Predictors of psychiatric hospitalization during 6 months of maintenance treatment with olanzapine long-acting injection: post hoc analysis of a randomized, double-blind study.

BACKGROUND: Hospitalization is a costly and distressing event associated with relapse during schizophrenia treatment. No information is available on the predictors of psychiatric hospitalization during maintenance treatment with olanzapine long-acting injection (olanzapine-LAI) or how the risk of hospitalization differs between olanzapine-LAI and oral olanzapine. This study aimed to identify the predictors of psychiatric hospitalization during maintenance treatment with olanzapine-LAI and assessed four parameters: hospitalization prevalence, incidence rate, duration, and the time to first hospitalization. Olanzapine-LAI was also compared with a sub-therapeutic dose of olanzapine-LAI and with oral olanzapine. METHODS: This was a post hoc exploratory analysis of data from a randomized, double-blind study comparing the safety and efficacy of olanzapine-LAI (pooled active depot groups: 405 mg/4 weeks, 300 mg/2 weeks, and 150 mg/2 weeks) with oral olanzapine and sub-therapeutic olanzapine-LAI (45 mg/4 weeks) during 6 months' maintenance treatment of clinically stable schizophrenia outpatients (n=1064). The four psychiatric hospitalization parameters were analyzed for each treatment group. Within the olanzapine-LAI group, patients with and without hospitalization were compared on baseline characteristics. Logistic regression and Cox's proportional hazards models were used to identify the best predictors of hospitalization. Comparisons between the treatment groups employed descriptive statistics, the Kaplan-Meier estimator and Cox's proportional hazards models. RESULTS: Psychiatric hospitalization was best predicted by suicide threats in the 12 months before baseline and by prior hospitalization. Compared with sub-therapeutic olanzapine-LAI, olanzapine-LAI was associated with a significantly lower hospitalization rate (5.2% versus 11.1%, p < 0.01), a lower mean number of hospitalizations (0.1 versus 0.2, p = 0.01), a shorter mean duration of hospitalization (1.5 days versus 2.9 days, p < 0.01), and a similar median time to first hospitalization (35 versus 60 days, p = 0.48). Olanzapine-LAI did not differ significantly from oral olanzapine on the studied hospitalization parameters. CONCLUSIONS: In clinically stable schizophrenia outpatients receiving olanzapine-LAI maintenance treatment, psychiatric hospitalization was best predicted by a history of suicide threats and prior psychiatric hospitalization. Olanzapine-LAI was associated with a significantly lower incidence of psychiatric hospitalization and shorter duration of hospitalization compared with sub-therapeutic olanzapine-LAI. Olanzapine-LAI did not differ significantly from oral olanzapine on hospitalization parameters.

Brain-Derived Neurotrophic Factor as a potential biomarker of cognitive recovery in schizophrenia

Brain-derived neurotrophic factor (BDNF) has been proposed as a biomarker of schizophrenia and, more specifically, as a biomarker of cognitive recovery. Evidence collected in this review indicates that BDNF is relevant in the pathophysiology of schizophrenia and could play a role as a marker of clinical response. BDNF has been shown to play a positive role as a marker in antipsychotic treatment, and it has been demonstrated that typical antipsychotics decrease BDNF levels while atypical antipsychotics maintain or increase serum BDNF levels. Furthermore, BDNF levels have been associated with severe cognitive impairments in patients with schizophrenia. Consequently, BDNF has been proposed as a candidate target of strategies to aid the cognitive recovery process. There is some evidence suggesting that BDNF could be mediating neurobiological processes underlying cognitive recovery. Thus, serum BDNF levels seem to be involved in some synaptic plasticity and neurotransmission processes. Additionally, serum BDNF levels significantly increased in schizophrenia subjects after neuroplasticity-based cognitive training. If positive replications of those findings are published in the future then serum BDNF levels could be definitely postulated as a peripheral biomarker for the effects of intensive cognitive training or any sort of cognitive recovery in schizophrenia. All in all, the current consideration of BDNF as a biomarker of cognitive recovery in schizophrenia is promising but still premature.

The natural hallucinogen 5-MeO-DMT, component of Ayahuasca, disrupts cortical function in rats: reversal by antipsychotic drugs

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen component of Ayahuasca, an Amazonian beverage traditionally used for ritual, religious and healing purposes that is being increasingly used for recreational purposes in US and Europe. 5MeO-DMT is of potential interest for schizophrenia research owing to its hallucinogenic properties. Two other psychotomimetic agents, phencyclidine and 2,5-dimethoxy-4-iodo-phenylisopropylamine (DOI), markedly disrupt neuronal activity and reduce the power of low frequency cortical oscillations (<4 Hz, LFCO) in rodent medial prefrontal cortex (mPFC). Here we examined the effect of 5-MeO-DMT on cortical function and its potential reversal by antipsychotic drugs. Moreover, regional brain activity was assessed by blood-oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). 5-MeO-DMT disrupted mPFC activity, increasing and decreasing the discharge of 51 and 35% of the recorded pyramidal neurons, and reducing (−31%) the power of LFCO. The latter effect depended on 5-HT1A and 5-HT2A receptor activation and was reversed by haloperidol, clozapine, risperidone, and the mGlu2/3 agonist LY379268. Likewise, 5-MeO-DMT decreased BOLD responses in visual cortex (V1) and mPFC. The disruption of cortical activity induced by 5-MeO-DMT resembles that produced by phencyclidine and DOI. This, together with the reversal by antipsychotic drugs, suggests that the observed cortical alterations are related to the psychotomimetic action of 5-MeO-DMT. Overall, the present model may help to understand the neurobiological basis of hallucinations and to identify new targets in antipsychotic drug development.

Neurocognition in schizophrenia: a study of the productivity and visibility of spanish authors

This paper provides a map of the scientific productivity of authors affiliated to a Spanish institution and who have addressed one of the most important current topics in schizophrenia: The study of cognitive performance. A search of the Web of Science yielded 125 articles that met the inclusion criteria. In order to provide a comprehensive overview of scientific productivity, we examine several bibliometric indicators, concerning both productivity and impact or visibility. The analysis also focuses on qualitative aspects of key theoretical importance, such as the kinds of cognitive functions that are most often assessed and the tests most widely used to evaluate them in clinical practice. The study shows that interest in the subject of cognitive function in schizophrenia has increased considerably in Spain since the beginning of this century. The results also highlight the need to standardize the type of tests to be used in the cognitive assessment of patients with schizophrenia.

Clinical consequences of switching from olanzapine to risperidone and vice versa in outpatients with schizophrenia: 36-month results from the worldwide schizophrenia outpatients health outcomes (W-SOHO) study

BACKGROUND: With many atypical antipsychotics now available in the market, it has become a common clinical practice to switch between atypical agents as a means of achieving the best clinical outcomes. This study aimed to examine the impact of switching from olanzapine to risperidone and vice versa on clinical status and tolerability outcomes in outpatients with schizophrenia in a naturalistic setting. METHODS: W-SOHO was a 3-year observational study that involved over 17,000 outpatients with schizophrenia from 37 countries worldwide. The present post hoc study focused on the subgroup of patients who started taking olanzapine at baseline and subsequently made the first switch to risperidone (n=162) and vice versa (n=136). Clinical status was assessed at the visit when the first switch was made (i.e. before switching) and after switching. Logistic regression models examined the impact of medication switch on tolerability outcomes, and linear regression models assessed the association between medication switch and change in the Clinical Global Impression-Schizophrenia (CGI-SCH) overall score or change in weight. In addition, Kaplan-Meier survival curves and Cox-proportional hazards models were used to analyze the time to medication switch as well as time to relapse (symptom worsening as assessed by the CGI-SCH scale or hospitalization). RESULTS: 48% and 39% of patients switching to olanzapine and risperidone, respectively, remained on the medication without further switches (p=0.019). Patients switching to olanzapine were significantly less likely to experience relapse (hazard ratio: 3.43, 95% CI: 1.43, 8.26), extrapyramidal symptoms (odds ratio [OR]: 4.02, 95% CI: 1.49, 10.89) and amenorrhea/galactorrhea (OR: 8.99, 95% CI: 2.30, 35.13). No significant difference in weight change was, however, found between the two groups. While the CGI-SCH overall score improved in both groups after switching, there was a significantly greater change in those who switched to olanzapine (difference of 0.29 points, p=0.013). CONCLUSION: Our study showed that patients who switched from risperidone to olanzapine were likely to experience a more favorable treatment course than those who switched from olanzapine to risperidone. Given the nature of observational study design and small sample size, additional studies are warranted.

Long-term functional improvements in the 2-year treatment of schizophrenia outpatients with olanzapine long-acting injection

BACKGROUND: Little is known about the long-term changes in the functioning of schizophrenia patients receiving maintenance therapy with olanzapine long-acting injection (LAI), and whether observed changes differ from those seen with oral olanzapine. METHODS: This study describes changes in the levels of functioning among outpatients with schizophrenia treated with olanzapine-LAI compared with oral olanzapine over 2 years. This was a secondary analysis of data from a multicenter, randomized, open-label, 2-year study comparing the long-term treatment effectiveness of monthly olanzapine-LAI (405 mg/4 weeks; n=264) with daily oral olanzapine (10 mg/day; n=260). Levels of functioning were assessed with the Heinrichs-Carpenter Quality of Life Scale. Functional status was also classified as 'good', 'moderate', or 'poor', using a previous data-driven approach. Changes in functional levels were assessed with McNemar's test and comparisons between olanzapine-LAI and oral olanzapine employed the Student's t-test. RESULTS: Over the 2-year study, the patients treated with olanzapine-LAI improved their level of functioning (per Quality of Life total score) from 64.0-70.8 (P<0.001). Patients on oral olanzapine also increased their level of functioning from 62.1-70.1 (P<0.001). At baseline, 19.2% of the olanzapine-LAI-treated patients had a 'good' level of functioning, which increased to 27.5% (P<0.05). The figures for oral olanzapine were 14.2% and 24.5%, respectively (P<0.001). Results did not significantly differ between olanzapine-LAI and oral olanzapine. CONCLUSION: In this 2-year, open-label, randomized study of olanzapine-LAI, outpatients with schizophrenia maintained or improved their favorable baseline level of functioning over time. Results did not significantly differ between olanzapine-LAI and oral olanzapine.

Analisis de un tratamiento individual de danza movimiento terapia en un caso crónico de esquizofrenia residual

En el siguiente estudio presento1 el análisis retrospectivo de un tratamiento individual de 17 sesiones de danza movimiento terapia en un caso crónico de una mujer de 59 años, institucionalizada, con un diagnóstico de esquizofrenia residual. Mi objetivo es evaluar la evolución y conclusión del tratamiento, con el fin de encontrar puntualizaciones de interés en la técnica de la DMT para pacientes con diagnósticos de psicosis y seguir construyendo y fortaleciendo la teoría y técnica de la DMT en esta población. Mis influencias teórico-técnicas provienen principalmente de los modelos de trabajo con pacientes psiquiátricos de Chaiklin y Schmais, S. (1979), Chaiklin, S. (1981), Jones (1992) y Liebowitz (1992). Utilicé las técnicas de la improvisación, el reflejo empático (Sandel, S. 1995), la verbalización (Stark & Lohn, 1995), la imagen, la metáfora y el símbolo (Sandel, S. 1995) y las enseñanzas del sistema de análisis del movimiento de Kestenberg (1999). Las aportaciones sobre creatividad de Brainsky (1988) y Pinchas Noy (1968-1969) me fueron de gran ayuda. Para el análisis triangulo información de varias fuentes: diarios de campo realizados durante el tratamiento junto con sus señalamientos producto de supervisiones y tutorías, la entrevista inicial y final a la paciente y un video analizado con la paciente y posteriormente estudiado bajo la óptica del sistema de análisis del movimiento de Kestenberg (Kestenberg y otros, 1999). Vivencio a través de mi paciente la utilidad y éxito de la DMT en la psicosis y las técnicas que nos permiten acercarnos a esta población. La DMT trabaja la estructura, no exclusivamente el fenómeno psicótico; aunque no se transforme la personalidad se fortalece, permitiéndole al sujeto vivir mejor en su condición, ser más autónomo, eficaz, feliz y móvil. La condición perse del proceso terapéutico con un psicótico es establecer una relación terapéutica para la cual es necesario entender en el cuerpo y en la mente que el funcionamiento de un psicótico no es el mismo que el de un neurótico; la barrera neurótica del terapeuta ha de sobrepasarse para lograr la fusión simbiótica que permitirá el bottom-up del psicótico. Los objetivos de trabajo en el caso individual son: integrar y desarrollar la unidad psiquesoma, contactar y expresar emociones, desarrollar las habilidades interpersonales y sociales, expandir el universo simbólico y desarrollar el movimiento espontáneo y la creatividad. Las fases del tratamiento son: los acercamientos y observaciones preliminares; la exploración del cuerpo, identificación de los focos de trabajo y comienzo de la ampliación del movimiento; la profundización y nacimiento del símbolo en la terapia y la consolidación de los avances y cierre del tratamiento. La técnica principal, es el reflejo empático del movimiento y la emoción en la improvisación y otras útiles, el masaje, automasaje, relajación, el dibujo, entre otras.

Características fenotípicas de personalidad y neuropsicológicas en padres no afectados de pacientes esquizofrénicos

Introducció. Actualment, està àmpliament acceptat que l'esquizofrènia posseeix una etiologia multifactorial i que existeix una complexa interacció entre factors genètics i factors ambientals. Amb l'objectiu de coneixerà quins són els mecanismes etiològics i patofisiològics que determinen el trastorn una part de la investigaci6 s 'ha centrat, en els últims anys, en la detecció de marcadors de vulnerabilitat en subjectes amb risc al trastorn. Aquesta vulnerabilitat, denominada 'esquizotipia', es pot identificar en subjectes clínicament no afectats. Objectiu. L'objectiu d'aquesta investigació s'ha dirigit a intentar contestar a alguns interrogants que encara no tenen resposta. Per exemple, per què alguns familiars, essent portadors del genotip esquizofrènic, no han presentat mai la malaltia?, existeixen formes esquizotípiques de menor risc per a la presentació del trastorn?, poden alguns patrons esquizotípics 'ajudar' a que la vulnerabilitat es mantingui latent i no es manifesti en forma de trastorn? En termes generals, l'estudi s'ha centrat en la identificació de marcadors de vulnerabilitat dels trastorns de l'espectre esquizofrènic en pares no afectats de pacients amb esquizofrènia (subjectes d'edats avançades amb poca probabilitat de presentar el trastorn) comparats amb pares normals de subjectes normals. Metodologia. S' han avaluat 26 parelles de pares no afectats de pacients amb esquizofrènia i 26 parelles de pares normals de subjectes normals (n= 104) en variables de personalitat i comportamentals (esquizotipia psicomètrica -O-LIFE-, trastorns de personalitat -Qüestionari d'avaluació IPDE-, psicopatologia general -SCL-90- i lloc de control -MHLC-) i variables neuropsicològiques (dèficit atencional -CPT-IP-, funció executiva -TMT part B- i memòria i aprenentatge verbal -CVLT-). Resultats. Els pares dels pacients esquizofrènics, comparats amb els controls, mostren significativament puntuacions mes altes al factor d'anhedònia introvertida, al trastorn paranoide de la personalitat i al trastorn per evitació de la personalitat, més característiques de psicopatologia general i un major lloc de control intern relacionat amb la salut. També realitzen mes errors d'omissió en la tasca atencional, presenten una major interferència proactiva al test de memòria i aprenentatge verbal i mostren una tendència a dedicar mes temps a completar la tasca executiva. Els resultats mostren que les associacions entre les variables de personalitat i les neuropsicològiques són de poca magnitud i les diferències entre ambdós grups no segueixen un patró clarament determinat. Conclusions. Els pares dels pacients esquizofrènics presenten més trets esquizotípics negatius que els pares del subjectes normals. L'anhedònia introvertida podria considerar-se com una forma de menor risc a l'esquizofrènia ja que s'evidencia en subjectes (pares) d'edats avançades que ja han superat l'edat de risc i amb poca probabilitat de presentar mai el trastorn. Tanmateix, es confirma que el trastorn paranoide de la personalitat forma part dels trastorns de l'espectre esquizofrènic. Els pares dels pacients atribueixen un major pes i la internalització i al poder dels altres en relació a l'estat de salut, i en general, presenten més característiques psicopatològiques que el grup control. Quant a les variables neuropsicològiques, els pares dels pacients realitzen pitjor la tasca atencional, són més lents en l'anticipació, planificació i flexibilitat de les respostes en el test executiu. Els indicadors de memòria i aprenentatge verbal no discriminen a ambdós grups, i únicament els pares dels pacients presenten una major interferència proactiva. Finalment, el patró de personalitat i el neuropsicològic corresponen a dos fenotips diferents relacionats amb l'esquizofrènia que no es troben íntimament units en subjectes amb aquestes característiques.