Who need antipsychotic medication in the earliest stage of psychosis? A reconsideration of benefits, risks, neurobiology and ethics in the era of early intervention

Orygen Youth Health, 35 Poplar Road Locked Bag 10, Parkville, Victoria 3052, Australia.
Schizophrenia Research (Impact Factor: 3.92). 03/2010; 119(1-3):1-10. DOI: 10.1016/j.schres.2010.02.1071
Source: PubMed


In recent years, early intervention services have attempted to identify people with a first episode of psychosis as early as possible, reducing the duration of untreated psychosis and changing the timing of delivery of interventions. The logic of early intervention is based partly on accessing people in a more treatment responsive stage of illness in which psychosocial damage is less extensive, and partly on remediating a putatively active process of neuroprogression that leads to pathophysiological, symptomatic and structural changes, hence improving symptomatic and functional outcomes. However, as in other areas of health care, earlier identification of new patients may mean that different treatment approaches are indicated. The corollary of early detection is that the sequence and complexion of treatment strategies for first episode psychosis has been revaluated. Examples include the minimal effective dosage of antipsychotic medication and the content of psychosocial interventions. With the substantial reductions of DUP now seen in many early psychosis services, based on clinical staging and stepped care principles, it is even possible that the immediate introduction of antipsychotic medication may not be necessary for all first episode psychosis cases, but that potentially safer interventions, which may be more acceptable to many patients, such as comprehensive psychosocial intervention, may constitute effective treatment at least for a subgroup of patients. In this paper, we review this theoretical background and describe a randomised controlled trial currently underway at the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne designed to test outcomes for first episode psychosis patients in response to two different treatments: intensive psychosocial intervention plus antipsychotic medication versus intensive psychosocial intervention plus placebo. This is a theoretically and pragmatically novel study in that it will provide evidence as to whether intensive psychosocial intervention alone is sufficient for a subgroup of first episode psychosis patients in a specialised early intervention service, and provide a test of the heuristic clinical staging model. By experimentally manipulating duration of untreated psychosis, the study will also provide a methodologically strong test of the effect of delaying the introduction of antipsychotic medication, as well as helping to disentangle the effects of antipsychotic medications and the putative neurobiological processes associated with brain changes and symptom profiles in the early phase of psychotic disorders. The study has been carefully crafted to satisfy critical ethical demands in this challenging research domain.

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    • "Our results also support the suggestion made by other authors of prescribing antioxidants to treat schizophrenia (Mahadik et al., 2006; Dean et al., 2011; Reddy et al., 2011) due to the involvement of oxidative stress in several processes occurring over the course of the illness including cognitive impairment. We underline that these antioxidants could be used in the very early stages, as a more benign form of treatment , attempting to delay the introduction of antipsychotic medication in early onset patients and, thereby, avoid the adverse events of such medications for as long as possible as suggested by some other authors (Francey et al., 2010), and also combining their effects with those of antipsychotic medication, ideally enabling lower doses to be used in children and adolescents. However, for this approach to be adopted in routine practice, further research is needed to demonstrate the usefulness of antioxidants in schizophrenia. "
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    ABSTRACT: The objective of the study is to examine the association of baseline total antioxidant status (TAS) and glutathione (GSH) levels with short- and long-term cognitive functioning in patients with early onset first-episode psychosis, comparing affective and non-affective psychoses. We analysed 105 patients with an early onset-first episode psychosis (age 9–17 years) and 97 healthy controls. Blood samples were taken at admission for measurement of TAS and GSH, and cognitive performance was assessed at baseline and at 2 years of follow-up. Regression analysis was used to assess the relationship between TAS/GSH levels at baseline and cognitive performance at both time points, controlling for confounders. Baseline TAS and GSH levels were significantly lower in patients than healthy controls. In patients, baseline TAS was positively associated with the global cognition score at baseline (p = 0.048) and two years later (p = 0.005), while TAS was not associated with cognitive functioning in healthy controls. Further, baseline TAS in patients was specifically associated with the memory domain at baseline and with the memory and attention domains two years later. Stratifying by affective and non-affective psychoses, significant associations were only found between TAS and cognition in the non-affective psychosis group. Baseline GSH levels were not associated with cognitive functioning at either time point in either group. The antioxidant defence capacity in early onset first-episode psychotic patients is directly correlated with global cognition at baseline and at 2 years of follow-up, especially in non-affective psychosis.
    Schizophrenia Research 06/2014; 156(1). DOI:10.1016/j.schres.2014.03.025 · 3.92 Impact Factor
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    • "Another advantage may be that LAI antipsychotics can improve patient's qualityof-life overtime with more possibilities to meet friends and family, to live a more stable and independent life, outside the psychiatric hospital [40]. Patients with schizophrenia are more sensitive to adverse drug effects during the first few years of the illness [41] [42] [43]; therefore, the low incidence of adverse events caused by low variation in peak and trough levels of LAI antipsychotics may have additional benefits for pharmacological compliance during the critical period. Some people argued that the best time to prescribe LAI antipsychotics is just prior to discharge. "
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    08/2012; 2012(33, supplement):560836. DOI:10.1155/2012/560836
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    • "Staging models for SZ (Agius et al., 2010; Wood et al., 2011) and bipolar disorder (BD) (Vieta et al., 2011; Kapczinski et al., 2009a,b; Berk et al., 2007) have been proposed in order to personalize and optimize treatments (Berk et al., 2009). The logic of staging is based on accessing people to give them different treatment approaches according to pathophysiological, symptomatic and structural changes (Francey et al., 2010). "
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