Bonginkosi Chiliza

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.

Predictors of long-term outcome in schizophrenia.

Purpose of review Further clarification of factors predicting the outcome in schizophrenia is needed. The present review examines recent research into some of these predictors, focusing on insight, duration of untreated psychosis, cognition and early treatment response. It also addresses the need for standard outcome measures. Recent findings There is good evidence that poor insight predicts poor outcome, although perhaps not simply as a consequence of poor compliance. Further support is provided for a link between duration of untreated psychosis and long-term outcome. The relationship between cognition and outcome is complex, with specific cognitive deficits apparently predicting particular outcome domains. Early treatment response is closely related to long-term outcome. Outcome studies may be flawed by sample selection bias, and a lack of standardized outcome measures. Summary Several predictors are potentially modifiable, indicating that they should be targets for therapeutic intervention. More carefully designed studies are needed. Recently proposed criteria for remission are helpful, and should facilitate cross-sample comparisons.

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.

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.

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.

Language, culture, and task shifting – an emerging challenge for global mental health

Language is at the heart of mental health care. Many high-income countries have sophisticated interpreter services, but in low- and middle-income countries there are not sufficient professional services, let alone interpreter services, and task shifting is used. In this article, we discuss this neglected issue in the context of low- and middle-income countries, where task shifting has been suggested as a solution to the problem of scarce mental health resources. The large diversity of languages in low- and middle-income countries, exacerbated by wide-scale migration, has implications for the scale-up of services. We suggest that it would be useful for those who are working innovatively to develop locally delivered mental health programmes in low- and middle-income countries to explore and report on issues of language and how these have been addressed. We need to know more about local challenges, but also about local solutions which seem to work, and for this we need more information from the field than is currently available.Language is at the heart of mental health care. Many high-income countries have sophisticated interpreter services, but in low- and middle-income countries there are not sufficient professional services, let alone interpreter services, and task shifting is used. In this article, we discuss this neglected issue in the context of low- and middle-income countries, where task shifting has been suggested as a solution to the problem of scarce mental health resources. The large diversity of languages in low- and middle-income countries, exacerbated by wide-scale migration, has implications for the scale-up of services. We suggest that it would be useful for those who are working innovatively to develop locally delivered mental health programmes in low- and middle-income countries to explore and report on issues of language and how these have been addressed. We need to know more about local challenges, but also about local solutions which seem to work, and for this we need more information from the field than is currently available.

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.