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Improvements are greatest in the earlier weeks of antipsychotic treatment of patients with non-resistant schizophrenia.
To address the early time-line for improvement with antipsychotics in treatment-resistant schizophrenia.
Randomised double-blind trials of antipsychotic medication in adult patients with treatment-resistant schizophrenia were investigated (last search June 2010). A series of meta-regression analyses were carried out to examine the effect of time on the average item scores in the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) at three or more distinct time points within the first 6 weeks of treatment.
Study duration varied from 4 weeks to 1 year and the definitions of treatment resistance as well as of treatment response were not necessarily consistent across 19 identified studies, resulting in highly variable rates of response (0–76%). The mean standardised baseline item score in the PANSS or BPRS was 3.4 (s.e. = 0.06) in the five studies included in the meta-regression analysis, with the average baseline Clinical Global Impression – Severity score being 5.2 (marked illness). For the pooled population treated with a range of antipsychotics (n = 1019), significant reductions in the mean item scores occurred during the first 4 weeks; improvements observed in later weeks were smaller and non-significant. In contrast, weekly improvement with clozapine was significant throughout (n = 356).
Our findings provide preliminary evidence that the majority of improvement with antipsychotics may occur relatively early. More consistent improvements with clozapine may be associated with a gradual titration. To further elucidate response patterns, future studies are needed to provide data over regular intervals during earlier stages of treatment.
This chapter presents studies of depression that use structural and functional imaging to examine the roles of different brain circuits and neurochemicals in the pathophysiology and treatment of the illness. Functional imaging studies have demonstrated changes in metabolism in the prefrontal cortex, anterior cingulate and amygdala in depression, and these findings are at least in part reversed with antidepressant treatment and cognitive behavioural therapy. Brain imaging in major depressive disorder has contributed to a better understanding of the pathophysiology of the illness from a neural system perspective as well as at the synaptic level. A recent meta-analysis of magnetic resonance imaging (MRI) studies in schizophrenia found that the most significant changes occur within the medial temporal lobe. The chapter also discusses neuroimaging in Alzheimer's disorder within the context of an emergent public health crisis concerning an illness with a relatively well-characterised histopathology.