A Multicentre, Randomised, Controlled Trial of a Combined Clinical Treatment for First-Episode Psychosis.

INTRODUCTION: There is evidence that early intervention contributes to improving the prognosis and course of first-episode psychosis (FEP). However, further randomised treatment clinical trials are needed. OBJECTIVES: The aim of this study was to compare the efficacy of a combined clinical treatment involving Cognitive Behavioural Therapy (CBT) as an adjunctive to treatment-as-usual (TAU) (CBT+TAU) versus TAU alone for FEP. PATIENTS AND METHODS: In this multicentre, single-blind, randomised controlled trial, 177 participants were randomly allocated to either CBT+TAU or TAU. The primary outcome was post-treatment patient functioning. RESULTS: The CBT+TAU group showed a greater improvement in functioning, which was measured using the Global Assessment Functioning (GAF) and Functioning Assessment Short Test (FAST), compared to the TAU group post-treatment. The CBT+TAU participants exhibited a greater decline in depressive, negative, and general psychotic symptoms; a better awareness of the disease and treatment adherence; and a greater increase in brain-derived neurotrophic factor levels than TAU participants. CONCLUSIONS: Early intervention based on a combined clinical treatment involving CBT as an adjunctive to standard treatment may improve clinical and functional outcomes in FEP.

Comparing the phenomenology of depressive episodes in bipolar I and II disorder and major depressive disorder within bipolar disorder pedigrees.

OBJECTIVE: In a prior study of bipolar disorder pedigrees, we demonstrated distinct clinical differences between depressive episodes in bipolar disorder and major depressive disorder (MDD), including differentiation between these conditions using the Probabilistic Approach to Bipolar Depression. The aim of this retrospective study was to compare the phenomenology of the most severe lifetime depressive episodes between bipolar I (BP-I) and II (BP-II) disorder subtypes and MDD in these pedigrees. METHOD: Patients with DSM-IV diagnoses of BP-I (n = 202), BP-II (n = 44), and MDD (n = 120) from bipolar disorder pedigrees were assessed using the Diagnostic Interview for Genetic Studies between 1998 and 2012. Multivariate logistic regression was used to identify distinguishing clinical features. The utility of the Probabilistic Approach in distinguishing BP-I and BP-II depression from MDD was assessed. RESULTS: BP-I differed from MDD in terms of greater rates of psychomotor retardation (P < .05) and psychotic features (P < .05). BP-II was distinguished from MDD (P < .01) by the greater likelihood of mixed features. Patients with BP-II had a greater likelihood of mixed features (P < .001) and a lesser likelihood of psychomotor retardation (P < .05) compared to those with BP-I. The Probabilistic Approach significantly differentiated both BP-I and BP-II from MDD (P < .01 to P < .001, depending on cutoff) but did not robustly distinguish between BP-I and BP-II. CONCLUSIONS: First, the differentiation of BP-II from both BP-I depression and MDD in terms of the presence of mixed symptoms is of particular interest given the current debate over "mixed specifiers" for these conditions in DSM-5. Second, the Probabilistic Approach to Bipolar Depression was demonstrated for the first time to significantly distinguish both bipolar disorder subtypes from MDD.

Brain structural correlates of sensory phenomena in patients with obsessive-compulsive disorder.

BACKGROUND: Sensory phenomena (SP) are uncomfortable feelings, including bodily sensations, sense of inner tension, "just-right" perceptions, feelings of incompleteness, or "urge-only" phenomena, which have been described to precede, trigger or accompany repetitive behaviours in individuals with obsessive-compulsive disorder (OCD). Sensory phenomena are also observed in individuals with tic disorders, and previous research suggests that sensorimotor cortex abnormalities underpin the presence of SP in such patients. However, to our knowledge, no studies have assessed the neural correlates of SP in patients with OCD. METHODS: We assessed the presence of SP using the University of São Paulo Sensory Phenomena Scale in patients with OCD and healthy controls from specialized units in São Paulo, Brazil, and Barcelona, Spain. All participants underwent a structural magnetic resonance examination, and brain images were examined using DARTEL voxel-based morphometry. We evaluated grey matter volume differences between patients with and without SP and healthy controls within the sensorimotor and premotor cortices. RESULTS: We included 106 patients with OCD and 87 controls in our study. Patients with SP (67% of the sample) showed grey matter volume increases in the left sensorimotor cortex in comparison to patients without SP and bilateral sensorimotor cortex grey matter volume increases in comparison to controls. No differences were observed between patients without SP and controls. LIMITATIONS: Most patients were medicated. Participant recruitment and image acquisition were performed in 2 different centres. CONCLUSION: We have identified a structural correlate of SP in patients with OCD involving grey matter volume increases within the sensorimotor cortex; this finding is in agreement with those of tic disorder studies showing that abnormal activity and volume increases within this region are associated with the urges preceding tic onset.

Integrated treatment of first episode psychosis with online training (e-learning): study protocol for a randomised controlled trial.

BACKGROUND: The integrated treatment of first episode psychosis has been shown to improve functionality and negative symptoms in previous studies. In this paper, we describe a study of integrated treatment (individual psychoeducation complementary to pharmacotherapy) versus treatment as usual, comparing results at baseline with those at 6-month re-assessment (at the end of the study) for these patients, and online training of professionals to provide this complementary treatment, with the following objectives: 1) to compare the efficacy of individual psychoeducation as add-on treatment versus treatment as usual in improving psychotic and mood symptoms; 2) to compare adherence to medication, functioning, insight, social response, quality of life, and brain-derived neurotrophic factor, between both groups; and 3) to analyse the efficacy of online training of psychotherapists. METHODS/DESIGN: This is a single-blind randomised clinical trial including patients with first episode psychosis from hospitals across Spain, randomly assigned to either a control group with pharmacotherapy and regular sessions with their psychiatrist (treatment as usual) or an intervention group with integrated care including treatment as usual plus a psychoeducational intervention (14 sessions). Training for professionals involved at each participating centre was provided by the coordinating centre (University Hospital of Álava) through video conferences. Patients are evaluated with an extensive battery of tests assessing clinical and sociodemographic characteristics (Positive and Negative Syndrome Scale, State-Trait Anxiety Inventory, Liebowitz Social Anxiety Scale, Hamilton Rating Scale for Depression, Scale to Assess Unawareness of Mental Disorders, Strauss and Carpenter Prognostic Scale, Global Assessment of Functioning Scale, Morisky Green Adherence Scale, Functioning Assessment Short Test, World Health Organization Quality of Life instrument WHOQOL-BREF (an abbreviated version of the WHOQOL-100), and EuroQoL questionnaire), and brain-derived neurotrophic factor levels are measured in peripheral blood at baseline and at 6 months. The statistical analysis, including bivariate analysis, linear and logistic regression models, will be performed using SPSS. DISCUSSION: This is an innovative study that includes the assessment of an integrated intervention for patients with first episode psychosis provided by professionals who are trained online, potentially making it possible to offer the intervention to more patients. TRIAL REGISTRATION: NCT01783457 clinical trials.gov. Date of registration in primary registry 23 January 2013.

Do benzodiazepines moderate the effectiveness of bitemporal electroconvulsive therapy in major depression?

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for depression. However, the use of concomitant medications during ECT is controversial, especially benzodiazepines, as some past evidence suggests these may reduce the efficacy of ECT. This study analysed the effect of benzodiazepines on treatment outcomes in a group of depressed patients treated with bitemporal (BT) ECT. METHODS: 90 patients with major depression who received BT ECT were analysed. Clinical, demographic and ECT data were extracted from clinical records. Mood improvement was rated by trained psychiatrists using the Hamilton Depression Rating Scale (HDRS-21) at baseline and after the final ECT treatment. The association between benzodiazepine dose and mood outcomes over the ECT course was examined with regression analyses, controlling for variables that may affect ECT efficacy. RESULTS: Hierarchical multiple regression analysis found only current episode duration (t=-4.77, p<0.001) was a significant predictor of change in HDRS. Benzodiazepine dose was not associated with a change in HDRS (p>0.05, R(2)=0.39). LIMITATIONS: This was a retrospective study. The use of the half-age dosing method for ECT did not permit examination of the effects of benzodiazepines on seizure threshold. CONCLUSIONS: Benzodiazepines did not affect the efficacy of BT ECT with the dosing method used. However, these results may not generalise to other forms of ECT, ECT given with other methods of dose determination or to other populations less responsive to ECT.

Efficacy of functional remediation in bipolar disorder: a multicenter randomized controlled study.

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukey's post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.