Mauricio Tohen

Bio: Mauricio Tohen is an academic researcher from University of New Mexico. The author has contributed to research in topics: Bipolar disorder & Olanzapine. The author has an hindex of 95, co-authored 464 publications receiving 32214 citations. Previous affiliations of Mauricio Tohen include University of Minnesota & University of Alabama at Birmingham.

Efficacy of Olanzapine and Olanzapine-Fluoxetine Combination in the Treatment of Bipolar I Depression

Abstract: Background Despite the longer duration of the depressive phase in bipolar disorder and the frequent clinical use of antidepressants combined with antipsychotics or mood stabilizers, relatively few controlled studies have examined treatment strategies for bipolar depression. Objective To examine the use of olanzapine and olanzapine-fluoxetine combination in the treatment of bipolar I depression. Design Double-blind, 8-week, randomized controlled trial. Setting Eighty-four sites (inpatient and outpatient) in 13 countries. Patients A total of 833 randomized adults with bipolar I depression with a Montgomery-Asberg Depression Rating Scale (MADRS) score of at least 20. Intervention Patients were randomly assigned to receive placebo (n = 377); olanzapine, 5 to 20 mg/d (n = 370); or olanzapine-fluoxetine combination, 6 and 25, 6 and 50, or 12 and 50 mg/d (n = 86). Main Outcome Measure Changes in MADRS total scores using mixed-effects model repeated-measures analyses. Results During all 8 study weeks, the olanzapine and olanzapine-fluoxetine groups showed statistically significant improvement in depressive symptoms vs the placebo group ( P Conclusions Olanzapine is more effective than placebo, and combined olanzapine-fluoxetine is more effective than olanzapine and placebo in the treatment of bipolar I depression without increased risk of developing manic symptoms.

Antipsychotic drug effects on brain morphology in first-episode psychosis

Abstract: Background Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described. Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome. This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia. Objective To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patientsandthat gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition. Design Longitudinal, randomized, controlled, multisite, double-blind study. Patients treated and followed up for up to 104 weeks. Neurocognitive and magnetic resonance imaging (MRI) assessments performed at weeks 0 (baseline), 12, 24, 52, and 104. Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI, psychopathologic, and neurocognitive outcomes. Setting Fourteen academic medical centers (United States, 11; Canada, 1; Netherlands, 1; England, 1). Participants Patients with first-episode psychosis (DSM-IV) and healthy volunteers. Interventions Random allocation to a conventional antipsychotic, haloperidol (2-20 mg/d), or an atypical antipsychotic, olanzapine (5-20 mg/d). Main Outcome Measures Brain volume changes assessed by MRI. Results Of 263 randomized patients, 161 had baseline and at least 1 postbaseline MRI evaluation. Haloperidol-treated patients exhibited significant decreases in gray matter volume, whereas olanzapine-treated patients did not. A matched sample of healthy volunteers (n = 58) examined contemporaneously showed no change in gray matter volume. Conclusions Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes. Haloperidol was associated with significant reductions in gray matter volume, whereas olanzapine was not. Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated. The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine.

One hundred years of schizophrenia: a meta-analysis of the outcome literature.

Abstract: Objective This study was undertaken to assess the twentieth-century literature on outcome in schizophrenia for historical trends that might be associated with changes in diagnostic and therapeutic practice and to test the hypothesis that both improved biological treatment and changes in diagnostic criteria have influenced outcome. Method Meta-analysis of the international literature on outcome in schizophrenia or dementia praecox from 1895 to 1992 identified 821 studies; 320 of these, with 51,800 subjects in 368 cohorts, met the inclusion criteria for the study. Results Only 40.2% of patients were considered improved after follow-ups averaging 5.6 years (range = 1-40). Outcome was significantly better when patients were diagnosed according to systems with broad criteria (46.5% were improved) or undefined criteria (41.0% were improved) rather than narrow criteria (27.3% were improved). The proportion of patients who improved increased significantly after mid-century (for 1956-1985 versus 1895-1955, 48.5% versus 35.4%), probably reflecting improved treatment as well as a broadened concept of schizophrenia. However, in the past decade, the average rate of favorable outcome has declined to 36.4%, perhaps reflecting the re-emergence of narrow diagnostic concepts. Conclusions Overall, less than half of patients diagnosed with schizophrenia have shown substantial clinical improvement after follow-up averaging nearly 6 years. Despite considerable gains in improvement rates after mid-century, there has been a decline since the 1970s. These historical changes probably reflect improved treatment, shifts in diagnostic criteria, and selection bias related to changes in health care.

Efficacy of olanzapine in acute bipolar mania: A double-blind, placebo-controlled study

Abstract: Background We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania Methods Four-week, randomized, double-blind, parallel study A total of 115 patients with aDSM-IVdiagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg/d (n = 55), or placebo (n = 60) The primary efficacy measure was the Young–Mania Rating Scale (Y-MRS) total score Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change Results Olanzapine-treated patients demonstrated a statistically significant greater mean (± SD) improvement in Y-MRS total score than placebo-treated patients (−148 ± 125 and −81 ± 127, respectively;P Conclusion Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated

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

Abstract: 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.

Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia

Abstract: 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.

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

Abstract: 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.