Randomized clinical trial of integral cognitive remediation program for major depression (INCREM).

BACKGROUND: Despite achieving clinical remission, patients with depression encounter difficulties to return to their premorbid psychosocial functioning. Cognitive dysfunction has been proposed to be a primary mediator of functional impairment. Therefore, the new non-pharmacological procognitive strategy INtegral Cognitive REMediation for Depression (INCREM) has been developed with the aim of targeting cognitive and psychosocial functioning. METHODS: This is a single-blind randomized controlled clinical trial with three treatment arms. Fifty-two depressed patients in clinical remission, with psychosocial difficulties and cognitive impairment, were randomly assigned to receive INCREM intervention, Psychoeducation programme, or treatment as usual. Patients were assessed before and after the study period, and six months after. The primary outcome was the change from baseline of patients' psychosocial functioning. Changes in cognitive functioning and other variables were considered secondary outcomes. RESULTS: The analysis showed a significant improvement in psychosocial functioning in the INCREM group, especially six months after the intervention, compared to patients who received the psychoeducation programme. An improvement in cognitive performance was also observed in the INCREM group. LIMITATIONS: This study includes a small sample size due to the anticipated end of the clinical trial because of the COVID-19 pandemic. DISCUSSION: These results provide preliminary evidence on the feasibility and potential efficacy of the INCREM program to improve not only cognitive performance but also psychosocial functioning in clinically remitted depressed patients, and such improvement is maintained six months after. It can be speculated that the maintenance is mediated by the cognitive enhancement achieved with INCREM.

Brain metabolic changes in patients with treatment resistant schizophrenia treated with deep brain stimulation: A series of cases.

Deep brain stimulation (DBS) has been found to be effective in treatment resistant neurological and psychiatric disorders. So far there has been only one completed trial in schizophrenia, in which seven treatment resistant patients received DBS in the subgenual anterior cingulate cortex (sgACC, N = 4) or the nucleus accumbens (NAc, N = 3); four met symptomatic response criteria over the trial period. Six patients underwent 18 F-FDG PET at baseline and after at least 6 months of stimulation. Individual patient analysis indicated that DBS to both the sgACC and NAc was associated with local and distant changes in glucose metabolism. Increments and decrements of brain activity were observed in regions that included the medial prefrontal cortex, the dorsolateral prefrontal cortex, the anterior cingulate cortex, the caudate nucleus, the NAc, the hippocampus and the thalamus. Increased activity appeared to be associated with clinical improvement. These preliminary findings suggest that DBS acts by modulating cerebral activity in the cortico-basal-thalamic-cortical circuit in patients with schizophrenia who show improvement in psychotic symptoms.

A pharmacogenetic intervention for the improvement of the safety profile of antipsychotic treatments.

Antipsychotic drugs fail to achieve adequate response in 30-50% of treated patients and about 50% of them develop severe and lasting side effects. Treatment failure results in poorer prognosis with devastating repercussions for the patients, carers and broader society. Our study evaluated the clinical benefits of a pharmacogenetic intervention for the personalisation of antipsychotic treatment. Pharmacogenetic information in key CYP polymorphisms was used to adjust clinical doses in a group of patients who started or switched treatment with antipsychotic drugs (PharmG+, N = 123), and their results were compared with those of a group of patients treated following existing clinical guides (PharmG-, N = 167). There was no evidence of significant differences in side effects between the two arms. Although patients who had their antipsychotic dose adjusted according to CYPs polymorphisms (PharmG+) had a bigger reduction in side effects than those treated as usual (PharmG-), the difference was not statistically significant (p > 0.05 for all comparisons). However, PharmG+ patients treated with CYP2D6 substrates that were carriers of CYP2D6 UMs or PMs variants showed a significantly higher improvement in global, psychic and other UKU side effects than PharmG- patients (p = 0.02, p = 0.05 and p = 0.01, respectively). PharmG+ clozapine treated patients with CYP1A2 or CYP2C19 UM and PMs variants also showed higher reductions in UKU scores than PharmG- clozapine patients in general. However, those differences were not statistically significant. Pharmacogenetic interventions may improve the safety of antipsychotic treatments by reducing associated side effects. This intervention may be particularly useful when considering treatment with antipsychotics with one major metabolic pathway, and therefore more susceptible to be affected by functional variants of CYP enzymes.

Testing the efficacy of INtegral Cognitive REMediation (INCREM) in major depressive disorder: study protocol for a randomized clinical trial.

BACKGROUND: Given the limitation of pharmacological treatments to treat cognitive symptoms in patients with Major Depressive Disorder (MDD), cognitive remediation programs has been proposed as a possible procognitive intervention but findings are not conclusive. This study investigates the efficacy of an INtegral Cognitive REMediation (INCREM) that includes a combination of a Functional Remediation (FR) strategy plus a Computerized Cognitive Training (CCT) in order to improve not only cognitive performance but also the psychosocial functioning and the quality of life. METHODS: A single blind randomized controlled clinical trial in 81 patients with a diagnosis of MDD in clinical remission or in partial remission. Participants will be randomized to one of three conditions: INCREM (FR + CCT), Psychoeducation plus online games and Treatment As Usual (TAU). Intervention will consist in 12 group sessions, of approximately 110 min once a week. The primary outcome measure will be % of change in psychosocial functioning after treatment measured by the Functional Assessment Short Test (FAST); additionally, number of sick leaves and daily activities will also be recorded as pragmatic outcomes. DISCUSSION: To our knowledge, this is the first randomized controlled clinical trial using a combination of two different approaches (FR + CCT) to treat the present cognitive deficits and to promote their improvements into a better psychosocial functioning. TRIAL REGISTRATION: Clinical Trials NCT03624621 . Date registered 10th of August 2018 and last updated 24th August 2018.

Efficacy of quetiapine XR vs. placebo as concomitant treatment to mood stabilizers in the control of subthreshold symptoms of bipolar disorder: Results from a pilot, randomized controlled trial.

Patients with bipolar disorder (BD) do not always achieve full remission between episodes. Subthreshold symptoms (depressive, manic or mixed) represent a major cause of relapse and disability in these patients. Immediate release (IR) and extended release (XR) formulations of quetiapine are both indicated for short and long-term treatment of BD. The aim of this study was to evaluate the efficacy of quetiapine XR vs placebo in subthreshold symptomatology when added to previous mood stabilizer treatment. A pilot phase IIIB, multicentre, prospective, placebo controlled, randomized, double blinded study of 12 weeks follow-up was performed (NCT01197846). Patients were randomized to quetiapine XR 300mg or placebo once daily. The primary outcome was the mean change between quetiapine XR and placebo from baseline to study endpoint (week 6) in the Montgomery-Åsberg Depression Rating Scale (MADRS). Quetiapine XR 300mg (n=16) significantly improved depressive subthreshold symptoms compared with placebo (n=16) after 6 weeks (P=0.021). Early response (reduction of at least the 20% of the MADRS total score) and remission rate (reduction in MADRS total score <8 and YMRS<8) did not show differences between groups. Quetiapine XR did not show superiority vs placebo when evaluating subthreshold manic symptoms, instead it was superior when evaluating functioning (GAF score) in BD type I patients (P=0.005). The most common adverse events were somnolence (9.1%), increased appetite, dry mouth and dizziness (6.8%). Quetiapine XR 300mg once daily was significantly more effective than placebo in depressive subthreshold symptoms. Adverse events were consistent with the known side effects of quetiapine.

Farmacogenética de las reacciones adversas a los antipsicóticos en pacientes con esquizofrenia / Pharmacogenetics of antipsychotic adverse effects in patients with schizophrenia

Esta revisión se centra en los conocimientos actuales en el campo de la farmacogenética que tienen relación con las reacciones adversas a los antipsicóticos en pacientes con esquizofrenia. En el momento actual hay numerosas investigaciones que han intentado determinar variantes genéticas que permitan predecir el riesgo individual de padecer efectos secundarios al tratamiento con antipsicóticos. Múltiples estudios determinan que polimorfismos de las enzimas del citocromo P450 y de los receptores dopaminérgicos pueden estar relacionados con un mayor riesgo de trastornos del movimiento inducidos por antipsicóticos. Por otro lado, tanto el sistema serotoninérgico como la leptina se han relacionado con el control del apetito, y variantes del receptor 5-HT2C y del gen de la leptina pueden estar asociadas al aumento de peso en el contexto del tratamiento con estos fármacos. Estudios centrados en el riesgo de agranulocitosis con clozapina han concluido que variantes del sistema mayor de histocompatibilidad pueden ser responsables de un incremento del riesgo de aparición de esta reacción adversa (AU)

This review focuses on the current knowledge on pharmacogenetics related to adverse reactions to antipsychotics in patients with schizophrenia. Numerous studies have attempted to identify genetic variants that predict individual risk of side effects during antipsychotic treatment. Several of these studies have determined that polymorphisms of cytochrome P450 enzymes and dopamine receptors may be related to an increased risk of movement disorders induced by antipsychotics. On the other hand, the serotonergic and leptin systems can regulate food intake, and polymorphisms in the 5-HT2C and leptin genes have been associated with antipsychotic-induced weight gain. Several studies have investigated the risk of agranulocytosis during clozapine treatment, and concluded that genetic variants of the major histocompatibility complex may be related with and increased risk of agranulocytosis (AU)

Tratamiento de la depresión con bupropión en monoterapia / No disponible

No disponible

Papel de bupropión en el tratamiento de la depresión resistente. Manejo de bupropión en combinación / No disponible

No disponible

Uso de bubropión en pacientes ancianos / No disponible

No disponible

Bupropión y patología dual / No disponible

No disponible

Tolerancia y perfil de efectos secundarios de bupropión / No disponible

No disponible

Bupropión y depresión bipolar / No disponible

No disponible

A double-blind, randomized, placebo-controlled prophylaxis trial of oxcarbazepine as adjunctive treatment to lithium in the long-term treatment of bipolar I and II disorder.

We evaluated the prophylactic efficacy and the long-term tolerability of oxcarbazepine administration in the treatment of bipolar I and II disorder as an adjunctive therapy to lithium. We conducted a 52-wk, double-blind, randomized, placebo-controlled, parallel-group, multicentre, clinical trial. Bipolar I and II DSM-IV outpatients, having had two or more episodes in the last year, but currently being in remission, were randomly assigned on a 1:1 ratio to oxcarbazepine (n=26) or placebo (n=29) as adjuncts to ongoing treatment with lithium. The primary efficacy variable was the length of the remission period assessed by means of the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS). Other assessments were the Clinical Global Impression (CGI-BP-M), functional activity (GAF), anxiety (HAMA) and impulsiveness (BIS-11). The average time until first recurrence of any type was 19.2+/-13.9 wk and 18.6+/-17.0 wk for oxcarbazepine and placebo respectively (p=0.315). Ten (38.46%) patients had a recurrence of any kind in the oxcarbazepine group vs. 17 (58.62%) in the placebo group (p=0.1354). There was a trend for depressive episodes being less likely in the oxcarbazepine group compared to the placebo group (11.54% and 31.03% respectively, p=0.085), and for better functionality with the GAF (p=0.074). Impulsivity was significantly better prevented by oxcarbazepine (p=0.0443). Overall, oxcarbazepine was well tolerated. This pilot, randomized clinical trial, suggests that oxcarbazepine might have some prophylactic efficacy with regards to impulsivity and perhaps mood episodes in patients taking lithium, although further, adequately powered controlled trials are needed to confirm these findings.

Trastorno esquizofreniforme. Estudio prospectivo de 5 años de seguimiento / Eschizophreniform disorder. A five year prospective study

Introducción: Estudio prospectivo de cinco años cuyo objetivo es evaluar la estabilidad temporal del diagnóstico de trastorno esquizofreniforme (TE) provisional en pacientes ingresados por un primer episodio psicótico. Se evalúan también las propiedades predictivas de las características de buen pronóstico. Material y métodos: La muestra consta de 38 pacientes (23 hombres y 15 mujeres) ingresados en el hospital entre 1996 y 1998. Se realizaron cuatro entrevistas de seguimiento: en el primer, segundo, tercer y quinto año. Los pacientes fueron evaluados mediante: la Brief Psychiatric Rating Scale (BPRS), la Escala de Evolución de Strauss-Carpenter, los diagnósticos en los ejes I-IV, la Escala de Evaluación de la Actividad Global (EEAG), el tratamiento en curso y variables demográficas. Resultados: 27 pacientes completaron el seguimiento de cinco años. El 25,9 por ciento mantenían el diagnóstico de TE a los cinco años y el 59,2 por ciento fueron clasificados dentro del espectro esquizofrénico. La presencia en el primer ingreso de un mínimo de dos características de buen pronóstico se asoció con una mejor evolución a los cinco años, pero no se asoció al mantenimiento del diagnóstico de TE. Después de cinco años de seguimiento, los pacientes que mantuvieron el diagnóstico de TE presentaron mejor evolución que los pacientes esquizofrénicos. Conclusiones: El diagnóstico TE provisional fue muy inestable a los cinco años de seguimiento. La mayoría de pacientes continuaron presentando síntomas y cumplieron criterios de esquizofrenia o trastorno esquizoafectivo. Los hallazgos sugieren una asociación entre las características de buen pronóstico y una mejor evolución, aunque no se observa asociación con el mantenimiento del diagnóstico TE (AU)