Class effect of pharmacotherapy in bipolar disorder: fact or misbelieff?

BACKGROUND: Anecdotal reports suggests that most clinicians treat medications as belonging to a class with regard to all therapeutic indications; this means that the whole 'class' of drugs is considered to possesses a specific therapeutic action. The present article explores the possible existence of a true 'class effect' for agents available for the treatment of bipolar disorder. METHODS: We reviewed the available treatment data from randomized controlled trials (RCTs) and explored 16 'agent class'/'treatment issue' cases for bipolar disorder. Four classes of agents were examined: first-generation antipsychotics (FGAs), second-generation antipsychotics (SGAs), antiepileptics and antidepressants, with respect to their efficacy on four treatment issues of bipolar disorder (BD) (acute mania, acute bipolar depression, maintenance against mania, maintenance against depression). RESULTS: From the 16 'agent class'/' treatment issue' cases, only 3 possible class effects were detected, and they all concerned acute mania and antipsychotics. Four effect cases have not been adequately studied (FGAs against acute bipolar depression and in maintenance protection from depression, and antidepressants against acute mania and protection from mania) and they all concern treatment cases with a high risk of switching to the opposite pole, thus research in these areas is poor. There is no 'class effect' at all concerning antiepileptics. CONCLUSIONS: The available data suggest that a 'class effect' is the exception rather than the rule in the treatment of BD. However, the possible presence of a 'class effect' concept discourages clinicians from continued scientific training and reading. Focused educational intervention might be necessary to change this attitude.

Una aproximación a las funciones ejecutivas en el trastorno del espectro autista

Introducción: La hipótesis psicológica de la disfunción ejecutiva desempeña un papel crucial para explicar el fenotipo conductual de las personas con trastornos del espectro autista (TEA), relacionada también con otras hipótesis como el déficit en teoría de la mente o la hipótesis de la coherencia central débil. Sin embargo, ninguna de estas hipótesis son mutuamente excluyentes y los comportamientos que tienen su origen en alguna de esas tres hipótesis están también moldeados y mantenidos por otros procesos y factores. Desarrollo: Este artículo revisa la manifestación conductual y el estado de la investigación sobre las funciones ejecutivas en personas con TEA y su impacto en las habilidades de planificación, de flexibilidad mental y cognitiva, generatividad, inhibición de respuesta, habilidades mentalistas y sentido de la actividad. Conclusión: Aunque la disfunción ejecutiva ha ido ganando peso como hipótesis explicativa en las personas con TEA, persisten algunas dificultades relevantes que precisan de mayor y más detallada investigación. Por otro lado, son muy escasos los programas de intervención con eficacia demostrada que minimicen los efectos de la disfunción ejecutiva en el autismo.

Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis.

Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with an antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression. Comment in The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlEfficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis--results to be interpreted with caution.

Staging Bipolar Disorder.

The purpose of this study was to analyze the evidence supporting a staging model for bipolar disorder. The authors conducted an extensive Medline and Pubmed search of the published literature using a variety of search terms (staging, bipolar disorder, early intervention) to find relevant articles, which were reviewed in detail. Only recently specific proposals have been made to apply clinical staging to bipolar disorder. The staging model in bipolar disorder suggests a progression from prodromal (at-risk) to more severe and refractory presentations (Stage IV). A staging model implies a longitudinal appraisal of different aspects: clinical variables, such as number of episodes and subsyndromal symptoms, functional and cognitive impairment, comorbidity, biomarkers, and neuroanatomical changes. Staging models are based on the fact that response to treatment is generally better when it is introduced early in the course of the illness. It assumes that earlier stages have better prognosis and require simpler therapeutic regimens. Staging may assist in bipolar disorder treatment planning and prognosis, and emphasize the importance of early intervention. Further research is required in this exciting and novel area.

Stage managing bipolar disorder.

OBJECTIVES: Clinical staging is widespread in medicine - it informs prognosis, clinical course, and treatment, and assists individualized care. Staging places an individual on a probabilistic continuum of increasing potential disease severity, ranging from clinically at-risk or latency stage through first threshold episode of illness or recurrence, and, finally, to late or end-stage disease. The aim of the present paper was to examine and update the evidence regarding staging in bipolar disorder, and how this might inform targeted and individualized intervention approaches. METHODS: We provide a narrative review of the relevant information. RESULTS: In bipolar disorder, the validity of staging is informed by a range of findings that accompany illness progression, including neuroimaging data suggesting incremental volume loss, cognitive changes, and a declining likelihood of response to pharmacological and psychosocial treatments. Staging informs the adoption of a number of approaches, including the active promotion of both indicated prevention for at-risk individuals and early intervention strategies for newly diagnosed individuals, and the tailored implementation of treatments according to the stage of illness. CONCLUSIONS: The nature of bipolar disorder implies the presence of an active process of neuroprogression that is considered to be at least partly mediated by inflammation, oxidative stress, apoptosis, and changes in neurogenesis. It further supports the concept of neuroprotection, in that a diversity of agents have putative effects against these molecular targets. Clinically, staging suggests that the at-risk state or first episode is a period that requires particularly active and broad-based treatment, consistent with the hope that the temporal trajectory of the illness can be altered. Prompt treatment may be potentially neuroprotective and attenuate the neurostructural and neurocognitive changes that emerge with chronicity. Staging highlights the need for interventions at a service delivery level and implementing treatments at the earliest stage of illness possible.

Persistence of cognitive impairment and its negative impact on psychosocial functioning in lithium-treated, euthymic bipolar patients: a 6-year follow-up study.

BACKGROUND: Previous cross-sectional studies report that cognitive impairment is associated with poor psychosocial functioning in euthymic bipolar patients. There is a lack of long-term studies to determine the course of cognitive impairment and its impact on functional outcome. Method A total of 54 subjects were assessed at baseline and 6 years later; 28 had DSM-IV TR bipolar I or II disorder (recruited, at baseline, from a Lithium Clinic Program) and 26 were healthy matched controls. They were all assessed with a cognitive battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory) twice over a 6-year follow-up period. All patients were euthymic (Hamilton Rating Scale for Depression score lower than 8 and Young mania rating scale score lower than 6) for at least 3 months before both evaluations. At the end of follow-up, psychosocial functioning was also evaluated by means of the Functioning Assessment Short Test. RESULTS: Repeated-measures multivariate analysis of covariance showed that there were main effects of group in the executive domain, in the inhibition domain, in the processing speed domain, and in the verbal memory domain (p<0.04). Among the clinical factors, only longer illness duration was significantly related to slow processing (p=0.01), whereas strong relationships were observed between impoverished cognition along time and poorer psychosocial functioning (p<0.05). CONCLUSIONS: Executive functioning, inhibition, processing speed and verbal memory were impaired in euthymic bipolar out-patients. Although cognitive deficits remained stable on average throughout the follow-up, they had enduring negative effects on psychosocial adaptation of patients.

Quality of web-based information on bipolar disorder

OBJECTIVE: To evaluate web-based information on bipolar disorder and to assess particular content quality indicators. METHODS: Two keywords, "bipolar disorder" and "manic depressive illness" were entered into popular World Wide Web search engines. Websites were assessed with a standardized proforma designed to rate sites on the basis of accountability, presentation, interactivity, readability and content quality. "Health on the Net" (HON) quality label, and DISCERN scale scores were used to verify their efficiency as quality indicators. RESULTS: Of the 80 websites identified, 34 were included. Based on outcome measures, the content quality of the sites turned-out to be good. Content quality of web sites dealing with bipolar disorder is significantly explained by readability, accountability and interactivity as well as a global score. CONCLUSIONS: The overall content quality of the studied bipolar disorder websites is good.

Specificities of defense mechanisms in bipolar affective disorder: relations with symptoms and therapeutic alliance.

Defense mechanisms as a central notion of psychoanalysis have inspired various levels of interest in research in psychotherapy and psychopathology. Defense specificities have only recently been investigated systematically with regard to several clinical diagnoses, such as affective and personality disorders. For the present study, 30 inpatients diagnosed with Bipolar Affective Disorder I (BD) were interviewed. An observer-rater method, the Defense Mechanisms Rating Scales (DMRS), applied to session-transcripts, of assessment of defenses was used. A matched, nonclinical control group was introduced. Defense specificities in BD encompass a set of 5 immature defenses, of which omnipotence is linked with symptom level. The level of the therapeutic alliance is predicted by mature defenses. These results are discussed with regard to the psychological vulnerability of BD, and treatment implications for psychodynamic psychotherapy with such challenging patients are evoked.

Resultados preliminares de una escala experimental para la evaluación del trastorno antisocial de la personalidad según los criterios diagnósticos DSM-III

El estudio que se presenta consiste en la aplicación de una escala ajustada a criterios para el diagnóstico del Trantorno Antisocial de la Personalidad (eje II, 301.70) a una población penitenciaria a efecto de comprovar su valor discriminativo resto al diagnóstico clínico. La escala propuesta se reveló altamente sensible (87,5%), específica (90%) y predictiva (valor predictivo positivo del 89% y valor predectivo negativo del 87%) frente a la evaluación clínica. La evaluación se llevó a cabo por dos clínicos especializados mediante la utilización de una entrevista semiestructurada extraida y adaptada del DIS (Robins, 1981), obteniéndose un índice concordancia intragrupo entre evaluadores de 8.82. Se hacen refencias a la posible explicación de los falsos positivos obtenidos en la escala TAP.

Evaluación clínica y psicométrica del Trastorno Antisocial de la Personalidad

Este trabajo se diseñó para evaluar el Trastorno Antisocial de la Personalidad del DSM-III en presos, mediante una entrevista semiestructurada y una escala auto-informada, construida a partir de los criterios del trastorno. El elevado coeficiente de acuerdo interevaluadores (0,80) muestra que los criterios son muy fiables y operativos a efectos del diagnóstico. La escala auto-informada es aceptablemente sensible (88,23%) y específica (89,06%) respecto al trastorno antisocial de la personalidad. La consistencia interna alfa también se reveló muy elevada (0,92) y la escala tiene un alto valor discriminante frente a variables sociodemográficas y de índole penitenciaria.

Escalas empíricas derivadas de la escala de Desviación Psicopática del MMPI, para la evaluación del trastorno antisocial de la personalidad del DSM-III en delincuentes y no delincuentes

Se realiza un análisis de los ítems de la escala de Desviación Psicopática (Pd;50 ítems) del MMPI que más discriminan entre delincuentes diagnosticados del trastorno antisocial de la personalidad (DSM-III), de delincuentes que no tienen el trastorno y estudiantes, del que se resulta dos escalas (Pd-P;24 ítems y Pd-N;33 ítems). Estas escalas obtienen mayor sensibilidad y especificidad que la propia escala Pd respecto al trastorno. Psicométricamente tienen mayor validez y fiabilidad, propiedades, que junto a su brevedad, hacen aconsejable su uso en el estudio de la personalidad antisocial.

Eficacia de la terapia y/o los ejercicios terapéuticos en pacientes con trastorno temporomandibular. Alteración cóndilo-discal posterior.

Pregunta: ¿Qué tipo de terapia manual y/o ejercicios terapéuticos son más eficaces en pacientes con trastorno temporomandibular? Objetivo: Evaluar y comparar la eficacia de la terapia manual y/o los ejercicios terapéuticos en pacientes con trastorno temporomandibular. Metodología: la presente revisión bibliográfica se centra en bases de datos Medline, Scopus, PEDro y Google Scholar. Los artículos obtenidos fueron publicados entre los años 2004 y 2014. Se incluyen un total de 12 ensayos clínicos aleatorios. La literatura consta de pacientes con trastorno temporomandibular que hayan sido intervenidos con técnicas de terapia manual y/o ejercicios terapéuticos aplicados por un fisioterapeuta. Resultados: fueron seleccionados 10 estudios de alta evidencia científica para demostrar que la terapia manual combinada con ejercicio terapéutico disminuye el dolor, aumenta la abertura de la boca y corrige la anteversión de la cabeza. Conclusiones: la terapia manual combinada con ejercicios terapéuticos es efectiva para disminuir los síntomas en pacientes con trastornos temporomandibulares.

Factors modifying drug and placebo responses in randomized trials for bipolar mania

Factors modifying drug and placebo responses in randomized trials for bipolar mania. Yildiz A, Vieta E, Tohen M, Baldessarini RJ. Source Department of Psychiatry, Dokuz Eylül University, Izmir, Turkey. agul_yildiz@hotmail.com Abstract Randomized placebo-controlled trials (RCTs) are standard for assessing efficacy and safety of treatments. We pursued preliminary indications that some factors are associated differentially with responses to placebo or drugs in RCTs for bipolar mania. We meta-analysed data from RCTs to assess influences of study-site count, subjects' age, sex distribution, diagnostic subgroups, clinical features, trial-completion rates, and publication year on mean difference (MD) in mania ratings between intake and final assessments. In 38 RCTs involving 3812 placebo-treated and 6988 drug-treated patients, symptomatic improvement was similar in placebo arms of trials of effective (6.77, 95% CI 5.77-7.76) and ineffective (7.61, 95% CI 5.47-8.75) drugs. Lesser placebo responses (MD) and greater drug-placebo differences (Hedges' g) were associated with fewer study sites, younger patients' age, and male sex. More patients with initial psychotic features and more trial completion in drug arms were associated with greater drug-associated improvement (MD) and drug-placebo contrast (Hedges' g), whereas more mixed-state diagnoses decreased both measures. Identifying modifying factors can support more efficient and cost-effective designs of therapeutic trials. In trials for mania, fewer sites may limit placebo response and enhance drug-placebo contrasts.