Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

This paper presents a critical appraisal of resilience, a construct connoting the maintenance of positive adaptation by individuals despite experiences of significant adversity. As empirical research on resilience has burgeoned in recent years, criticisms have been levied at work in this area. These critiques have generally focused on ambiguities in definitions and central terminology; heterogeneity in risks experienced and competence achieved by individuals viewed as resilient; instability of the phenomenon of resilience; and concerns regarding the usefulness of resilience as a theoretical construct. We address each identified criticism in turn, proposing solutions for those we view as legitimate and clarifying misunderstandings surrounding those we believe to be less valid. We conclude that work on resilience possesses substantial potential for augmenting the understanding of processes affecting at-risk individuals. Realization of the potential embodied by this construct, however, will remain constrained without continued scientific attention to some of the serious conceptual and methodological pitfalls that have been noted by skeptics and proponents alike.

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The Construct of Resilience: A Critical Evaluation and Guidelines for Future Work

background The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. methods A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. results Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. conclusions The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.

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Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(07)61238-0.pdf

No health without mental health.

The dopamine hypothesis of schizophrenia has been one of the most enduring ideas in psychiatry. Initially, the emphasis was on a role of hyperdopaminergia in the etiology of schizophrenia (version I), but it was subsequently reconceptualized to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia (version II). However, these hypotheses focused too narrowly on dopamine itself, conflated psychosis and schizophrenia, and predated advances in the genetics, molecular biology, and imaging research in schizophrenia. Since version II, there have been over 6700 articles about dopamine and schizophrenia. We selectively review these data to provide an overview of the 5 critical streams of new evidence: neurochemical imaging studies, genetic evidence, findings on environmental risk factors, research into the extended phenotype, and animal studies. We synthesize this evidence into a new dopamine hypothesis of schizophrenia-version III: the final common pathway. This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function. It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia. The hypothesis has one major implication for treatment approaches. Current treatments are acting downstream of the critical neurotransmitter abnormality. Future drug development and research into etiopathogenesis should focus on identifying and manipulating the upstream factors that converge on the dopaminergic funnel point.

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The Dopamine Hypothesis of Schizophrenia: Version III—The Final Common Pathway

Clinical and health-related quality of life outcomes associated with olanzapine in patients with bipolar disorder as compared with haloperidol

Erratum: Efficacy of olanzapine in acute bipolar maniana double-blind, placebo-controlled study (Archives of General Psychiatry (2000) 47 (841-849))

In a recently published meta-analysis by Moteshafi et al., the authors concluded that ‘‘schizophrenia patients may bemore vulnerable to olanzapine-induced weight gain’’. In addition, they stated that schizophrenia patients have a higher incidence of treatment-emergent parkinsonism. These results are at odds with previous reports with other similar drugs andwith clinical experience. This led us to carefully review themethodology of the meta-analysis, to avoid potentially misleading clinical conclusions. In the mentioned metaanalysis, even though mean daily doses of olanzapine were comparable between groups (14.2mg/day vs 13.2mg/day), differences in total drug exposure (mean daily dose·duration of treatment) were quite different. In the schizophrenia group, drug exposure was 2.29 (2.7 g vs 1.18g) and 2.88 (3.83g vs 1.33g) times higher when considering the randomized controlled trials used for estimating weight change and parkinsonism incidence, respectively. Moreover, the report indicates that the authors were aware that trial duration was different between groups; hence, they stratified analyses by treatment duration and found out that weight gain was no longer significant, but did not consider this in their conclusions. Besides drug exposure which is highly relevant for a drug-tolerability analysis, a higher incidence of parkinsonism could be explained by a carryover effect (i.e. schizophrenic patients included in trials are more likely than bipolar patients to have been previously exposed to other antipsychotics for a longer time). In addition, the authors cite theCavazzoni et al. trial as having the same results as their own. However, Cavazzoni et al. concluded that olanzapine therapy does not increase the risk of treatment-emergent extrapyramidal symptoms (EPS) for patients with bipolar disorder. Specifically, they found that bipolar patients had more EPS when exposed to haloperidol than patients suffering from schizophrenia, even after adjusting by drug exposure, and found no differences between groupswhen treatedwith olanzapine. They only found higher rates of treatment-emergent parkinsonism in schizophrenia patients when analysing the Simpson Angus Scale data in the haloperidol controlled database. The authors make a good point in considering tolerability as an important issue when defining subgroups of patients to whom tailored treatment should be given; however, drug exposure is a crucial issue to consider when analysing drugemergent adverse effects. This meta-analysis has, therefore, substantial limitations and, in our view, may lead to unwarranted conclusions.

Mauricio Tohen

Papers

Clinical and health-related quality of life outcomes associated with olanzapine in patients with bipolar disorder as compared with haloperidol

Erratum: Efficacy of olanzapine in acute bipolar maniana double-blind, placebo-controlled study (Archives of General Psychiatry (2000) 47 (841-849))

Olanzapine in schizophrenia and affective disorders.

P.2.d.016 Efficacy of olanzapine monotherapy in the treatment of bipolar depression with varying degrees of manic symptoms

Olanzapine versus placebo in rapid-cycling bipolar disorder