Javier Ballesteros

Effectiveness of pindolol plus serotonin uptake inhibitors in depression: a meta-analysis of early and late outcomes from randomised controlled trials

BACKGROUND Contradictory results on the efficacy of pindolol associated with selective serotonin reuptake inhibitors (SSRIs) in depressive illness have been published and no former review has produced an overall figure of its efficacy. This study aims to review the efficacy and tolerability of pindolol plus SSRIs in depressive illness. METHODS A meta-analysis of randomised controlled trials (RCTs) comparing pindolol plus SSRIs with placebo plus SSRIs. RESULTS Nine RCTs met inclusion criteria. Outcome favoured pindolol at 2 weeks time (N=5; OR=2.8; 95% CI 1.4-5.7), but not at four to 6 weeks (N=7; OR=1.4; 95% CI 0.8-2.7). Results for early outcome studies were robust to sensitivity analysis. Nineteen more studies, averaging null results, would be needed to change the overall probability (P=0.0001) to a non-significant figure. CONCLUSIONS Pindolol seems to hasten the response to SSRIs in depression with a timing window circumscribed to the first weeks of treatment.

Principal components of mania

OBJECTIVE An alternative to the categorical classification of psychiatric diseases is the dimensional study of the signs and symptoms of psychiatric syndromes. To date, there have been few reports about the dimensions of mania, and the existence of a depressive dimension in mania remains controversial. The aim of this study was to investigate the dimensions of manic disorder by using classical scales to study the signs and symptoms of affective disorders. METHODS One-hundred and three consecutively admitted inpatients who met DSM IV criteria for bipolar disorder, manic or mixed were rated with the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HDRS-21). A principal components factor analysis of the HDRS-21 and the YMRS was carried out. RESULTS Factor analysis showed five independent and clinically interpretable factors corresponding to depression, dysphoria, hedonism, psychosis and activation. The distribution of factor scores on the depressive factor was bimodal, whereas it was unimodal on the dysphoric, hedonism and activation factors. Finally, the psychosis factor was not normally distributed. LIMITATIONS Patients of the sample were all medicated inpatients. CONCLUSIONS Mania seems to be composed of three core dimensions, i.e. hedonism, dysphoria and activation, and is frequently accompanied by a psychotic and a depressive factor. The existence of a depressive factor suggests that it is essential to evaluate depression during mania, and the distribution of the depressive factor supports the existence of two different states in mania.

Evaluación psicométrica comparativa de las versiones en español de 6, 17 y 21 ítems de la Escala de valoración de Hamilton para la evaluación de la depresión

Fundamento y objetivo Los estudios espanoles previos de la Hamilton Depression Rating Scale(HDRS) se han centrado en su version de 17 items y se han realizado fundamentalmente enpoblaciones hospitalizadas. En el presente estudio se ha llevado a cabo una evaluacion psicometricacomparativa de las versiones en espanol de la HDRS de 6, 17 y 21 items en pacientescon depresion en tratamiento ambulatorio. Pacientes y metodo Estudio multicentrico, observacional y prospectivo en pacientes con depresion,clinicamente estables o inestables. Se evaluaron la validez discriminante, la fiabilidad(consistencia interna, estabilidad temporal y entre observadores) y la sensibilidad al cambio dela HDRS con 6, 17 y 21 items. Resultados Se incluyo a 168 pacientes de 15 centros de asistencia psiquiatrica. Las versionesde 6, 17 y 21 items de la HDRS presentaron una adecuada validez discriminante (HDRS-ImpresionClinica Global de Gravedad, p Conclusiones Las versiones en espanol de la HDRS con 6, 17 y 21 items presentan similarespropiedades psicometricas. El buen rendimiento de HDRS-6 justifica su utilizacion en mediosambulatorios y en atencion primaria.

First episode in bipolar disorder: misdiagnosis and psychotic symptoms

BACKGROUND This study explores factors that can influence other psychotic diagnoses in the first episode of a DSM-III-R bipolar disorder. METHODS It includes all 163 bipolar in-patients and out-patients in the state of Alava, North of Spain (Basque country) from February 1994 to May 1996. Patients were divided into two non-overlapping groups: unstable diagnoses, bipolars with an initial diagnosis of schizophrenia (or other psychosis), and stable diagnoses of bipolar disorder. RESULTS A logistic regression analysis using marital status, age at onset and mood incongruent psychotic symptoms found that the latter was the only independent factor significantly associated with an unstable diagnosis.

Radiotherapy plus nimotuzumab or placebo in the treatment of high grade glioma patients: results from a randomized, double blind trial

BackgroundThe prognosis of patients bearing high grade glioma remains dismal. Epidermal Growth Factor Receptor (EGFR) is well validated as a primary contributor of glioma initiation and progression. Nimotuzumab is a humanized monoclonal antibody that recognizes the EGFR extracellular domain and reaches Central Nervous System tumors, in nonclinical and clinical setting. While it has similar activity when compared to other anti-EGFR antibodies, it does not induce skin toxicity or hypomagnesemia.MethodsA randomized, double blind, multicentric clinical trial was conducted in high grade glioma patients (41 anaplastic astrocytoma and 29 glioblastoma multiforme) that received radiotherapy plus nimotuzumab or placebo. Treatment and placebo groups were well-balanced for the most important prognostic variables. Patients received 6 weekly doses of 200 mg nimotuzumab or placebo together with irradiation as induction therapy. Maintenance treatment was given for 1 year with subsequent doses administered every 3 weeks. The objectives of this study were to assess the comparative overall survival, progression free survival, response rate, immunogenicity and safety.ResultsThe median cumulative dose was 3200 mg of nimotuzumab given over a median number of 16 doses. The combination of nimotuzumab and RT was well-tolerated. The most prevalent related adverse reactions included nausea, fever, tremors, anorexia and hepatic test alteration. No anti-idiotypic response was detected, confirming the antibody low immunogenicity. The mean and median survival time for subjects treated with nimotuzumab was 31.06 and 17.76 vs. 21.07 and 12.63 months for the control group.ConclusionsIn this randomized trial, nimotuzumab showed an excellent safety profile and significant survival benefit in combination with irradiation.Trial registrationCuban National Register for clinical trials (No. 1745) (http://registroclinico.sld.cu/ensayos).

Tardive dyskinesia associated with higher mortality in psychiatric patients: results of a meta-analysis of seven independent studies.

This article reports a meta-analysis of seven independent studies on the association of tardive dyskinesia with all-cause mortality in psychiatric patients. Most of the studies included provide either small sample sizes or follow-up periods too short to reach a substantive conclusion on their own. In the meta-analysis, the overall odds ratio (OR) was significant when calculated either by the fixed-effects model (OR = 1.4, 95% confidence interval [CI] = 1.2-1.7, p < 0.005) or the random-effects model (OR = 1.4, 95% CI = 1.1-1.8, p < 0.005). There was no overall heterogeneity (Q test = 8.1, df = 7,p = 0.32). The overall estimate changed within study designs (OR = 1.4,p = 0.002 in three prospective controlled studies; OR = 2.2, p = 0.02 in two prospective uncontrolled studies; and OR = 0.9, p = 0.80 in two retrospective controlled studies). It was modified upward when the two most influential studies (one prospective and one retrospective) were removed from the overview (OR = 2.2, 95% CI = 1.4-3.5,p = 0.001; Q test = 0.81, df = 4,p = 0.94). The conclusion of the meta-analysis was that tardive dyskinesia must be considered a weak risk factor in terms of mortality. It remains to be elucidated whether it is a risk factor on its own or just a surrogate for any unknown organic liability.

Systematic review of pharmacological treatments in fragile X syndrome

BackgroundFragile X syndrome (FXS) is considered the most common cause of inherited mental retardation. Affected people have mental impairment that can include Attention Deficit and/or Hyperactivity Disorder (ADHD), autism disorder, and speech and behavioural disorders. Several pharmacological interventions have been proposed to treat those impairments.MethodsSystematic review of the literature and summary of the evidence from clinical controlled trials that compared at least one pharmacological treatment with placebo or other treatment in individuals with diagnosis of FXS syndrome and assessed the efficacy and/or safety of the treatments. Studies were identified by a search of PubMed, EMBASE and the Cochrane Databases using the terms fragile X and treatment. Risk of bias of the studies was assessed by using the Cochrane Collaboration criteria.ResultsThe search identified 276 potential articles and 14 studies satisfied inclusion criteria. Of these, 10 studies on folic acid (9 with crossover design, only 1 of them with good methodological quality and low risk of bias) did not find in general significant improvements. A small sample size trial assessed dextroamphetamine and methylphenidate in patients with an additional diagnosis of ADHD and found some improvements in those taking methylphenidate, but the length of follow-up was too short. Two studies on L-acetylcarnitine, showed positive effects and no side effects in patients with an additional diagnosis of ADHD. Finally, one study on patients with an additional diagnosis of autism assessed ampakine compound CX516 and found no significant differences between treatment and placebo. Regarding safety, none of the studies that assessed that area found relevant side effects, but the number of patients included was too small to detect side effects with low incidence.ConclusionCurrently there is no robust evidence to support recommendations on pharmacological treatments in patients with FXS in general or in those with an additional diagnosis of ADHD or autism.

Outcome of memory rehabilitation in traumatic brain injury assessed by neuropsychological tests and questionnaires.

Objectives:To evaluate the effectiveness of a memory rehabilitation program. To compare different outcome measures. Participants:Twelve patients with severe traumatic brain injury. Setting:Outpatient rehabilitation service. Main outcome measures:Rey-Osterrieth Complex Figure Test (REY), California Verbal Learning Test (CVLT), Rivermead Behavioural Memory Test (RBMT), and the Memory Failures in Everyday Memory Questionnaire (MFE). Statistical analysis:Exact nonparametric procedures. Results:All patients achieved meaningful functional gains. Modest improvements were found in some of the scales of the CVLT but not in the REY, RBMT, or MFE. Conclusion:Functional gains did not correlate with improvement in memory processes. Measurement of changes in independence in activities of daily living mediated by compensatory aids and educational intervention plans with relatives are proposed.

The Effectiveness of Donepezil for Cognitive Rehabilitation After Traumatic Brain Injury: A Systematic Review

S STUDIES have shown the important role acetylcholine pathways and transmission play for improving cognitive functions after sustained injuries.1,2 These results opened the way to test the efficacy of acetylcholinesterase inhibitors (AChEIs), among other drugs, for cognitive rehabilitation after traumatic brain injury (TBI). Early studies reported encouraging findings on the efficacy of first-generation AChEIs such as physostigmine.3,4 Newer and safer AChEIs have since been developed for the treatment of Alzheimer’s disease. However, the evidence supporting the off-label use of AChEIs for the rehabilitation of cognitive impairments sustained after TBI is scarce. We systematically reviewed all the published evidence concerning the efficacy and safety of AChEIs for the rehabilitation of cognitive impairments after TBI. Preliminary searches on electronic databases indicated that donepezil was practically the

Number of prior episodes and the presence of depressive symptoms are associated with longer length of stay for patients with acute manic episodes

BackgroundFew studies have analyzed predictors of length of stay (LOS) in patients admitted due to acute bipolar manic episodes. The purpose of the present study was to estimate LOS and to determine the potential sociodemographic and clinical risk factors associated with a longer hospitalization. Such information could be useful to identify those patients at high risk for long LOS and to allocate them to special treatments, with the aim of optimizing their hospital management.MethodsThis was a cross-sectional study recruiting adult patients with a diagnosis of bipolar disorder (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) criteria) who had been hospitalized due to an acute manic episode with a Young Mania Rating Scale total score greater than 20. Bivariate correlational and multiple linear regression analyses were performed to identify independent predictors of LOS.ResultsA total of 235 patients from 44 centers were included in the study. The only factors that were significantly associated to LOS in the regression model were the number of previous episodes and the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at admission (P < 0.05).ConclusionsPatients with a high number of previous episodes and those with depressive symptoms during mania are more likely to stay longer in hospital. Patients with severe depressive symptoms may have a more severe or treatment-resistant course of the acute bipolar manic episode.