Changing the Antipsychotic in Early Nonimprovers to Amisulpride or Olanzapine: Randomized, Double-Blind Trial in Patients With Schizophrenia.

BACKGROUND AND HYPOTHESIS: Meta-analyses have shown that the majority of patients with schizophrenia who have not improved after 2 weeks of treatment with an antipsychotic drug are unlikely to fully respond later. We hypothesized that switching to another antipsychotic with a different receptor binding profile is an effective strategy in such a situation. STUDY DESIGN: In total, 327 inpatients with an acute exacerbation of schizophrenia were randomized to double-blind treatment with either olanzapine (5-20 mg/day) or amisulpride (200-800 mg/day). Those patients who had not reached at least 25% Positive-and-Negative-Syndrome-Scale (PANSS) total score reduction from baseline after 2 weeks (the "non-improvers") were rerandomized double-blind to either staying on the same compound ("stayers") or to switching to the other antipsychotic ("switchers") for another 6 weeks. The primary outcome was the difference in the number of patients in symptomatic remission between the combined "switchers" and the "stayers" after 8 weeks of treatment, analyzed by logistic regression. STUDY RESULTS: A total of 142 nonimprovers were rerandomized at week two. 25 (45.5 %) of the 'stayers' compared to 41 (68.3 %) of the "switchers" reached remission at endpoint (p = .006). Differences in secondary efficacy outcomes were not significant, except for the PANSS negative subscore and the Clinical-Global-Impression-Scale. "Switchers" and "stayers" did not differ in safety outcomes. CONCLUSIONS: Switching "non-improvers" from amisulpride to olanzapine or vice-versa increased remission rates and was safe. The superiority in the primary outcome was, however, not paralleled by significant differences in most secondary efficacy outcomes and the effect was only apparent at the last visit making replications of longer duration necessary.

Sick leave duration as a potential marker of functionality and disease severity in depression.

Objective: To discuss the impact of depression on work and how depression-related sick leave duration could be a potential indicator and outcome for measuring functionality in depression.Methods: Our review was based on a literature search and expert opinion that emerged during a virtual meeting of European psychiatrists that was convened to discuss this topic.Results: Current evidence demonstrates that depression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditions. A wide variety of pharmacological and non-pharmacological treatments and work-based interventions are effective in reducing depression-related sick leave duration and/or facilitating return to work. Recent real-world evidence showed that patients treated with antidepressant monotherapy appear to recover their working life faster than those receiving combination therapy. Although depression-related sick leave duration was found to correlate with severity of depressive symptoms, it cannot be used alone as a viable marker for disease severity.Conclusions: Given its multifactorial nature, depression-related sick leave duration is not on its own a viable outcome measure of depression severity but could be used as a secondary outcome alongside more formal severity measures and may also represent a useful measure of functionality in depression. Key pointsDepression in the working population and depression-related sick leave have a profound economic impact on societyDepression-related sick leave duration is influenced by multiple disease-, patient- and work-related factors, together with societal attitudes towards depression and socioeconomic conditionsA wide variety of pharmacological and non-pharmacological treatments and work-based interventions have been shown to be effective in reducing depression-related sick leave duration and/or facilitating return to workIn terms of pharmacological intervention, recent real-world evidence has shown that patients treated with antidepressant monotherapy are able to recover their working life faster than those treated with combination therapyAlthough depression-related sick leave duration has been shown to correlate with severity of depressive symptoms, it is not a viable outcome measure of depression severity on its own, but could be used as secondary outcome alongside more formal clinician- and patient-rated severity measuresDepression-related sick leave duration may, however, represent a viable outcome for measuring functionality in depression.

Morphopathological changes in obsessive-compulsive disorder.

The pathophysiology of the obsessive-compulsive disorder (OCD) has been studied for many years using several structural magnetic resonance imaging, discovering that the anomalies of function and structure of the brain are widespread, they involve different areas, structures and circuits with a complex interconnectivity. More than that, these anomalies cover all the life of a patient, from early childhood, due to variations of developmental stages until adult life. The research is highly important also because OCD has a major hereditary factor, with the phenotype variance between 27-47% due to hereditary factors. Under this paper, that follows last 10 years studies in this area, we will find some relevant findings consisting on neuroanatomic changes, the morphology findings of striatum, globus pallidus and thalamus, the blood flow circuit changes in various regions of the brain, brain connectivity and various correlations of them. Not to forget that OCD must be understand as an emotional disorder but in the same time as a cognitive disorder too. This approach highlights the abnormalities that have been found in brain regions involved in the cognitive and emotional behavior, as for example: extended temporal, parietal, and occipital regions, anterior cingulate, frontal gyrus, amygdala.

Treatment effectiveness in patients with schizophrenia as measured by the ASSESS battery - first longitudinal data.

BACKGROUND: Effective pharmacological treatment with a favorable side-effect profile increases treatment adherence and is therefore very important for patients with schizophrenia. Psychiatrists need easy to use and reliable assessments instruments to evaluate treatment effectiveness in their patients. SUBJECTS AND METHODS: A group of European leading psychiatrists have proposed a framework for the assessment of treatment effectiveness in patients with schizophrenia - the ASSESS battery (The ASseSsment of EffectivenesS in Schizophrenia Battery) which evaluates the effectiveness of treatment during both the remission and the relapse periods. ASSESS includes: 10 items of Positive and Negative Symptoms Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), Medication Satisfaction Questionnaire (MSQ), and Personal and Social Performance Scale (PSP). The battery assesses five domains: symptomatic remission and retention of treatment, affective symptoms, cognitive functioning, treatment satisfaction and personal and social functioning. The aim of the present study was to evaluate the applicability of ASSESS in real world practice. RESULTS: The variations of the PANSS items rated during the study indicate a significant improvement of psychopathology. A similar improvement was observed in cognition, social functioning and treatment satisfaction as shown by BACS, PSP and MSQ scales. Cognitive impairment, personal and social functioning, and treatment satisfaction were correlated with the remission or augmentation of positive symptoms. CONCLUSIONS: This pilot study revealed that ASSESS is easy to apply in clinical practice and is a suitable tool for psychiatrists since it covers all the relevant aspects of the course of schizophrenia in a compact form.

Brain derived neurotrophic factor (BDNF) levels in depressed women treated with open-label escitalopram.

BACKGROUND: Recent studies suggest the important role of brain derived neurotrophic factor (BDNF) in the etiopathogenesis of major depressive disorder (MDD) and the mechanism of action of antidepressants. This study aimed to correlate serum levels of BDNF and clinical symptoms in patients with MDD before and after 6 months treatment with escitalopram. SUBJECTS AND METHODS: Twenty women diagnosed with MDD and 20 aged-matched healthy female controls were recruited. The patients received escitalopram 10-20 mg/day. BDNF serum levels were measured at inclusion, week 4, week 12 and week 24. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used to assess the severity of depressive symptoms and the clinical evolution of patients. Statistical analysis was performed using both observed cases and last observation carried forward. RESULTS: At baseline, low serum levels of BDNF were associated with MDD. In women with MDD, escitalopram seems to have a positive effect on BDNF serum levels in parallel with the clinical response. CONCLUSIONS: This study suggests that a good clinical evolution under treatment with escitalopram might be associated with increases of BDNF levels in female patients.

A randomized controlled trial of allopurinol vs. placebo added on to antipsychotics in patients with schizophrenia or schizoaffective disorder.

Adenosine agonists produce behavioral effects similar to dopamine antagonists, hence increasing adenosine levels might improve symptoms of schizophrenia. This hypothesis is supported by three single-site studies indicating that allopurinol, which increases adenosine levels, improved symptoms in patients with schizophrenia. We performed a multi-center, 8-week RCT of allopurinol vs. placebo added to anti-psychotic medications in 248 patients with schizophrenia or schizoaffective disorder. Both groups showed improvement in the PANSS (effect size 1.13) and in clinical and cognitive measures. No difference was observed between groups in primary (t=0.01, p=0.992) or secondary outcome measures. These findings do not support allopurinol as a treatment for schizophrenia.

Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative.

CONTEXT: There is limited information on the prevalence and correlates of bipolar spectrum disorder in international population-based studies using common methods. OBJECTIVES: To describe the prevalence, impact, patterns of comorbidity, and patterns of service utilization for bipolar spectrum disorder (BPS) in the World Health Organization World Mental Health Survey Initiative. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional, face-to-face, household surveys of 61,392 community adults in 11 countries in the Americas, Europe, and Asia assessed with the World Mental Health version of the World Health Organization Composite International Diagnostic Interview, version 3.0, a fully structured, lay-administered psychiatric diagnostic interview. MAIN OUTCOME MEASURES: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) disorders, severity, and treatment. RESULTS: The aggregate lifetime prevalences were 0.6% for bipolar type I disorder (BP-I), 0.4% for BP-II, 1.4% for subthreshold BP, and 2.4% for BPS. Twelve-month prevalences were 0.4% for BP-I, 0.3% for BP-II, 0.8% for subthreshold BP, and 1.5% for BPS. Severity of both manic and depressive symptoms as well as suicidal behavior increased monotonically from subthreshold BP to BP-I. By contrast, role impairment was similar across BP subtypes. Symptom severity was greater for depressive episodes than manic episodes, with approximately 74.0% of respondents with depression and 50.9% of respondents with mania reporting severe role impairment. Three-quarters of those with BPS met criteria for at least 1 other disorder, with anxiety disorders (particularly panic attacks) being the most common comorbid condition. Less than half of those with lifetime BPS received mental health treatment, particularly in low-income countries, where only 25.2% reported contact with the mental health system. CONCLUSIONS: Despite cross-site variation in the prevalence rates of BPS, the severity, impact, and patterns of comorbidity were remarkably similar internationally. The uniform increases in clinical correlates, suicidal behavior, and comorbidity across each diagnostic category provide evidence for the validity of the concept of BPS. Treatment needs for BPS are often unmet, particularly in low-income countries.

Markers of vulnerability in schizophrenia.

Vulnerability in schizophrenia is an integrative concept, which tries to explain the development of schizophrenia as an interaction between different individual susceptibility factors and environmental risk factors. Vulnerability markers used in genetic studies include biochemical indicators, neuroanatomical, neurophysiologic, and cognitive abnormalities. Among those, the most extensive studied markers were: evoked potentials, smooth pursuit eye movements, and attentional deficits. Some of the potential indicators presented in this paper satisfy most of the criteria necessary for a vulnerability marker, but none meets all of them. Nevertheless, they represent important markers of risk to schizophrenia.