A prospective longitudinal study searching for predictors of response to group psychoeducation in bipolar disorder.

BACKGROUND: The efficacy of adjunctive group psychoeducation in bipolar disorder has been proven although treatment response differ among individuals. The aim of this study was to characterize responders and non-responders to group psychoeducation in order to identify baseline variables that could predict treatment response. METHODS: The sample was composed of 103 medicated euthymic patients with bipolar disorder referred to 21 sessions of group psychoeducation (6 months). Sociodemographic and clinical variables, temperament, circadian rhythms, BDNF, cognitive and psychosocial functioning were collected. At the 18-month endpoint, the patients were split in two groups on the basis of having suffered any recurrence. Significant group differences were included in a logistic regression analysis. RESULTS: Ninety patients out of 103 engaged in group psychoeducation, 47 of whom (52.2%) responded to psychoeducation and 43 (47.8%) did not. Recurrences occurred more often in the follow-up, the most common being depression. Responders and non-responders differed in gender, age at diagnosis, latency of diagnosis, temperament, attention composite score and BDNF. Lower age at diagnosis of bipolar disorder, lower cyclothimic temperament scores and being male -which was associated with bipolar type I and a trend to more previous manic episodes- were significantly related to a better response to psychoeducation in the regression analysis. LIMITATIONS: No control group. CONCLUSIONS: This study identifies age at diagnosis as a significant modifiable risk factor of treatment response, highlighting the need for early identification of bipolar disorder. Existing programs should be adjusted to the characteristics of specific subpopulations in the framework of a personalized approach.

An Emergency Department-Initiated Intervention to Lower Relapse Risk after Attempted Suicide.

OBJECTIVE: According to randomized trials, contact after a suicide attempt lowers relapse risk. However, effectiveness studies based on real clinical data can provide additional external validity. METHOD: We conducted an observational study to determine if an emergency department (ED)-initiated intervention for suicide attempt risk reduction, consisting on scheduling a single added appointment within 7 days after discharge following a suicide attempt, can reduce the risk of relapse. The study included 1,775 patients who had been treated at a general hospital ED due to a suicide attempt. The principal outcome measure was ED return after a new attempt. We obtained Kaplan-Meier survival functions and used Cox proportional hazard regression models to estimate unadjusted and adjusted risks of relapse by treatment phase. Covariates included: age, gender, history of suicide attempts, history of psychiatric disorders, concurrent alcohol/drug abuse, number of attempts during follow-up, admission as an inpatient and family support. RESULTS: A total of 497 (22.5%) attempts were followed by a relapse. Subjects exposed to the studied intervention had a lower risk of relapse after a suicide attempt, with a 24% adjusted risk reduction estimate. CONCLUSION: Our real-world results suggest that an additional early appointment, scheduled before discharging suicide attempters, reduces suicide reattempt risk.

Long-acting injectable antipsychotics for the treatment of schizophrenia in Spain. / Antipsicóticos inyectables de liberación prolongada para el tratamiento de la esquizofrenia en España.

Antipsychotics are an essential component in the treatment of schizophrenia. Long-acting injectable formulations (LAI) arose to improve adherence with the associated potential of reducing the risk of relapse. The objective of this article is to analyze the use of LAI antipsychotics in Spain, which is similar to other European countries but with a predominance of the use of second generation LAI, to discuss the possible causes of prescribing differences with respect to other countries (including organizational aspects, attitudes of psychiatrists, patients and family members, and clinical practice guidelines), and to discuss their use in acute psychiatric units, first episode, and in children and adolescents. In our view, while it is necessary to increase existing evidence regarding the advantages of LAI antipsychotics and the differentiation between LAI antipsychotics currently available, their use will likely continue to grow driven by clinical experience.

Quality indicators in the treatment of patients with depression, bipolar disorder or schizophrenia. Consensus study. / Indicadores de calidad en el tratamiento de pacientes con depresión, trastorno bipolar o esquizofrenia. Estudio de consenso.

OBJECTIVE: To define a set of indicators for mental health care, monitoring quality assurance in schizophrenia, depression and bipolar disorders in Spain. MATERIAL AND METHOD: Qualitative research. Consensus-based study involving 6 psychiatrists on the steering committee and a panel of 43 psychiatrists working in several health services in Spain. An initial proposal of 44 indicators for depression, 42 for schizophrenia and 58 for bipolar disorder was elaborated after reviewing the literature. This proposal was analysed by experts using the Delphi technique. The valuation of these indicators in successive rounds allowed those with less degree of consensus to be discarded. Feasibility, sensitivity and clinical relevance were considered. The study was carried out between July 2015 and March 2016. RESULTS: Seventy indicators were defined by consensus: 17 for major depression, 16 for schizophrenia, 17 for bipolar disorder and 20 common to all three pathologies. These indicators included measures related to adequacy, patient safety, exacerbation, mechanical restraint, suicidal behaviour, psychoeducation, adherence, mortality and physical health. CONCLUSIONS: This set of indicators allows quality monitoring in the treatment of patients with schizophrenia, depression or bipolar disorder. Mental health care authorities and professionals can use this proposal for developing a balanced scorecard adjusted to their priorities and welfare objectives.

Depressive symptoms in early- and late-onset older bipolar patients compared with younger ones.

OBJECTIVES: The aim of this study was to determine clinical and outcome differences between older bipolar patients with early onset (EO) and late onset (LO) of the illness and between younger and EO older patients with a bipolar disorder under long-term treatment in an outpatient clinical setting. METHODS: Three hundred ninety-five bipolar I and II outpatients were followed up for up to 7.7 years. Of these, 213 younger (<50 years) and 88 older (>60 years) patients were included. In the older subsample, 50 EO patients (onset <50 years) versus 38 LO patients (≥50 years) were analyzed. Likewise, younger versus EO older patients were compared. RESULTS: The likelihood of LO older patients of being bipolar II was higher than for EO older patients. They were also diagnosed earlier than EO older patients. No other clinical differences at baseline and at the prospective follow-up were found. Compared with younger patients, EO older patients had more frequent depressive symptoms at baseline, suffered more major depressive episodes in the previous year and in the prospective follow-up, received more antidepressants at baseline, had higher rates of medical comorbid conditions and were less likely to be tobacco smokers. CONCLUSIONS: Older patients constitute a meaningful proportion of bipolar patients under treatment. EO older patients suffered significantly from more frequent depressive symptoms than younger ones. LO older patients were predominantly bipolar II. So as bipolar illness progressed, depressive symptomatology became more frequent and manic episodes were less severe. Copyright © 2016 John Wiley & Sons, Ltd.

The contribution of depressive symptoms to slowness of information processing in relapsing remitting multiple sclerosis.

BACKGROUND: Slowness of information processing has been suggested as a fundamental factor modulating cognitive impairment in multiple sclerosis (MS). However, the contribution of depressive symptoms (DS) to slowness remains unclear. One of the most accepted hypotheses on the impact of depression on the general population suggests that depression interferes only with tasks requiring high cognitive demands. However, no studies have investigated if the same pattern occurs in MS. OBJECTIVE: The aim of this study was to determine the profile of the contribution of DS to slowness. METHODS: Four Reaction Time (RT) tasks requiring an increasing level of cognitive demands were administered to 35 relapsing remitting MS patients with DS, 33 MS patients without DS, 17 depressed non-MS patients and 27 controls. RESULTS: MS patients without DS obtained longer RTs than controls in all the tasks. On the contrary, depressed non-MS patients were slower than controls only in the most demanding task. Finally, MS patients with DS were slower than MS patients without DS not only in the most demanding task but also in the task requiring a lower level of cognitive demands. CONCLUSION: The contribution of DS to slowness depends on the level of cognitive demands. However, its impact on MS is more deleterious than on the general population.

Bipolar disorders in the new DSM-5 and ICD-11 classifications.

UNLABELLED: The DSM-5 and ICD-11 classifications, the latter still under development, are aimed at harmonizing the diagnoses of mental disorders. A critical review is presented in the issues that can converge or separate both classifications regarding bipolar disorders, and those conditions­included in depressive disorders­with special relevance for bipolar (e.g. major depressive episode). The main novelties include the incorporation of dimensional parameters to assess the symptoms, as well as the sub-threshold states in the bipolar spectrum, the consideration of new course specifiers such as the mixed symptoms, the elimination of mixed episodes, and a more restrictive threshold for the diagnosis of hypo/mania. The most noticeable points of convergence are the inclusion of bipolar II disorder in ICD-11 and the additional requirement of an increase in activity, besides mood elation or irritability, for the diagnosis of hypo/mania in both classifications. The main differences are, most likely keeping the mixed depression and anxiety disorder diagnostic category, maintaining bereavement as exclusion criterion for the depressive episode, and maintaining the mixed episode diagnosis in bipolar disorder in the forthcoming ICD-11. CONCLUSION: Since DSM-5 has already been published, changes in the draft of ICD-11, or ongoing changes in DSM-5.1 will be necessary to improve the harmonization of psychiatric diagnoses.

Mindfulness-based cognitive therapy versus psychoeducational intervention in bipolar outpatients with sub-threshold depressive symptoms: a randomized controlled trial.

BACKGROUND: The presence of depressive subsyndromal symptoms (SS) in bipolar disorder (BD) increases the risk of affective relapse and worsens social, cognitive functioning, and quality of life. Nonetheless, there are limited data on how to optimize the treatment of subthreshold depressive symptoms in BD. Mindfulness-Based Cognitive Therapy (MBCT) is a psychotherapeutic intervention that has been shown effective in unipolar depression. The assessment of its clinical effectiveness and its impact on biomarkers in bipolar disorder patients with subsyndromal depressive symptoms and psychopharmacological treatment is needed. METHODS/DESIGN: A randomized, multicenter, prospective, versus active comparator, evaluator-blinded clinical trial is proposed. Patients with BD and subclinical or mild depressive symptoms will be randomly allocated to: 1) MBCT added to psychopharmacological treatment; 2) a brief structured group psychoeducational intervention added to psychopharmacological treatment; 3) standard clinical management, including psychopharmacological treatment. Assessments will be conducted at screening, baseline, post-intervention (8 weeks) and 4 month follow-up post-intervention. The aim is to compare MBCT intervention versus a brief structured group psychoeducation. Our hypothesis is that MBCT will be more effective in reducing the subsyndromal depressive symptoms and will improve cognitive performance to a higher degree than the psychoeducational treatment. It is also hypothesized that a significant increase of BDNF levels will be found after the MBCT intervention. DISCUSSION: This is the first randomized controlled trial to evaluate the effects of MBCT compared to an active control group on depressive subthreshold depressive symptoms in patients with bipolar disorder. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02133170. Registered 04/30/2014.

Seasonality, smoking and history of poor treatment compliance are strong predictors of dropout in a naturalistic 6 year follow-up of bipolar patients.

Bipolar disorder is a highly recurrent disease which requires long-term treatment. Dropout is a major problem, poorly understood. The objectives of this study were to know the risk of dropout of a cohort of bipolar patients under ambulatory treatment and to identify the clinical profile of patients more likely to abandon the follow-up. A sample of 285 BD I and II patients was followed up for a mean of 2.87 years. A significant proportion of patients failed regular follow-up. The dropout rates were 6.3 % at three months, 12.7 % at 6 months, and 17.6, 27.2, 37.3, 44.0, 47.2 and 49.0 % at 1, 2, 3, 4, 5 and 6 years respectively. Very few variables at baseline predicted dropout. Patients under 35 years of age were more likely to dropout than older cases. Seasonality, smoking and specially history of poor treatment compliance were strong predictors of dropout. Given the magnitude of dropout, additional early clinical interventions should be considered for high-risk patients.

Understanding bipolar disorder in late life: clinical and treatment correlates of a sample of elderly outpatients.

The aim of this study was to examine the demographic, clinical, and treatment correlates of bipolar disorder (BD) in outpatients 65 years or older and to compare patients with BD subtype I (BD-I) versus BD subtype II (BD-II) and patients with early onset (EO; <=50 years old) versus late onset (LO; >50 years old) of the illness. Sixty-nine consecutive outpatients with BD were included. Diagnosis was delayed for a mean of 14.1 years, significantly longer in patients with EO (18.6 years) than with LO (3.3 years). Mild to moderate depressive symptoms were detected in 29% of the patients. The patients were receiving a mean of 3 different psychotropic medications. Antidepressantswere more frequently prescribed to patients with BD-II than to patients with BD-I (75.80% vs. 48.60%) and to patients with EO (71.7%) than to LO (35.3%). Geriatric BD has similar clinical characteristics with those of younger ages, and these do not seem to greatly differ with subtype or age of onset.

Suboptimal treatment adherence in bipolar disorder: impact on clinical outcomes and functioning.

BACKGROUND: The primary aim of this study was to assess drug treatment adherence in patients with bipolar disorder and to identify factors associated with adherence. The secondary aim was to analyze the impact of suboptimal adherence on clinical and functional outcomes. METHODS: A cross-sectional study was conducted in a sample of outpatients receiving an oral antipsychotic drug. Medication adherence was assessed combining the 10-item Drug Attitude Inventory, the Morisky Green Adherence Questionnaire, and the Compliance Rating Scale. Logistic regression was used to determine significant variables associated with suboptimal adherence to medication. RESULTS: Three hundred and three patients were enrolled into the study. The mean age was 45.9 ± 12.8 years, and 59.7% were females. Sixty-nine percent of patients showed suboptimal adherence. Disease severity and functioning were significantly worse in the suboptimal group than in the adherent group. Multivariate analysis showed depressive polarity of the last acute episode, presence of subsyndromal symptoms, and substance abuse/dependence to be significantly associated with suboptimal treatment adherence (odds ratios 3.41, 2.13, and 1.95, respectively). CONCLUSION: A high prevalence of nonadherence was found in an outpatient sample with bipolar disorder. Identification of factors related to treatment adherence would give clinicians the opportunity to select more adequately patients who are eligible for potential adherence-focused interventions.

[Variables associated with disability in elderly bipolar patients on ambulatory treatment]. / Discapacidad en pacientes bipolares ancianos en tratamiento ambulatorio. Variables asociadas.

INTRODUCTION: Studies on adult bipolar patients have demonstrated a disability associated with the bipolar disorder, even in euthymic patients, but there is a lack of data in the elderly population. MATERIAL AND METHOD: A cross-sectional, multicentre study on a consecutive sample of ambulatory bipolar patients (DSM-IV-TR criteria), aged 65 years or over. Retrospective and cross-sectional sociodemographic and clinical data were collected, as well as the Clinical Global Impression for Bipolar Modified scale (CGI-BP-M) and the level of disability using the World Health Organisation Disability Assessment Schedule (WHO/DAS). The disability was assessed globally and by areas. The presence of a moderate to maximum disability compared to a mild to no disability was considered a dependent variable. RESULTS: A moderate to maximum global disability was present in 43.6% of the sample. By areas, occupational functioning was the area most frequently affected, and personal care the least affected. The only variables which were associated with disability were the presence of medical comorbidity (P = .01), increased age (P = .005) global clinical severity (P = .0001) and in the depressive pole (P = .03). There was no relationship between clinical subtype, duration of the disease, number of previous episodes, number of hospitalisations, or other clinical variables and the degree of disability. CONCLUSIONS: These data underline the need to establish specific therapeutic strategies in the approach to depressive symptoms and medical comorbidity, with the aim of minimising the disability in elderly bipolar patients. Given the lack of current data, new studies are needed with larger samples and control groups.

Predictors of recurrence in bipolar disorders in Spain (PREBIS study data).

OBJECTIVE: The objective of this study was to evaluate demographic, psychosocial and clinical predictors of mood recurrences in bipolar disorder (BD) euthymic outpatients followed-up for 12 months in a naturalistic setting. METHODS: The study included 595 consecutive BD patients, diagnosed according to DSM-IV-TR criteria, in clinical remission at baseline. Quarterly assessments were scheduled. Clinical evaluation as well as mood and functioning psychometric evaluations were performed. We applied logistic regression analysis to determine predictors of presenting an affective recurrence, and Cox regression analysis to examine the association between individual predictors and time to affective recurrence. RESULTS: Of the 593 patients finally included (60% women, 84.5% BD I), 141 (23.78%) had at least a recurrence during the 12 months follow-up. Time until 25% of the patients experienced a recurrence was 12 months (95% CI: 9.14-undetermined). In multivariate analysis, factors significantly related to relapse were living setting (p=0.002) and total number of previous episodes (p=0.01). Residents in mixed urban/rural catchment areas had 57% more risk than dwellers of cities with more than 100,000 people, and a higher number of previous episodes also increased the relapse risk. A shorter time to relapse was related to job status (p=0.004) and to living setting (p=0.002). CONCLUSION: In our sample, living in environments of less than 100,000 inhabitants and having more previous affective episodes were related to an increased relapse risk in BD, and job status and living setting were related to a shorter time to relapse. LIMITATIONS: No specific contemporary practice guidelines were used. Drug treatment and plasma levels, although measured, were not registered.

[Diagnostic delay and differences by sex and clinical subtype in a cohort of outpatients with bipolar disorder]. / Retraso diagnóstico y diferencias por sexo y subtipo clínico en una cohorte de pacientes ambulatorios con trastorno bipolar.

INTRODUCTION: We describe the clinical and sociodemographic features at baseline of a cohort of bipolar patients included in a prospective study. METHODS: A total of 296 consecutive outpatients with bipolar disorder were recruited. Diagnosis relied on clinical judgment according to DSM-IV-TR criteria and the semi-structured MINI Interview. Retrospective data on the course of the disease and cross-sectional data on social adaptation (Social Adaptation Adjustment Self-Assessment Scale (SASS) and affective symptoms were collected. Affective symptomatology (euthymia, subsyndromal symptoms and episodes) was studied according to clinical criteria and the Hamilton Depression and Young rating scales. Differences between type I and II bipolar patients and between men and women were analyzed. RESULTS: The mean age was 48.8 years (95% CI 47.2-50.4); 56.8% were women and 43.2% were men. A total of 65.2% had a diagnosis of type I bipolar disorder and 23.3% of type II; 49.8% of the sample were euthymic, 32.7% had subsyndromal symptoms and 17.5% had had an affective episode. Diagnostic delay was 9.3 years (95% CI 8.2-10.3). In patients with type II bipolar disorder, the mean age (54.4 years; 95% CI 50.9-57.9 vs. 47.7 years; 95% CI 45.8-49.7, p=0.007), age at onset of illness (35.7 years; 95% CI 31.8-39.7 vs. 29.8 years; 95% CI 28-31.6, p=0.008) and age at diagnosis (47.7 years; 95% CI 44-51.3 vs. 37.9; 95% CI 35.9-39.8, p<0.0001) were higher than in patients with type I bipolar disorder. Manic polarity in the initial episode and psychotic episodes were more frequent in men, while depressive episodes and hypothyroidism were more frequent in women. CONCLUSIONS: Our results confirm data published in our environment on sociodemographic and clinical variables but diagnostic delay in our study was longer. Compared with American samples, age at onset and at diagnosis were higher in our sample but comorbidity was much lower.

Time spent with symptoms in a cohort of bipolar disorder outpatients in Spain: a prospective, 18-month follow-up study.

OBJECTIVE: Most research on the symptomatic burden in bipolar disorder has included patients enrolled exclusively from tertiary centers, and only a few studies have analyzed factors related to it. We investigated the proportion of time and the proportion of visits with symptoms in a cohort of bipolar outpatients followed-up for 18 months, as well as the associated variables. METHODS: 296 DSM-IV-TR bipolar outpatients were included in a naturalistic longitudinal follow-up study, with quarterly assessment. Euthymia was defined by a Hamilton Depression Rating Scale score <7 and Young Mania Rating Scale score <5. Depressive episode, by a HDRS score of >17, hypomanic episode by a YMRS score of 10-20, and manic episode by a YMRS score >20. Sub-syndromal symptoms required scores of 7-17 in HDRS and 5-10 in YMRS. Based on a detailed recall of affective symptoms in the time between interviews, time in episode was also determined. RESULTS: Patients were symptomatic for one third of the follow-up, and also one third of the visits. They spent three times more days depressed than manic or hypomanic. More prior affective episodes were related both to more time symptomatic and more visits with symptoms. LIMITATIONS: Some of the data were collected retrospectively. Treatment was naturalistic. CONCLUSIONS: In a bipolar outpatient cohort from Spain, time with symptoms was shorter than previously found in tertiary care settings. In accordance with other longitudinal studies, those patients spent much more time depressed than manic.

Usefulness of the Spanish version of the mood disorder questionnaire for screening bipolar disorder in routine clinical practice in outpatients with major depression.

BACKGROUND: According to some studies, almost 40% of depressive patients - half of them previously undetected - are diagnosed of bipolar II disorder when systematically assessed for hypomania. Thus, instruments for bipolar disorder screening are needed. The Mood Disorder Questionnaire (MDQ) is a self-reported questionnaire validated in Spanish in stable patients with a previously known diagnosis. The purpose of this study is to evaluate in the daily clinical practice the usefulness of the Spanish version of the MDQ in depressive patients. METHODS: Patients (n = 87) meeting DSM-IV-TR criteria for a major depressive episode, not previously known as bipolar were included. The affective module of the Structured Clinical Interview (SCID) was used as gold standard. RESULTS: MDQ screened 24.1% of depressive patients as bipolar, vs. 12.6% according to SCID. For a cut-off point score of 7 positive answers, sensitivity was 72.7% (95% CI = 63.3 - 82.1) and specificity 82.9% (95% CI = 74.9-90.9). Likelihood ratio of positive and negative tests were 4,252 y 0,329 respectively. LIMITATIONS: The small sample size reduced the power of the study to 62%. CONCLUSION: Sensitivity and specificity of the MDQ were high for screening bipolar disorder in patients with major depression, and similar to the figures obtained in stable patients. This study confirms that MDQ is a useful instrument in the daily clinical assessment of depressive patients.

Clinical and psychosocial factors associated with the outcome of unipolar major depression: a one year prospective study.

BACKGROUND: The role of psychosocial and clinical variables in the prediction of major depression is controversial. In a previous paper, we obtained a one-year predictive multivariate model of non-remission for major depression, based on the presence of a personality disorder, a low self-esteem and a low satisfaction with social support. OBJECTIVES: To evaluate more in depth both personality disorders and psychosocial variables as predictors of outcome. METHODS: A prospective study on 57 consecutive outpatients with major depressive episodes were followed-up monthly during one year. Clinical and psychosocial variables were registered, including personality (DSM-IV criteria and IPDE structured interview), previous quality of life, self-esteem, social support and dyadic adjustment. Remission was defined as a HDS score less than 8. Univariate and multivariate (logistic regression) analyses were applied. RESULTS: 68% of the patients reached remission at 12 months. Personality disorder (diagnosed clinically but not according to IPDE), and previous quality of life were the variables more consistently associated to remission at 12 months. Among follow-up variables, remission at 3 months was strongly associated with remission. CONCLUSIONS: Our findings confirm the importance of the clinical diagnosis of personality disorder in the major depression outcome. However, more studies are needed to clarify the divergence between clinical and structured interview guided diagnosis. With the exception of quality of life, psychosocial variables had a weak and non consistent relationship with outcome.