Progress in research at the cibersam's Affective disorders programme of the University of Barcelona Hospital Clinic.

The affective disorders programme at the University of Barcelona Hospital Clinic involves two separate subgroups according to their research target: the Unipolar Depression subgroup and the Barcelona Bipolar Disorders Programme. Both are part of the Spanish "Centro de Investigación Biomédica En Red en Salud Mental" (CIBERSAM), which is a Virtual Center of Network Research in Mental Health and Psychiatry, which has gathered the best research groups in Psychiatry and related disciplines in Spain. The Clinic-Affective Disorders research group has focused on the neurobiology (genetics, biomarkers, neuropsychology, neuroimaging), epidemiology (clinical subtypes, comorbidity, psychometric assessment, functionality), and treatment of bipolar and unipolar affective disorders (including pharmacological, biophysical, and psychosocial strategies). It has an outstanding and long tradition of collaborative research with national and international groups, and publishes over 60 original articles per year based on research findings, many of which have had significant impact on clinical practice

Individualizing treatment for patients with schizoaffective disorder

Compelling diagnostic definitions and evidence-based treatment recommendations for schizoaffective disorder are lacking, but clinicians can still develop an effective, individualized treatment regimen for patients with this condition. The steps necessary to help patients with schizoaffective disorder reach and maintain remission are to confirm the diagnosis, evaluate the patient's predictors of outcome, be aware of the available pharmacotherapeutic options and prescribe appropriate medications, and implement psychotherapy when patients achieve remission. In this brief activity, these essential steps are discussed and treatment recommendations are offered

Class effect of pharmacotherapy in bipolar disorder: fact or misbelief?

BACKGROUND: Anecdotal reports suggests that most clinicians treat medications as belonging to a class with regard to all therapeutic indications; this means that the whole 'class' of drugs is considered to possesses a specific therapeutic action. The present article explores the possible existence of a true 'class effect' for agents available for the treatment of bipolar disorder. METHODS: We reviewed the available treatment data from randomized controlled trials (RCTs) and explored 16 'agent class'/'treatment issue' cases for bipolar disorder. Four classes of agents were examined: first-generation antipsychotics (FGAs), second-generation antipsychotics (SGAs), antiepileptics and antidepressants, with respect to their efficacy on four treatment issues of bipolar disorder (BD) (acute mania, acute bipolar depression, maintenance against mania, maintenance against depression). RESULTS: From the 16 'agent class'/' treatment issue' cases, only 3 possible class effects were detected, and they all concerned acute mania and antipsychotics. Four effect cases have not been adequately studied (FGAs against acute bipolar depression and in maintenance protection from depression, and antidepressants against acute mania and protection from mania) and they all concern treatment cases with a high risk of switching to the opposite pole, thus research in these areas is poor. There is no 'class effect' at all concerning antiepileptics. CONCLUSIONS: The available data suggest that a 'class effect' is the exception rather than the rule in the treatment of BD. However, the possible presence of a 'class effect' concept discourages clinicians from continued scientific training and reading. Focused educational intervention might be necessary to change this attitude

Factors modifying drug and placebo responses in randomized trials for bipolar mania

Factors modifying drug and placebo responses in randomized trials for bipolar mania. Yildiz A, Vieta E, Tohen M, Baldessarini RJ. Source Department of Psychiatry, Dokuz Eylül University, Izmir, Turkey. [email protected] Abstract Randomized placebo-controlled trials (RCTs) are standard for assessing efficacy and safety of treatments. We pursued preliminary indications that some factors are associated differentially with responses to placebo or drugs in RCTs for bipolar mania. We meta-analysed data from RCTs to assess influences of study-site count, subjects' age, sex distribution, diagnostic subgroups, clinical features, trial-completion rates, and publication year on mean difference (MD) in mania ratings between intake and final assessments. In 38 RCTs involving 3812 placebo-treated and 6988 drug-treated patients, symptomatic improvement was similar in placebo arms of trials of effective (6.77, 95% CI 5.77-7.76) and ineffective (7.61, 95% CI 5.47-8.75) drugs. Lesser placebo responses (MD) and greater drug-placebo differences (Hedges' g) were associated with fewer study sites, younger patients' age, and male sex. More patients with initial psychotic features and more trial completion in drug arms were associated with greater drug-associated improvement (MD) and drug-placebo contrast (Hedges' g), whereas more mixed-state diagnoses decreased both measures. Identifying modifying factors can support more efficient and cost-effective designs of therapeutic trials. In trials for mania, fewer sites may limit placebo response and enhance drug-placebo contrasts

Towards a clinical staging for bipolar disorder: defining patient subtypes based on functional outcome.

BACKGROUND: The functional outcome of Bipolar Disorder (BD) is highly variable. This variability has been attributed to multiple demographic, clinical and cognitive factors. The critical next step is to identify combinations of predictors that can be used to specify prognostic subtypes, thus providing a basis for a staging classification in BD. METHODS: Latent Class Analysis was applied to multiple predictors of functional outcome in a sample of 106 remitted adults with BD. RESULTS: We identified two subtypes of patients presenting "good" (n=50; 47.6%) and "poor" (n=56; 52.4%) outcome. Episode density, level of residual depressive symptoms, estimated verbal intelligence and inhibitory control emerged as the most significant predictors of subtype membership at the p<0.05 level. Their odds ratio (OR) and confidence interval (CI) with reference to the "good" outcome group were: episode density (OR=4.622, CI 1.592-13.418), level of residual depressive symptoms (OR=1.543, CI 1.210-1.969), estimated verbal intelligence (OR=0.969; CI 0.945-0.995), and inhibitory control (OR=0.771, CI 0.656-0.907). Age, age of onset and duration of illness were comparable between prognostic groups. LIMITATIONS: The longitudinal stability or evolution of the subtypes was not tested. CONCLUSIONS: Our findings provide the first empirically derived staging classification of BD based on two underlying dimensions, one for illness severity and another for cognitive function. This approach can be further developed by expanding the dimensions included and testing the reproducibility and prospective prognostic value of the emerging classes. Developing a disease staging system for BD will allow individualised treatment planning for patients and selection of more homogeneous patient groups for research purposes

Rationale and design of the PLACID study: a randomised trial comparing the efficacy and safety of inhaled loxapine versus IM aripiprazole in acutely agitated patients with schizophrenia or bipolar disorder

Background: The management of acute agitation manifesting in patients with schizophrenia or bipolar disorder requires swift pharmacological intervention to provide rapid symptomatic relief and prevent escalation to aggression and violence. Antipsychotic medications are widely used in this setting and the availability of an inhaled formulation with deep lung absorption of the antipsychotic loxapine has the potential to deliver a faster onset of therapeutic effect than the available intramuscular formulations of antipsychotics. Methods: The efficacy of inhaled loxapine and the alternative antipsychotic aripiprazole delivered via intramuscular (IM) injection will be compared in the Phase IIIb PLACID study. Adults (18-65 years) with a confirmed diagnosis of schizophrenia or bipolar I disorder presenting with acute agitation will be randomly assigned to open-label treatment in a 1:1 ratio. Clinical evaluation will be conducted by raters blinded to treatment assignment. The primary efficacy endpoint is time to response (defined as a Clinical Global Impression of Improvement [CGI-I] score of 1 [very much improved] or 2 [much improved]). Secondary endpoints will include the percentage of responders at different time points after dosing; the proportion of patients who receive 1 or 2 doses of study drug; time to second dose; time to rescue medication; satisfaction with study drug (evaluated using Item 14 of the Treatment Satisfaction Questionnaire for Medication); and safety and tolerability. Approximately 360 patients will be recruited with an interim analysis conducted once 180 patients have completed the study to decide whether to stop for futility or continue with or without an increase in the sample size up to additional 288 patients. Discussion: The PLACID trial will assess the efficacy and safety of inhaled loxapine with deep lung absorption compared with the IM antipsychotic, aripiprazole, in acutely agitated patients with schizophrenia or bipolar disorder. In the event that the median time to response of inhaled loxapine is significantly shorter than that of the intramuscular aripiprazole, the PLACID study has the potential to support the inhaled antipsychotic therapy as the standard of care in this setting

Antipsychotic switching in bipolar disorders: a systematic review.

With the increasingly widespread use of antipsychotics in bipolar disorder (BD), switching among these agents and between antipsychotics and mood stabilizers has become more common, in particular, since the introduction of the novel atypical antipsychotics with mood stabilizer properties. This systematic review aims to provide a comprehensive update of the current literature in BD about the switching of antipsychotics, among them and between them and mood stabilizers, in acute and maintenance treatment. We conducted a comprehensive, computerized literature search using terms related to antipsychotic switching in BD in the PubMed/Medline, PsycINFO, CINAHL database; the Cochrane Library and; the Clinicaltrials.gov web up to January 9th, 2013 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search returned 4160 articles. After excluding duplications, reviews, case reports and studies that did not fulfil the selection criteria, 8 studies were included. Not only have few articles on antipsychotic switching been published but also recruitment in most studies included mixed samples of patients. In general, antipsychotic switching, regardless of the route of drug administration, was well tolerated and no interference was shown in antipsychotic effectiveness during the interchange of drugs. Metabolic improvement was perceived when the switch involved antipsychotics with a low metabolic risk profile. The evidence-base for antipsychotic switching in BD is scant, and little controlled data is available. Switch from quetiapine to lithium and from risperidone to olanzapine has proven successful. Switching to antipsychotics with low metabolic risk had some positive impact on several safety measures. In stabilized patients, the plateau cross-taper switch may be preferred. PsycINFO, CINAHL database; the Cochrane Library and; the Clinicaltrials.gov web up to January 9th, 2013 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search returned 4160 articles. After excluding duplications, reviews, case reports and studies that did not fulfil the selection criteria, 8 studies were included. Not only have few articles on antipsychotic switching been published but also recruitment in most studies included mixed samples of patients. In general, antipsychotic switching, regardless of the route of drug administration, was well tolerated and no interference was shown in antipsychotic effectiveness during the interchange of drugs. Metabolic improvement was perceived when the switch involved antipsychotics with a low metabolic risk profile. The evidence-base for antipsychotic switching in BD is scant, and little controlled data is available. Switch from quetiapine to lithium and from risperidone to olanzapine has proven successful. Switching to antipsychotics with low metabolic risk had some positive impact on several safety measures. In stabilized patients, the plateau cross-taper switch may be preferred