Psychosocial interventions in bipolar disorder: a review.

INTRODUCTION: Multiple psychosocial interventions for bipolar disorder have been proposed in recent years. Therefore, we consider that a critical review of empirically validated models would be useful. METHODS: A review of the literature was conducted in Medline/PubMed for articles published during 2000-2010 that respond to the combination of "bipolar disorder" with the following key words: "psychosocial intervention", "psychoeducational intervention" and "psychotherapy". RESULTS: Cognitive-behavioral, psychoeducational, systematic care models, interpersonal and family therapy interventions were found to be empirically validated. All of them reported significant improvements in therapeutic adherence and in the patients' functionality. CONCLUSIONS: Although there are currently several validated psychosocial interventions for treating bipolar disorder, their efficacy needs to be specified in relation to more precise variables such as clinical type, comorbid disorders, stages or duration of the disease. Taking into account these clinical features would enable a proper selection of the most adequate intervention according to the patient's specific characteristics.

Intervenciones psicosociales en el Trastorno Bipolar: una revisión / Psychosocial interventions in Bipolar Disorder: A review

Introducción. En los últimos años han sido propuestas múltiples intervenciones psicosociales para el tratamiento del trastorno bipolar. Una revisión crítica de los modelos validados empíricamente resultaría de utilidad. Método. Se realizó una revisión bibliográfica de artículos publicados en Medline/Pub Med durante los años 2000-2010 que respondieran al cruce de trastorno bipolar con las siguientes palabras claves: "psychosocial intervention","psychoeducational intervention" y "psychotherapy". Resultados. Cuentan con validez empírica intervenciones provenientes de los modelos cognitivo-conductual, psicoeducativo, cuidado sistemático, interpersonal y familiar. Todas ellas dan cuenta de mejoras significativas en la adhesión a las indicaciones terapéuticas y un incremento en la funcionalidad Conclusiones. Si bien se utilizan diversas intervenciones psicosociales validadas para el abordaje del trastorno bipolar, su nivel de eficacia debería precisarse en base a variables más específicas como ser las formas clínicas, tipo de comorbilidad ,fases o duración de la enfermedad. Estas delimitaciones permitirían seleccionar la intervención más adecuada según las características del paciente (AU)

Introduction. Multiple psychosocial interventions for bipolar disorder have been proposed in recent years. Therefore, we consider that a critical review of empirically validated models would be useful. Methods. A review of the literature was conducted in Medline/Pub Med for articles published during 2000-2010that respond to the combination of "bipolar disorder" with the following key words: "psychosocial intervention", "psychoeducational intervention" and "psychotherapy". Results. Cognitive-behavioral, psychoeducational, systematic care models, interpersonal and family therapy interventions were found to be empirically validated. All of them reported significant improvements in therapeutic adherence and in the patients’ functionality. Conclusions. Although there are currently several validated psychosocial interventions for treating bipolar disorder, their efficacy needs to be specified in relation to more precise variables such as clinical type, comorbid disorders, stages or duration of the disease. Taking into account these clinical features would enable a proper selection of the most adequate intervention according to the patient’s specific characteristics (AU)

Diferencias terapéuticas de los medicamentos para el tratamiento de los trastornos bipolares: siete años después / Therapeutic and Pharmacologic Differences between Medications Used in the Treatment of Bipolar Disorders: Seven-Year Update

En el 2004 fue publicada una revisión detallada sobre las características terapéuticas de los medicamentos utilizados en el tratamiento de los trastornos bipolares [Tamayo JM et al. Actas Esp Psiquiatr 2004; 32 (Supl. 1): 3-17]. En aquél momento se podía concluir que si bien los eutimizantes compartían algunos mecanismos de acción, eran a la vez sustancialmente diferentes respecto a sus propiedades terapéuticas en las diferentes fases de los trastornos bipolares llevando a proponer un cambio en su clasificación genérica como “estabilizadores del estado de ánimo” a una nueva incluyendo: antimaníacos, estabilizadores parciales del ánimo y eutimizantes. Desde entonces, han sido publicados varios estudios doble-ciego aleatorizados y meta-análisis, explorando la eficacia y tolerabilidad de estos medicamentos. Esta revisión actualizada pretende evaluar, a la luz de la nueva evidencia, la validez de la propuesta de clasificación publicada en ese entonces (AU)

A detailed review was published in 2004 on the therapeutic properties of the medications used in the treatment of bipolar disorders (Tamayo, JM et al. Actas Esp Psiquiatr 2004; 32 (Suppl. 1): 3-17). At the time it could be concluded that although mood stabilizers (euthymics) share some action mechanisms, they are also significantly different from each other with respect to their therapeutic properties in the various phases of bipolar disorders. This led to a proposed change in their generic classification as “mood stabilizers” to a new classification that includes: antimanic medications, partial mood stabilizers, and euthymics. Since then, several randomized, double-blind studies and meta-analyses that explore the effectiveness and tolerability of these medications have been published. This updated review aims to assess the validity of the proposed classification in the light of new evidence (AU)

[Therapeutic and pharmacologic differences between medications used in the treatment of bipolar disorders: seven-year update]. / Diferencias terapéuticas de losmedicamentos para el tratamientode los trastornos bipolares: siete añosdespués.

A detailed review was published in 2004 on the therapeutic properties of the medications used in the treatment of bipolar disorders (Tamayo, JM et al. Actas Esp Psiquiatr 2004;32(Supl. 1):3-17). At the time it could be concluded that although mood stabilizers (euthymics) share some action mechanisms, they are also significantly different from each other with respect to their therapeutic properties in the various phases of bipolar disorders. This led to a proposed change in their generic classification as "mood stabilizers" to a new classification that includes: antimanic medications, partial mood stabilizers, and euthymics. Since then, several randomized, double-blind studies and meta-analyses that explore the effectiveness and tolerability of these medications have been published. This updated review aims to assess the validity of the proposed classification in the light of new evidence.

Definición e impacto de las depresiones resistentes/refractarias al tratamiento / Definition and impact of treatment-resistant depression

Major depressive disorder (MDD) is characterized by high rates of medical morbidity, low productivity, low life expectancy, and high rates of suicide. Therefore, the treatment of depressed patients involves, among others, an early diagnosis and treatment of the disease. Although an increasing number of antidepressants to treat MDD are available, approximately half of the patients do not respond, and near of two-thirds do not achieve remission after a first treatment attempt. For this project, it was conducted a detailed review using several databases such as MEDLINE, PsycINFO, EMBASE, the Cochrane Library, and LILACS from 1949 to March 2011 crossing terms related to the diagnosis and impact of the DRT. Unfortunately, original publications on DRT in Latin America are scarce and the findings and conclusions of this review have been based almost entirely on Anglo-Saxon scientific evidence. In a similar manner as described by medical microbiology, a major depressive episode (MDE) can be considered refractory when it has not responded to an adequate treatment with an established therapy. What constitutes an inadequate treatment has been the subject of considerable debate, but most experts would probably say it is the failure to achieve remission. The rationale for this approach is that not achieving remission often results in changes in work performance, increased risk of recurrences, chronicity, suicide, and impaired social functioning. Before considering a patient as TRD, is necessary to confirm the diagnosis of unipolar MDD ruling out other psychiatric disorders such as bipolar disorder, or other non-psychiatric medical diseases. After clarifying the diagnosis, and in the absence of remission, the physician is confronted with a great diversity of definitions and clinical criteria suggested for DRT. This variety of diagnostic alternatives, rather than enrich the portfolio of treatment options for DRT, often leads to serious discrepancies that hinder the effective management of the DRT. Unfortunately, more than 50 years after the discovery of the first antidepressants and increased knowledge about the neurobiological mechanisms of MDD and their interactions with the environment, for now there are no uniform guidelines on the definition and treatment of patients with DRT. Perhaps, the most accepted definition of DRT in the literature is that in which an inadequate response after one or two courses of antidepressant treatment with dose optimization, appropriate time of administration (usually between 8 and 12 weeks) and high level of adherence and compliance can be assured. Among the models proposed for the diagnosis of the DRT, Thase and Rush developed a frequently used tool, although with a predictive value, regarding the outcome of treatment, not systematically evaluated. It is based on five steps or levels that arbitrarily assume that the lack of remission after one single trial with an appropriate treatment is just enough to make a diagnosis of DRT. In addition, certain interventions such as tricyclic antidepressants or monoamine oxidase inhibitors are considered superior to first-line strategies available today. This review also defines the differential diagnosis of DRT such as pseudo-resistance, chronic depression, bipolar depression and tachyphylaxis, and describes the costs and consequences of DRT with an inadequate intervention.

El trastorno depresivo mayor (TDM) se acompaña de altas tasas de morbilidad médica, baja productividad, disminución de la esperanza de vida, altas tasas de suicidio y ha sido considerado como la primera causa de discapacidad laboral en las Américas. Por ello, la atención al paciente deprimido implica, entre otras cosas, el diagnóstico oportuno y el tratamiento adecuado del padecimiento. Aunque un número creciente de agentes antidepresivos está disponible para tratar la depresión, aproximadamente la mitad de los pacientes no responden y hasta dos tercios no logran la remisión después del tratamiento de primera línea. Para este proyecto se llevó a cabo una revisión detallada utilizando varias bases de datos como MEDLINE, PsycINFO, EMBASE, the Cochrane Library y LILACS, desde 1949 hasta marzo 2011, cruzando términos por medio de un sistema de búsqueda predefinido que permitió incluir artículos relevantes en relación al diagnóstico e impacto de las DRT. Desafortunadamente, las publicaciones originales en América Latina sobre DRT son escasas y los resultados y conclusiones de esta revisión han debido basarse casi en su totalidad en la producción científica anglosajona. En forma análoga a lo descrito por la microbiología médica, un episodio depresivo mayor (EDM) puede ser considerado como resistente al tratamiento cuando no ha respondido a un tratamiento adecuado con una terapia establecida. Lo que constituye una respuesta inadecuada ha sido objeto de considerable debate, pero la mayoría de los expertos hoy en día probablemente dirían que es el fracaso en el logro de la remisión. La justificación de este enfoque es que no conseguir la remisión, a pesar del tratamiento sugerido, suele dar lugar a la presencia de síntomas depresivos residuales (como insomnio, fatiga, dolores y ansiedad), que se han asociado de manera consistente con un peor efecto antidepresivo, alteraciones en el rendimiento laboral y un mayor riesgo de recurrencias, cronicidad, suicidio y deterioro del funcionamiento social en comparación con los pacientes cuya depresión está totalmente en remisión. Cuando se inicia una terapia con antidepresivos, los clínicos deben mantener la prudencia terapéutica para no sobre-estimarla. Los pacientes deben saber que la mayoría de las personas no alcanzan la remisión con rapidez y que los síntomas residuales son comunes. Según la intensidad de los síntomas residuales y otros factores, como la comorbilidad y el número de ensayos antes del fracaso terapéutico, una estrategia tan simple como la continuación del tratamiento con antidepresivos por algunas semanas más puede ser suficiente para alcanzar la remisión. En muchos casos, sin embargo, puede ser necesario el cambio a otro antidepresivo, la adición de otros medicamentos o la combinación con otro antidepresivo. Un artículo publicado en este número de la revista describe en detalle las estrategias terapéuticas para pacientes con depresión refractaria/ resistente al tratamiento (DRT) (Tamayo et al., 2011). Antes de proceder a clasificar un paciente deprimido como refractario/resistente al tratamiento es necesario confirmar el diagnóstico de TDM unipolar, descartando otros trastornos psiquiátricos como el trastorno bipolar u otras enfermedades médicas no psiquiátricas. Luego de la aclaración diagnóstica, y ante la ausencia de remisión, el médico se ve enfrentado a una gran diversidad en las definiciones y criterios clínicos sugeridos para las DRT. Esta variedad de alternativas diagnósticas, antes que enriquecer el portafolio de opciones terapéuticas, suele llevar a serias discrepancias que entorpecen la eficacia de su manejo, especialmente en países como los latinoamericanos donde los consensos basados en las necesidades regionales son escasos. Desafortunadamente, a más de 50 años del descubrimiento de los primeros antidepresivos y de un mayor conocimiento sobre los mecanismos neurobiológicos del TDM y sus interacciones con el entorno, no existen por ahora directrices uniformes sobre la definición y tratamiento de los pacientes con DRT. En la última década se ha publicado un número creciente de estudios de intervención en pacientes con este diagnóstico pero sin criterios operacionales consensuados y con más de 10 definiciones dispares. Quizá la definición más utilizada en la literatura médica es la de una respuesta insuficiente posterior a uno o dos esquemas de tratamiento antidepresivo que ha sido optimizado en dosis, administrado por un tiempo adecuado (usualmente entre ocho y 12 semanas) y en el que se tiene un nivel de certeza elevado sobre la adherencia y cumplimiento del mismo por parte del paciente. Las dosis subterapéuticas de los antidepresivos han sido reconocidas como una de las principales causas de la falta de remisión al tratamiento. Con el transcurso del tiempo la recomendación de dosis adecuadas ha aumentado de 150 mg/día a 250-300 mg/día de imipramina o su equivalente. La mayoría de los estudios, o bien no proporcionan la dosis máxima que se necesita para describir un tratamiento previo como un fracaso o un éxito, o sólo se refieren a ellas de forma genérica con frases como <

Revisión de la literatura médica sobre el manejo de las depresiones resistentes/refractarias al tratamiento / Literature review on management of treatment-resistant depression

Major depressive disorder (MDD) is a prevalent and costly disease that is usually associated with high rates of disability. The target for the treatment of MDD is to achieve and maintain remission or complete control of depressive symptoms by the choice of an effective antidepressant. Sometimes, despite evidence based-treatment, it is possible that the patient does not have a favorable response. Although there is an increasing number of antidepressants available to treat depression, approximately half of the patients do not respond and two-thirds do not achieve remission after first-line treatment. In these cases we refer to treatment-resistant depression (TRD) as is defined in an article in this issue of Salud Mental. The TRD is one of the most complex conditions in psychiatry from the therapeutic point of view due to different definitions, algorithms, and response criteria, especially in Latin America where the procedures based on regional needs and consensus are scarce and not always based on evidence. It was conducted a systematic review using several databases such as MEDLINE, PsycINFO, EMBASE, the Cochrane Library and LILACS from 1949 to March 2011 crossing terms which allowed the inclusion of relevant articles in the management of the TRD. Unfortunately, the original publications in Latin America are often based on TRD case report, so the results and conclusions of this review have been based entirely on Anglo-Saxon scientific production. The therapeutic strategies used in the TRD are many, and include combinations of antidepressants or other psychotropic agents, in some cases addition of psychotherapy and, in extreme cases, neurostimulation techniques such as electroconvulsive therapy (ECT). The study Sequenced Treatment Alternatives to Relieve Depression (STAR-D) is the largest trial of treatment for MDD conducted in real practice settings, and the first to study remission as a measure of pre-defined primary outcome. It consists of four different stages of resistance. It is clear that there are diminishing remission rates as the number of treatment trials increases. The strategies include: antidepressant dose optimization, addition of medications like thyroid hormone, lithium, or nutritional supplements, a combination of antidepressants, and addition of second-generation antipsychotics (SGAs). Evidence suggests that remission rates can be from 25% to 50%, although with some differences among the drugs recommended. Evidence supports the use of SGAs for increasing the level of remission of new-generation antidepressants, although neither the profit nor the long-term benefits of this strategy have been well established. Neuro-modulation techniques include ECT, repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). ECT remains a first line option for the treatment of DRT with response rates ranging from 50% to 89%. Finally, the effectiveness of cognitive-behavioral therapy (CBT) in the management of the DRT could be a useful alternative when practiced in conjunction with any of the pharmacological strategies. However, further studies are needed to recommend it as first line treatment.

El trastorno depresivo mayor (TDM) es una enfermedad costosa y prevalente que suele asociarse con altas tasas de discapacidad funcional. La meta para el tratamiento del TDM es lograr y mantener la remisión o el control completo de los síntomas depresivos por medio de la elección de un antidepresivo efectivo. Entre los factores a considerar para el logro de la remisión en pacientes deprimidos con los diferentes tratamientos disponibles, se incluyen su mecanismo de acción, el nivel de tolerabilidad, su facilidad de uso, su costo (directo e indirecto), la historia del tratamiento del paciente y su familia y algunas peculiaridades culturales que influyen en la adhesión al tratamiento y en la patoplastia clínica. En ocasiones, a pesar de un tratamiento ceñido a la evidencia, cabe la posibilidad de que el paciente no tenga una respuesta favorable al mismo. Aunque un número creciente de agentes antidepresivos está disponible para tratar la depresión, aproximadamente la mitad de los pacientes no responden y hasta dos tercios no logran la remisión después del tratamiento de primera línea. En estos casos nos referimos a la depresión refractaria/ resistente al tratamiento (DRT) tal como es definida en un artículo publicado en este número de la revista (Tamayo JM et al., 2011). La DRT es una de las condiciones más complejas en psiquiatría desde el punto de vista terapéutico debido a diferentes definiciones, algoritmos y criterios de respuesta que hacen difícil ofrecer alternativas eficaces, especialmente en América Latina donde los procedimientos basados en las necesidades regionales o el consenso son escasos y no siempre basados en la evidencia. Para este proyecto se llevó a cabo una revisión sistematizada utilizando varias bases de datos como MEDLINE, PsycINFO, EMBASE, the Cochrane Library y LILACS desde 1949 hasta marzo de 2011, cruzando términos por medio de un sistema de búsqueda predefinido que permitió incluir artículos relevantes en relación al manejo de las DRT. Desafortunadamente, las publicaciones originales en América Latina sobre la DRT suelen basarse en el reporte de casos por lo que los resultados y conclusiones de esta revisión han debido basarse en su totalidad en la producción científica anglosajona. Las estrategias terapéuticas utilizadas para la DRT son múltiples e incluyen combinaciones entre antidepresivos o con otros agentes psicotrópicos, en algunos casos adición de psicoterapia y en casos extremos técnicas de neuroestimulación como la TEC. El Estudio Secuenciado de Alternativas de Tratamiento para Aliviar la Depresión (STAR-D, por sus siglas en inglés) es el mayor ensayo de tratamiento del TDM llevado a cabo en entornos de práctica real, y el primero en estudiar la remisión como una medida de resultado primaria y predefinida. Está conformado por cuatro etapas diferentes de resistencia/refractariedad. Queda claro que hay rendimientos decrecientes a medida que el número de intentos de tratamiento aumenta. Pero cuando los pacientes siguen en tratamiento durante las cuatro fases que componen el STAR-D, aproximadamente el 67% alcanza la remisión. Las estrategias psicofarmacológicas incluyen cambio de antidepresivo en respondedores parciales luego de optimización de dosis, adición de medicamentos no antidepresivos como hormona tiroidea, litio o suplementos nutricionales, combinación de antidepresivos y adición de antipsicóticos de segunda generación (ASG). En general, se puede afirmar que los diversos estudios tienden a corroborar un incremento de las tasas de mejorías y remisiones después de seguir alguna de las estrategias terapéuticas mencionadas. Sin embargo, ningún estudio ha evaluado adecuadamente a los pacientes que no han respondido a múltiples cursos y combinaciones de terapias de medicamentos. En particular, respecto a las terapias de aumento, la evidencia sugiere que se pueden lograr tasas de remisión entre 25% y 50%, aunque con algunas diferencias entre los medicamentos recomendados. El uso del litio y de la hormona tiroidea, por ejemplo, si bien se basa en niveles de evidencia aceptables, se apoya en estudios pequeños, con diseños objetables y en pacientes menos refractarios que los que suelen incluirse en los estudios actuales. De todas las estrategias farmacológicas para aumentar la respuesta a los antidepresivos de nueva generación, la evidencia apoya con más frecuencia el uso de los ASG, aunque ni la rentabilidad ni el beneficio a largo plazo de esta estrategia han sido bien establecidos. Las técnicas de neuromodulación incluyen la TEC, la estimulación magnética transcraneana repetitiva (EMTr), la estimulación cerebral profunda (ECP) y la terapia de estimulación del nervio vago (ENV). La TEC sigue siendo una opción de primera línea para el tratamiento de la DRT con tasas de respuesta que van desde el 50% al 89%. Desafortunadamente, las estrategias de neuroestimulación, si bien suelen ser eficaces, especialmente la TEC y la ECP, son invasivas, costosas y deben relegarse como segunda línea de tratamiento en pacientes que no responden a las estrategias farmacológicas para la DRT. Finalmente, la eficacia de la terapia cognitivo-comportamental (TCC) en el manejo de las DRT podría ser una alternativa útil cuando se practica conjuntamente con alguna de las estrategias farmacológicas. Sin embargo, la eficacia de la psicoterapia en pacientes con DRT no ha sido fehacientemente demostrada y se requieren más estudios para recomendarla como primera línea de tratamiento. En cuanto al manejo a largo plazo de pacientes con DRT, el estudio STAR-D muestra que las tasas de remisión, cercanas al 67% luego de varias estrategias, se reducen al 45% cuando se incluyen en el análisis los pacientes que abandonan el estudio. Esto sugiere que el orden de administración de las alternativas terapéuticas aconsejadas hasta hoy necesita ser revaluado. Se requiere, pues, encontrar un tratamiento más rápido y más eficaz en el logro de la remisión en pacientes con TDM y estudios preliminares propenden por el uso temprano de la combinación de antidepresivos desde el inicio en pacientes con depresiones graves y caractersticas que sugieran un alto riesgo de resistencia/refractariedad.

Relationship between African-American or Caucasian origin and outcomes in the olanzapine treatment of acute mania: a pooled analysis of three adult studies conducted in the United States of America.

The aim of this study was to explore the role of ethnic origin in the treatment of acute bipolar mania. Treatment outcomes were studied in a post-hoc analysis of African-American (AA, n=41) and Caucasian (CA, n=190) adults treated with olanzapine in three studies conducted in the United States of America. Baseline demographics were similar except that the AA cohort had fewer women compared with the CA cohort (37 vs. 58%; P=0.01). Daily mean modal olanzapine dose and study discontinuation rate for AA and CA were: 16.2 mg vs. 16.6 mg and 41.5 vs. 25.3% (P=0.03), respectively. There were four (23.5% of discontinuers) and 19 (39.6% of discontinuers, P=0.14) discontinuations because of a poor response in the AA and CA groups, respectively. Drug exposure for the AA cohort was 18.7 days and that of the CA cohort was 19.3 days. Both cohorts showed similar symptom improvements, and safety outcomes were not statistically significantly different except for the following treatment-emergent adverse event frequencies for AA and CA cohorts, respectively: agitation (24.4 vs. 10.5%, P=0.04); dysmenorrhoea (20.0 vs. 3.6%, P=0.04); and dizziness postural (7.3 vs. 1.1%, P=0.04). Although study findings [limited by a smaller (18% of total population) AA cohort] need replication, they suggest that while many outcomes were similar in both cohorts, clinicians could benefit from the awareness of factors in the AA population that possibly influence study discontinuation rates, treatment-emergent adverse event reporting, and participation by sex.

Level of response and safety of pharmacological monotherapy in the treatment of acute bipolar I disorder phases: a systematic review and meta-analysis.

In recent years, combinations of pharmacological treatments have become common for the treatment of bipolar disorder type I (BP I); however, this practice is usually not evidence-based and rarely considers monotherapy drug regimen (MDR) as an option in the treatment of acute phases of BP I. Therefore, we evaluated comparative data of commonly prescribed MDRs for both manic and depressive phases of BP I. Medline, PsycINFO, EMBASE, the Cochrane Library, the ClinicalStudyResults.org and other data sources were searched from 1949 to March 2009 for placebo and active controlled randomized clinical trials (RCTs). Risk ratios (RRs) for response, remission, and discontinuation rates due to adverse events (AEs), lack of efficacy, or discontinuation due to any cause, and the number needed to treat or harm (NNT or NNH) were calculated for each medication individually and for all evaluable trials combined. The authors included 31 RCTs in the analyses comparing a MDR with placebo or with active treatment for acute mania, and 9 RCTs comparing a MDR with placebo or with active treatment for bipolar depression. According to the collected evidence, most of the MDRs when compared to placebo showed significant response and remission rates in acute mania. In the case of bipolar depression only quetiapine and, to a lesser extent, olanzapine showed efficacy as MDR. Overall, MDRs were well tolerated with low discontinuation rates due to any cause or AE, although AE profiles differed among treatments. We concluded that most MDRs were efficacious and safe in the treatment of manic episodes, but very few MDRs have demonstrated being efficacious for bipolar depressive episodes.

Effectiveness and safety of the combination of fluoxetine and olanzapine in outpatients with bipolar depression: an open-label, randomized, flexible-dose study in Puerto Rico.

We studied the effectiveness of olanzapine/fluoxetine combination (OFC) treatment of bipolar depressive episode (7 weeks, study period 1 [SP1]). Study period 1 responders (mean modal daily OFC dosage, 10.8/27.8 mg) were randomized to OFC continuation treatment or olanzapine (OLZ) monotherapy starting at 10 mg (12 weeks, SP2). Seventy-three percent of the 114 patients who entered into SP2 completed the trial. The Montgomery-Asberg Depression Rating Scale total score changes from baseline in SP1 (primary outcome) were significant (-20 +/- 10, P < 0.001) and, during SP2, worsened for patients in the OLZ group (OFC vs OLZ, -0.4 +/- 7.55 vs +8.2 +/- 14.1, respectively; P < 0.001). During SP1, 69% responded and 59% remitted. During SP2, significantly more patients in the OFC group maintained response (31.3% vs 12.5%) and remission (71.4% vs 39.6%) than patients in the OLZ group. Treatment-emergent adverse events with OFC (SP1 and SP2) included increased appetite, increased weight, somnolence, anxiety, insomnia, and depressed mood. Since visit 1, the mean weight increases (in pounds) were 4.8 +/- 6.8 for SP1 (P < 0.001) and 6.3 +/- 10.3 (OFC) or 10.7 +/- 11.3 (OLZ) for SP2; 50% (OLZ) and 33% (OFC) of the patients had a 7% or higher weight increase. For cholesterol, triglycerides, and low-density lipoprotein levels and some hepatic enzymes, there were statistically and clinically significant changes in both study periods but no differences between the SP2 groups. Study limitations included the open-label design and exclusion of the SP1 nonresponders from SP2. These study results suggest that improvements resulting from 7 weeks of acute OFC treatment of a bipolar depressive episode are maintained in responders for an additional 12 weeks with OFC, but switching to OLZ alone may result in symptom worsening.

Effects of open-label atomoxetine on African-American and Caucasian pediatric outpatients with attention-deficit/hyperactivity disorder.

BACKGROUND: Data on the management of attention-deficit/hyperactivity disorder (ADHD) in African-American children and adolescents are limited. METHODS: This study sought to evaluate the tolerability, safety, and efficacy of atomoxetine hydrochloride in the management of ADHD in African-American children and adolescents by conducting a post hoc subgroup analysis of 2 multicenter, open-label studies. RESULTS: Atomoxetine was safe and well tolerated, with >or=3.0% of African-Americans and Caucasians discontinuing treatment because of adverse events. A significantly higher proportion of Caucasians reported >or=1 treatment-emergent adverse event, including vomiting (7.2% vs 1.2%; P=.037) and fatigue (6.1% vs 0%; P=.012). No serious safety concerns were observed. Changes from baseline in height, weight, and hemodynamic variables were modest and similar in both racial subgroups. African-Americans and Caucasians showed significant improvement from baseline to end point in the mean ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-P:I). Scores decreased by 20.1 in African-Americans and by 19.55 in Caucasians, without significant between-group differences. Patients in both racial groups experienced similar, significant improvements in ADHDRS-IV-P:I inattention and hyperactivity-impulsivity symptoms, Clinical Global Impression-ADHD-Severity, and Conners' Parent Rating Scale-Revised: Short Form. CONCLUSIONS: Atomoxetine exhibited similar tolerability, safety, and efficacy profiles in African-Americans and Caucasians with ADHD.

Latino versus Caucasian response to atomoxetine in attention-deficit/hyperactivity disorder.

ABSTRACT We examined the effects of atomoxetine in Latino (n = 108) versus Caucasian (n = 1090) pediatric outpatients (aged 6 to <18 years) during the first 10-11 weeks of treatment in two multicenter, open-label trials. Mean modal doses were not significantly different in Latinos (1.22 mg/kg per day) versus Caucasians (1.27 mg/kg per day; p = 0.22). Both groups showed significant and similar improvements: Mean ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-P:I) scores decreased by 54% in Latinos (40.9-18.9; p < 0.001) and by 52% in Caucasians (37.7-18.2; p < 0.001). Other efficacy measures, such as Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S) and Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S), demonstrated similar and significant decreases. The only significant between-group difference was a greater decrease in the ADHDRS-IV-P:I Hyperactive/Impulsive subscale at weeks 8-11 for Latinos; however, Latinos had higher baseline scores compared with Caucasians. This was not demonstrated in the CPRS-R:S Hyperactivity subscale. There was a significantly higher frequency of CYP2D6 slow metabolizers in Caucasians compared with Latinos. Caucasians reported significantly more abdominal and throat pain, whereas Latinos reported more decreased appetite and dizziness, but no differences in other common adverse events were reported. No suicidal behavior was reported in either group. We found that Latino and Caucasian children with attention-deficit/hyperactivity disorder (ADHD) exhibit a similar pattern of efficacy and tolerability with atomoxetine. The lack of placebo controls was a limitation of this study.

[The importance of detection and treatment of somatic symptoms in Latin American patients with major depression]. / La importancia de la detección y el tratamiento de los síntomas somáticos en pacientes latinoamericanos con depresión mayor.

OBJECTIVE: Major depression is a disease characterized by the presence of mental and somatic symptoms, the latter affecting considerably the diagnostic and therapeutic procedures and the prognosis. METHOD: We searched for published articles until June 2006 crossing several terms which allow us to include those articles referring to the comorbidity of major depression and somatic symptoms, the prevalence of that comorbidity in Latino Americans, and/or the impact and patterns of use of the antidepressant treatments in patients with major depression and associated somatic symptoms. RESULTS: Somatic symptoms in Latino Americans with major depression are common, probably more than in other populations around the world. They compromise the response to treatment, are associated with refractoriness and chronicity, and are usually denied in the psychiatry practice in some Latin American countries, where the practice in prescribing low doses of antidepressants is common and could affect the control of residual somatic symptoms with higher rates of recurrences. CONCLUSION: Clinicians working in Latin American countries must be prepared to detect somatic symptoms in their patients with major depression, looking for the prescription of appropriate therapeutic doses of the antidepressants.

La importancia de la detección y el tratamiento de los síntomas somáticos en pacientes latinoamericanos con depresión mayor / The importance of detection and treatment of somatic symptoms in Latin American patients with major depression

OBJETIVO: La depresión mayor es una enfermedad caracterizada por la presencia tanto de síntomas mentales como somáticos, los cuales afectan en forma significativa los procesos diagnósticos y terapéuticos así como el pronóstico. MÉTODO: Usamos una búsqueda de artículos publicados hasta Junio 2006 cruzando términos que nos permitieran incluir artículos que hiciesen referencia a la comorbilidad entre depresión mayor y síntomas somáticos, a la prevalencia de dicha comorbilidad en Latinoamericanos y/o al impacto y el patrón de uso de antidepresivos en pacientes con depresión mayor y síntomas somáticos asociados. RESULTADOS: Los síntomas somáticos en Latinoamericanos con depresión mayor son frecuentes, probablemente más que en otras poblaciones, afectan significativamente la respuesta al tratamiento, se asocian a mayor refractariedad y cronicidad y no siempre son tenidos en cuenta en la práctica psiquiátrica de algunos países Latinoamericanos, donde la práctica usual de prescribir dosis bajas de antidepresivos podría comprometer el control de los síntomas somáticos residuales y asociarse a mayores tasas de recurrencias. CONCLUSION: Los clínicos que laboran en Latinoamérica deben ser acuciosos en la detección de los síntomas somáticos de sus pacientes con depresión mayor y siempre procurar la prescripción de dosis terapéuticas del antidepresivo de su selección.

OBJECTIVE: Major depression is a disease characterized by the presence of mental and somatic symptoms, the latter affecting considerably the diagnostic and therapeutic procedures and the prognosis. METHOD: We searched for published articles until June 2006 crossing several terms which allow us to include those articles referring to the comorbidity of major depression and somatic symptoms, the prevalence of that comorbidity in Latino Americans, and/or the impact and patterns of use of the antidepressant treatments in patients with major depression and associated somatic symptoms. RESULTS: Somatic symptoms in Latino Americans with major depression are common, probably more than in other populations around the world. They compromise the response to treatment, are associated with refractoriness and chronicity, and are usually denied in the psychiatry practice in some Latin American countries, where the practice in prescribing low doses of antidepressants is common and could affect the control of residual somatic symptoms with higher rates of recurrences. CONCLUSION: Clinicians working in Latin American countries must be prepared to detect somatic symptoms in their patients with major depression, looking for the prescription of appropriate therapeutic doses of the antidepressants.

Outcomes for Latin American versus White patients suffering from acute mania in a randomized, double-blind trial comparing olanzapine and haloperidol.

Data from a published double-blind randomized trial comparing olanzapine versus haloperidol in acute mania were used to address the response and tolerability of Latin American patients. Primary efficacy end point was the remission rate (Young Mania Rating Scale score

The level of recognition of physical symptoms in patients with a major depression episode in the outpatient psychiatric practice in Puerto Rico: an observational study.

BACKGROUND: This study was designed to evaluate the psychiatrists' level of recognition of somatic symptoms associated to a major depressive episode (MDE) (DSM-IV-TR criteria) and the impact of those somatic symptoms on the treatment effectiveness. METHODS: This non-interventional study was conducted in 25 medical offices in Puerto Rico from February to December 2003. It had 2 visits separated by 8 weeks. The level of recognition was determined by: the correlation between the physician clinical evaluation and their patients' self-evaluations through different validated instruments using kappa statistics. Chi-square test was used to evaluate the impact of somatic symptoms on treatment antidepressants' effectiveness. RESULTS: All the 145 recruited patients reported the presence of at least one somatic symptom associated with their current MDE. In the two visits covered by the study, a fair agreement between the psychiatrists' and the patients' reports was noted for headache, abdominal pain and upper limb pains (0.4003 or= 0.6594). For other painful symptoms and painless somatic symptoms, the Kappa values obtained were non-significant. Slight but significant reductions in depression and painful symptoms severity were observed after 8 weeks of treatment. A proportional relationship between the pain and depression severity was observed (p < 0.0001). CONCLUSION: The study results show that somatic symptoms: are very common in depressed Puerto Rican patients; are significant under-reported by psychiatrists; and have a significant impact on the antidepressant effectiveness.

Bases biológicas de la dependencia de las drogas. Hacia un enfoque integral del problema / Biologic bases of drug dependence: towards an integral approach of the problem

El abuso y la dependencia de las drogas son problemas complejos y costosos que requieren una intervención terapéutica polimodal e integral. En los últimos años se han dado varios descubrimientos científicos relacionados con las bases biológicas de estos trastornos. Ello ha permitido desarrollar programas que incluyen el uso de diferentes psicofármacos y técnicas psicoterapéuticas que posibilitan una modulación de las vías neuronales disfuncionales. La investigación del sistema mesolímbico dopaminérgico y de los receptores opioides del tallo cerebral y del núcleo accumbens sumada al develamiento de los diferentes mecanismos intraneuronales, han permitido comprender mejor los cambios cerebrales y comportamentales debidos al consumo agudo y crónico de drogas. Tales hallazgos biológicos son el propósito de esta revisión basada en una búsqueda de artículos a través de MEDLINE

Drugs abuse and dependence are complex and expensive disorders that require a polymodal and integral therapeutic intervention. Several scientific discoveries related to the biological bases of these disorders have recently arisen. These discoveries guide the design of programs that include different psychotropic drugs and psychotherapeutic technics that allow a modulation of the neuronal dysfunction process. Research on the mesolimbic dopaminergic system and the opioid receptors in the brain stem and the nucleus accumbens added to new knowledge of different intraneuronal mechanisms, allow a better understanding of cerebral and behavioral changes due to acute and chronic consumption of drugs. Such biological findings are the purpose of this revie based on a MEDLINE search of articles