substance abuse (P=.002). CONCLUSIONS The risks of weight gain and metabolic syndrome associated with antipsychotic treatment in first-episode schizophrenia are not restricted to second generation antipsychotics. This is a global problem, and developing communities may be particularly susceptible.