Patterns of pharmacological maintenance treatment in a community mental health services bipolar disorder cohort study (SIN-DEPRES).

Maintenance therapy in bipolar disorder (BD) is usually required to prevent relapses and improve residual symptoms. Therefore, in this study, we describe patterns of pharmacological maintenance treatment and identify associated clinical features. This prospective multicentre epidemiological study recruited a cohort of 739 consecutive out-patients with clinically stable BD. Clinical stability was assessed at baseline with the Clinical Global Impression scale for BD and depressive symptoms with the Hamilton Depression Rating Scale. Psychotropic medications were classified and analysed according to their mechanism as well as use. Logistic regression models were used to examine the associations between pharmacological strategies and clinical features. Longer time since last episode [odds ratio (OR) 1.002, p < 0.0001] and family history of psychiatric disorders (OR 1.911, p = 0.028) were associated with lithium in monotherapy; manic polarity of the most recent episode (OR 3.300, p = 0.006) and longer duration of clinical stability (OR 1.009, p = 0.034) with antipsychotic in monotherapy; depressive polarity of the most recent episode (OR 2.567, p = 0.003) and bipolar II disorder diagnosis (OR 2.278, p = 0.008) with antidepressant combination; no ongoing psychiatric co-morbidity (OR 0.230, p = 0.004) with lithium and anticonvulsant; manic polarity of the most recent episode (OR 3.774, p < 0.0001) with lithium and antipsychotic; manic polarity of the most recent episode (OR 2.907, p = 0.028) with lithium, anticonvulsant and antipsychotic. The pharmacological patterns followed published recommendations, except for the excessive use of antidepressants. This study reveals clinical factors closely related to prescription patterns.

Subsyndromal Depressive Symptoms in Bipolar II Disorder: a Community Mental Health Services Cohort Study (SIN-DEPRES) / Síntomas depresivos subsintomáticos en trastorno bipolar II: un estudio de cohorte de servicios de salud comunitarios

Objectives: The aim of this study was to assess the prevalence and the impact of subclinical depressive symptoms (SDS) on the functional outcome of bipolar II (BD) outpatients in remission. Methods: Cross-sectional and prospective 16-week study of a cohort of 739 euthymic BD patients included by 94 investigators in Spain. Clinical stability was assessed at baseline and week 16 with the Clinical Global Impression scale for BD (CGI-BP-M), depressive symptoms at baseline with the Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Scale (MADRS) and the self-applied Center for Epidemiologic Studies-Depression Scale (CES-D). Functional status was evaluated with the Social and Occupational Functioning Assessment Scale (SOFAS) and Social Adaptation Self-evaluation Scale (SASS). Results: The sample of type II BD was composed by 202 patients. SDS were detected in 21.3% of patients (95% IC =15.9 to 27.6) at baseline. In apparently symptom-free patients, the incidence of SDS after 16 weeks was 29% (MADRS >7). At baseline, SDS patients compared to non-SDS presented poorer social-occupational performance (SOFAS mean difference -13.3, 95% CI from -17.1 to -9.5) and poorer social adjustment (SASS mean difference -4.3, 95% CI from -7.0 to -1.7). Depressive symptoms were inversely related to functional status and social adjustment: MADRS-SOFAS correlation coefficients r = -0.55 (p<0.0001) and MADRS-SASS correlation coefficients r = -0.43 (p<0.0001). The self-applied questionnaire identified additional cases with depressive symptoms at baseline, showing a SDS-Total prevalence of 51% identified by any method. A MADRS score 5 showed 0.75 sensitivity and 0.69 specificity in the detection of cases with possible SDS based on self-reported results as gold standard. Conclusions: Depressive symptoms in apparently remitted type II BD outpatients are common and as frequent as in other BD subtypes. These subclinical symptoms result in adverse occupational outcome and social maladjustment. MADRS and self-applied questionnaires during follow-up visits may provide important information about type II BD patients’ mood status and functionality.

Objetivos: Evaluar la prevalencia y el impacto de los síntomas depresivos subclínicos (SDS) en el resultado funcional de pacientes externos de bipolaridad II (TB) en remisión. Métodos: Estudio transversal y prospectivo, de 16 semanas de duración, de una cohorte de 739 pacientes eutímicos de TB incluidos por 94 investigadores en España. La estabilidad clínica se evaluó, en la línea base y en la semana 16, con la Escala Impresión Global Clínica para TB (CGI-BP-M); los síntomas depresivos, en la línea base, con la Escala de Calificación de la Depresión de Hamilton (HDRS), la Escala Montgomery-Asberg (MADRS) y la Escala Autoaplicada para la Depresión del Centro de Estudios Epidemiológicos (CES-D). El estado funcional se evaluó con la Escala de Evaluación del Funcionamiento Social y Ocupacional (SOFAS), y la Escala de Autoevaluación de la Adaptación Social (SASS). Resultados: La muestra de TB tipo II estuvo compuesta de 202 pacientes. Se detectaron SDS en 21,3% de los pacientes (95% IC = 15,9 a 27,6) en la línea base. En pacientes que aparentemente no presentaban síntomas, la incidencia de SDS después de 16 semanas era de un 29% (MADRS>7). En la línea base, los pacientes SDS, en comparación con los no SDS, demostraban un desempeño social-ocupacional más pobre (diferencia media SOFAS -13,3, 95% IC de -17,1 a -9,5) y un ajuste social más pobre (diferencia media SASS -4,3, 95% IC de -7,0 a -1,7). Los síntomas depresivos estaban relacionados inversamente con el estado funcional y el ajuste social: coeficientes de correlación MADRS-SOFAS r = -0,55 (p<0,0001) y coeficientes de correlación MADRS-SASS r = -0,43 (p<0,0001). El cuestionario autoaplicado identificó casos adicionales con síntomas depresivos en la línea base, y mostró una prevalencia total de SDS de 51% identificada por cualquier método. Un puntaje MADRS ≥ 5 mostró una sensibilidad de 0,75 y una especificidad de 0,69 en la detección de casos con posible SDS, basándose en los resultados autoreportados como el estándar de oro. Conclusiones: Los síntomas depresivos en pacientes externos de TB de tipo II aparentemente en remisión son comunes y son tan frecuentes como para los demás subtipos de TB. Estos síntomas subclínicos tienen resultados ocupacionales adversos así como inadaptación social. La MADRS y los cuestionarios autoaplicados durante las visitas de seguimiento pueden ofrecer información importante acerca del estado de ánimo y la funcionalidad del paciente de TB tipo II.

Detection of subclinical depression in bipolar disorder: a cross-sectional, 4-month prospective follow-up study at community mental health services (SIN-DEPRES).

OBJECTIVE: The aim of this study was to assess the prevalence and the impact of depressive symptoms on the functional outcome of bipolar disorder outpatients in remission. METHOD: A cross-sectional, prospective 16-week study of a cohort of 739 euthymic bipolar disorder patients (DSM-IV-TR criteria) recruited by 94 investigators was conducted. Clinical stability was assessed at baseline and at week 16 with the modified Clinical Global Impressions Scale-Bipolar Version, and depressive symptoms were assessed at baseline with the 17-item Hamilton Depression Rating Scale (HDRS-17 [primary endpoint measure]), the Montgomery-Asberg Depression Rating Scale (MADRS), and the self-applied Center for Epidemiologic Studies-Depression Scale (CES-D). Functional status was evaluated with the Social and Occupational Functioning Assessment Scale (SOFAS) and Social Adaptation Self-evaluation Scale (SASS). The study was conducted from April 2006 to March 2007. RESULTS: Subclinical depressive symptoms (SDS) were detected on the HDRS-17 in 16.9% of the sample. In symptom-free patients, the incidence of new SDS after 16 weeks was 20% (MADRS score > 7). At baseline, SDS patients compared to non-SDS patients presented with poorer social-occupational performance (SOFAS score mean difference, -11.9; 95% CI, -14.2 to -9.6) and poorer social adjustment (SASS score mean difference, -5.6; 95% CI, -7.1 to -4.1). Depressive symptoms were inversely related to functional status and social adjustment: MADRS-SOFAS correlation coefficients, r = -0.54 (P < .0001), and MADRS-SASS correlation coefficients, r = -0.42 (P < .0001). The self-applied survey identified additional cases with depressive symptoms, showing an SDS total prevalence of 44.9%. CONCLUSIONS: Depressive symptoms in apparently remitted bipolar disorder outpatients are not rare and result in a decline in occupational outcome and social maladjustment.

Relapse prevention in schizophrenia and schizoaffective disorder with risperidone long-acting injectable vs quetiapine: results of a long-term, open-label, randomized clinical trial.

Chronic management of schizophrenia and schizoaffective disorders is frequently complicated by symptomatic relapse. An open-label, randomized, active-controlled, 2-year trial evaluated 710 patients with schizophrenia or related disorders who were switched from stable treatment with oral risperidone, olanzapine, or conventional neuroleptics to risperidone long-acting injectable (RLAI) or oral quetiapine. Primary effectiveness evaluation was time-to-relapse. Safety evaluations included adverse events (AEs) reported for the duration of the study, Extrapyramidal Symptom Rating Scale (ESRS), clinical laboratory tests, and vital signs. A total of 666 patients (n=329 RLAI, n=337 quetiapine) were evaluable for effectiveness measures. Baseline demographics were similar between treatment groups. Kaplan-Meier estimate of time-to-relapse was significantly longer with RLAI (p<0.0001). Relapse occurred in 16.5% of patients with RLAI and 31.3% with quetiapine. RLAI and quetiapine were both safe and well tolerated. Weight gain affected 7% of patients with RLAI and 6% with quetiapine, with mean end point increases of 1.25±6.61 and 0±6.55 kg, respectively. There were no significant between-group differences in weight gain. ESRS total scores decreased similarly after randomization to either RLAI or quetiapine. Extrapyramidal AEs occurred in 10% of patients with RLAI and 6% with quetiapine. Treatment-emergent potentially prolactin-related AEs were reported in 15 (5%) patients with RLAI and 5 (2%) patients with quetiapine; hyperprolactinemia was reported in 43 (13.1%) patients with RLAI and 5 (1.5%) patients with quetiapine. Somnolence occurred in 2% of patients with RLAI and 11% with quetiapine. To our knowledge, this is the first report of a randomized clinical trial directly comparing relapse prevention with a second-generation long-acting injectable antipsychotic and oral therapy. Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was significantly longer in patients randomized to RLAI compared with those randomized to oral quetiapine. Both antipsychotics were generally well tolerated.

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.