Bipolar Disorder: Vieta E

Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Moller HJ, Kasper S. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · World J Biol Psychiatry. · Pubmed #19347775 No free full text.

Abstract: These updated guidelines are based on a first edition that was published in 2003, and have been edited and updated with the available scientific evidence until end of 2008. Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of acute mania in adults. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, from the clinical trial database clinicaltrials.gov, from recent proceedings of key conferences, and from various national and international treatment guidelines. Their scientific rigor was categorised into six levels of evidence (A-F). As these guidelines are intended for clinical use, the scientific evidence was finally asigned different grades of recommendation to ensure practicability.

Ghaemi SN, Bauer M, Cassidy F, Malhi GS, Mitchell P, Phelps J, Vieta E, Youngstrom E, Anonymous00020. · Bipolar Disorder Research Program, Department of Psychiatry, Emory University, Atlanta, GA 30322, USA. · Bipolar Disord. · Pubmed #18199230 No free full text.

Abstract: The Diagnostic Guidelines Task Force of the International Society for Bipolar Disorders (ISBD) presents in this document and this special issue a summary of the current nosological status of bipolar illness, a discussion of possible revisions to current DSM-IV and ICD-10 definitions, an examination of the relevant literature, explication of areas of consensus and dissensus, and proposed definitions that might guide clinicians in the most valid approach to diagnosis of these conditions given the current state of our knowledge.

Grunze H, Kasper S, Goodwin G, Bowden C, Baldwin D, Licht RW, Vieta E, Möller HJ, Anonymous00027. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #12582971 No free full text.

Abstract: Identical to the preceding guidelines of this series, these practice guidelines for the biological, mainly pharmacological treatment of acute bipolar mania were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of acute mania. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, from recent proceedings of key conferences, and from various national and international treatment guidelines. Their scientific rigor was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was finally not only graded, but has also been commented by the experts of the task force to ensure practicability. Key words: bipolar disorder, mania, acute treatment, evidence-based guidelines, pharmacotherapy, antipsychotics, mood stabiliser, electroconvulsive therapy.

Grunze H, Kasper S, Goodwin G, Bowden C, Baldwin D, Licht R, Vieta E, Möller HJ, Anonymous00265. · Department of Psychiatry, Ludwig-Maximilians-University, Nussbaumstrasse 7, 80336 Munich, Germany. · World J Biol Psychiatry. · Pubmed #12478876 No free full text.

Abstract: These practice guidelines for the biological, mainly pharmacological treatment of bipolar depression were developed by an international task force of the World Federation of Societies of Biological Psychiatry (WFSBP). Their purpose is to supply a systematic overview of all scientific evidence pertaining to the treatment of bipolar depression. The data used for these guidelines have been extracted from a MEDLINE and EMBASE search, and from recent proceedings of key conferences and various national and international treatment guidelines. Their scientific rigor was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was not only graded, but also commented on by the experts of the task force to ensure practicability.

Benabarre A, Castro P, Sánchez-Moreno J, Martinez-Arán A, Salamero M, Murru A, Franco C, Vieta E. · No affiliation provided · Actas Esp Psiquiatr. · Pubmed #19533426 links to  free full text

Abstract: Introduction. Our aim was to evaluate treatment safety, tolerability, efficacy and compliance of long-acting injectable risperidone (LAIR) as maintenance treatment in a bipolar and schizoaffective inpatients sample with torpid course due to poor compliance to oral therapy. Methods. 22 inpatients, 14 with a diagnosis of bipolar disorder and 8 with a diagnosis of schizoaffective disorder, were included in this study. They were treated with LAIR, 1 dose every 14 days, and were evaluated for 40 weeks with the Young Mania Rating Scale (YMRS), Hamilton Scale for Depression (HAM-D), UKU-Side Effect Rating Scale and Clinical Global Impression Severity of Illness scales (CGI). Results. Average YMRS scores were reduced significantly from 10.5 at baseline interview to 2.5 at week 40 (p < 0.001). HAM-D and UKU scales did not reach a statistically significant reduction. CGI-S scores were reduced from 3.8 at baseline to 1.5 at week 40 (p < 0.001). Conclusions. LAIR could be an effective maintenance therapy for bipolar and schizoaffective patients with poor compliance to oral treatment. Key words: Bipolar disorder. Schizoaffective disorder. Risperidone. Long-acting antipsychotic. Adherence. Actas Esp Psiquiatr 2008;37(3):143-147.

Vieta E. · No affiliation provided · World J Biol Psychiatry. · Pubmed #19347774 No free full text.

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Vieta E. · No affiliation provided · Acta Psychiatr Scand. · Pubmed #18855837 No free full text.

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Jaeger J, Vieta E. · No affiliation provided · Bipolar Disord. · Pubmed #17391343 No free full text.

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Tamayo J, Zarate C, Vieta E, Tohen M. · Departamento de Investigaciones Clínicas en Neurociencias de Eli Lilly & Co. Puerto Rico y Cuenca del Caribe. Cátedra de Psicofarmacología de la Universidad de Puerto Rico. · Actas Esp Psiquiatr. · Pubmed #16177951 links to  free full text

Abstract: Appropriate treatment of bipolar disorder has been the subject of debate since the first evidence of lithium's effectiveness in the treatment of mania, presented by Schou in 1954. A great deal has been written since then on the short and long-term safety and efficacy of the drugs used to control the various phases of this disorder. These medications have proven to be substantially different in this respect, for which reason their generic classification as mood stabilizers should be reevaluated.<p>This review draws on information about these differences, and proposes a new definition of these medications based on placebo-controlled, randomized, doubl e-blind studies: 1 ) antimanics for those with demonstrated efficacy in controlling manic episodes only; 2 ) partial stabilizers for those with demonstrated efficacy in controlling manic episodes and in preventing recurrence of mania, or those that are effective in controlling depressive episodes and preventing recurrence of depression, and 3 ) euthymics for this which, used as monotherapy, have proven to be effective in controlling manic, mixed, and depressive episodes and in preventing manic and depressive episodes.</p><p>In addition to an updated review of the pharmacotherapy of manic episodes, mixed episodes, rapid cyclers, depressive episodes, and prophylaxis of bipolar disorders, we also present the differences in safety and pharmacological characteristics of the drugs used in bipolar disorder.</p>

Rosa AR, Franco C, Torrent C, Comes M, Cruz N, Horga G, Benabarre A, Vieta E. · Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBER-SAM, Barcelona, Spain. · CNS Neurosci Ther. · Pubmed #19040553 No free full text.

Abstract: Ziprasidone was the fifth atypical antipsychotic approved by Food and Drug Administration (FDA) for use in bipolar mania and mixed episodes. This atypical antipsychotic has a unique profile, as it acts primarily through serotonergic and dopaminergic receptor antagonism, but also exerts effects as an inhibitor of norepinephrine reuptake. Moreover, one of the advantages of ziprasidone is its safety profile as it is not associated with clinically significant metabolic side effects and little or no effect on prolactin level or anticholinergic side effects. Most of the studies evaluating ziprasidone's efficacy and safety are short-term double-blind, placebo-controlled studies in acute mania and mixed episodes. In two of them, ziprasidone was associated to significant improvement in the primary measures assessed. However, an add-on study, lithium plus ziprasidone showed similar results than lithium monotherapy, although there was a significant advantage for the combination within the first week. In a more recent trial, ziprasidone was compared with placebo and haloperidol as monotherapies, again beating placebo. In that trial, ziprasidone appeared to be safer and better tolerated, although less likely efficacious than haloperidol. Particularly, subjects treated with ziprasidone were less likely to switch to depression. Despite the well-studied efficacy of ziprasidone in the first weeks of treatment, there are no controlled trials that evaluate the role and efficacy of ziprasidone in long-term treatment of bipolar disorder (BD). Overall, in the open-label extension studies, there was a global improvement at all visits compared with baseline scores. Furthermore, ziprasidone appears to offer some antidepressant effect in patients with major depressive episode and resistant to treatment, as demonstrated in add-on open-label studies with ziprasidone plus selective serotonin reuptake inhibitor (SSRI).

Fountoulakis KN, Vieta E. · 3rd Department of Psychiatry, Aristotle University of Thessaloniki, Greece. · Int J Neuropsychopharmacol. · Pubmed #18752718 No free full text.

Abstract: This paper is a systematic review of the available data concerning the treatment of bipolar disorder: a systematic Medline search concerning treatment guidelines and clinical trials. The search for treatment guidelines returned 583 articles and 913 papers for RCTs. The search was last performed on 1 March 2008. An additional search included repositories of clinical trials and previous systematic reviews in order to trace especially older trials. The literature suggests that lithium is useful during the acute manic and the maintenance phase. Both first- and second-generation antipsychotics are efficacious in the treatment of acute mania. Quetiapine and the olanzapine-fluoxetine combination are also effective for treating bipolar depression, while olanzapine, quetiapine and aripiprazole are effective during the maintenance phase. Anticonvulsants, particularly valproate and carbamazepine have antimanic properties, whereas lamotrigine may be preferably effective in the treatment of depression but not mania. Antidepressants should always be used in combination with an antimanic agent because they were reported to induce switching to mania or hypomania, mixed episodes, and rapid cycling when given as monotherapy. The best evidence-based psychosocial interventions for bipolar disorder are group- and family-focused psychoeducation. Electroconvulsive therapy is an option for refractory patients. Although a variety of treatment options for bipolar disorder is currently available, their effectiveness is far from satisfactory, especially against bipolar depression and maintenance. Combination therapy may improve treatment outcome but it also carries the burden of more side-effects. Further research as well as the development of better guidelines and algorithms for step-by-step rational treatment are necessary.

Vieta E, Sanchez-Moreno J. · Bipolar Disorders Program, University of Barcelona, Hospital Clinic, IDIBAPS, CIBER-SAM, Barcelona, Catalonia, Spain. · Dialogues Clin Neurosci. · Pubmed #18689287 No free full text.

Abstract: The treatment of mania starts with a correct diagnosis and elementary measures to prevent risks for the patient, relatives, and others. Sometimes, compulsory admission and treatment may be required for a few days. Patients with psychotic or mixed mania may be more difficult to treat. At the present time, there is solid evidence supporting the use of lithium, the anticonvulsants valproate and carbamazepine, and the antipsychotics chlorpromazine, haloperidol, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, and asenapine in acute mania, and some evidence supporting the use of clozapine or electroconvulsive therapy in treatment-refractory cases. However, in clinical practice, combination therapy is the rule rather than the exception. The treatment of acute mania deserves a long-term view, and the evidence base for some treatments may be stronger than for others. When taking decisions about treatment, tolerability should also be a major concern, as differences in safety and tolerability may exceed differences in efficacy for most compounds. Psychoeducation of patients and caregivers is a powerful tool that should be used in combination with medication for optimal long-term outcome. Functional recovery should be the ultimate goal.

Martinez-Arán A, Vieta E, Chengappa KN, Gershon S, Mullen J, Paulsson B. · Bipolar Disorders Program, IDIBAPS, CIBER-SAM, Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, Barcelona, Spain. · Bipolar Disord. · Pubmed #18657241 No free full text.

Abstract: OBJECTIVE: Newer outcome measures and statistical reporting that better translate efficacy data to evidence-based psychiatric care are needed when evaluating clinical trials for bipolar disorder. Using efficacy studies as illustrations, the authors review and recommend changes in the reporting of traditional clinical outcomes both in the acute and maintenance phases of bipolar disorder. METHODS: Definitions of response, remission, relapse, recovery, and recurrence are reviewed and recommendations for change are made. These suggestions include reporting the numbers needed to treat or harm (NNT or NNH), and a ratio of the two, likelihood of help or harm (LHH), as an important element of the effect size (ES). Moreover, models of prediction that conduct sensitivity or specificity analyses and utilize decision trees to help predict positive and negative outcomes of interest (for instance, excessive weight gain, or time to remission) using positive or negative predictive values (PPV or NPV) are reviewed for potential value to clinicians. Finally, functional and cognitive assessments are recommended for maintenance studies of bipolar disorder. RESULTS: The examples provided in this manuscript underscore that reporting the NNT or NNH, or alternative effect sizes, or using PPV or NPV may be of particular value to clinicians. Such reports are likely to help translate efficacy-driven clinical data to information that will more readily guide clinicians on the benefits and risks of specific interventions in bipolar disorder. CONCLUSIONS: The authors opine that reporting these newer outcomes, such as NNT or NNH, area under the receiver operating curve (AUC), or PPV or NPV will help translate the results of clinical trials into a language that is more readily understood by clinicians. Moreover, assessing and evaluating functional and cognitive outcomes will not only inform clinicians about potential differences among therapeutic options, but likely will make it easier to communicate such differences to persons with bipolar illness or to their families. Finally, we hope such scientific and research efforts will translate to optimism for recovery-based outcomes in persons with bipolar disorder.

Balanzá-Martínez V, Rubio C, Selva-Vera G, Martinez-Aran A, Sánchez-Moreno J, Salazar-Fraile J, Vieta E, Tabarés-Seisdedos R. · Teaching Unit of Psychiatry and Psychological Medicine, Department of Medicine, CIBER-SAM, University of Valencia, Spain. · Neurosci Biobehav Rev. · Pubmed #18582942 No free full text.

Abstract: BACKGROUND: There is growing interest to research neurocognition as a putative endophenotype for subjects with bipolar disorders (BD). The authors sought to review the available literature focused on relatives of subjects with bipolar disorder (BD-Rels) and identify suitable cognitive candidates to endophenotypes or endophenocognitypes. METHOD: A systematic review was conducted in Medline, EMBASE and PsycINFO databases (1980-July 2007), supplemented with a manual search of reference lists. RESULTS: Twenty-three cross-sectional papers of discordant twins (4 studies), genetic high-risk subjects (7), and different BD-Rel groups (12) met the inclusion criteria and evaluated 532 BD-Rels. Impairments on the broad domain of verbal learning/memory were found in 6 out of 11 studies (54%), as well as in 3 of 9 reports (33%) of working memory. Moreover, BD-Rels showed deficits in visual-spatial learning and memory (1/6 reports; 17%), alternating attention (1/8; 12.5%), psychomotor speed (2/10; 20%), and abstraction/cognitive flexibility, sustained attention and selective attention (2/8 each; 25%). Scores of general intelligence were lower than those of controls in 2/16 (12.5%) reports, but fell well within the average range in all studies. No study that assessed immediate memory or verbal fluency (6 each) reported impairments in BD-Rels. Finally, language, social cognition, and motor and planning skills are neglected areas of research. CONCLUSIONS: Overall, the neurocognitive profile in BD-Rels is still unclear, and the evidence in support of the presence of cognitive deficits seems quite sparse. Verbal learning/memory and verbal working memory seem to be the most suitable endophenocognitypes for BD. Conversely, healthy family members would have an intact performance on immediate memory, verbal fluency, and probably on general intelligence. The possibility that BD-Rels show less cognitive efficiency compared to healthy controls also on other functions must be addressed by future studies with larger samples, comprehensive neuropsychological assessments, and, ideally, longitudinal designs.

Goodwin GM, Anderson I, Arango C, Bowden CL, Henry C, Mitchell PB, Nolen WA, Vieta E, Wittchen HU. · University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK. · Eur Neuropsychopharmacol. · Pubmed #18501566 No free full text.

Abstract: DIAGNOSIS AND EPIDEMIOLOGY: DSM-IV, specifically its text revision DSM-IV-TR, remains the preferred diagnostic system. When employed in general population samples, prevalence estimates of bipolar disorder are relatively consistent across studies in Europe and USA. In community studies, first onset of bipolar mood disorder is usually in the mid-teenage years and twenties, and the occurrence of a major depressive episode or hypomania is usually its first manifestation. Since reliable criteria for delineating unipolar (UP) and bipolar (BI) depression cross-sectionally are currently lacking, there is a longitudinal risk - probably over 10% - that initial UP patients ultimately turn out as BP in the longer run. Its early onset implies a severe potential burden of disease in terms of impaired social and neuropsychological development, most of which is attributable to depression. BIPOLAR DEPRESSION IN CHILDREN: Bipolar I disorder is rare in prepubertal children, when defined according to unmodified DSM-IV-TR criteria. A broad diagnosis of bipolar disorder risks confounding with other childhood psychopathology and has less predictive value for bipolar disorder in adulthood than the conservative definition. Nevertheless, empirical studies of drug and other treatments and longitudinal studies to assess validity of the broadly defined phenotype in children and adolescents are desirable, rather than extrapolation from adult bipolar practice. The need for an increased capacity to conduct reliable trials in children and adolescents is a challenge to Europe, whose healthcare system should allow greater participation and collaboration than other regions, via clinical networks. ECNP will aspire to facilitate such developments. BIPOLAR DEPRESSION IN ADULTS - UNIPOLAR/BIPOLAR CONTRAST: Despite some differences in symptom profiles and severity measures, a cross-sectional categorical distinction between bipolar (BP) and unipolar (UP) depression is currently impossible. For regulatory purposes, a major depressive episode, meeting DSM-IV-TR criteria, remains the same diagnosis, irrespective of the overall course of the disorder. However, in refining diagnosis in future studies and DSM-V, a probabilistical approach to the UP/BP distinction is more likely to be informative as recommended by the International Society for Bipolar Disorders (ISBD). Anxiety is a commonly present, often at syndromal levels, in bipolar populations. Thus, RCT inclusion criteria for trials not targeting anxiety, should accept co-morbid anxiety disorders as part of the history and even current anxiety symptoms, where these are not dominating the mental state at recruitment to a study. Rapid cycling patients defined as those suffering from 4 or more episodes per year, may also be recruited into trials of bipolar depression without impairing assay sensitivity. Illness severity critically affects assay sensitivity. The minimum scores for entry into a bipolar depression trials should be >20 on HAM-D (17 item scale). However, efficacy is best detected in patients with HAM-D >24 at baseline. THE USE OF RATING SCALES IN BIPOLAR DEPRESSION: There is some dissatisfaction with the HAM-D or MADRS as the preferred primary outcome for trials, although they probably capture global severity adequately. Secondary measures to capture so-called atypical symptoms (such as hypersomnia or hyperphagia), or specific psychopathology more common in bipolar participants (such as lability of mood), could be informative as secondary measures. TREATMENT STUDIES IN BIPOLAR DEPRESSION: Monotherapy trials against placebo remain the gold-standard design for determining efficacy in bipolar depression. The confounding effects of co-medication are emerging from the literature on antidepressant studies in bipolar depression, often conducted in combination with antimanic agents to avoid possible switch to mood elevation. Three arm trials, including the compound to be tested, placebo, and a standard comparator, are generally preferred in order to ensure assay sensitivity and a better picture of benefit-risk ratio. However, in the absence of any gold-standard, two-arm trials may be enough. If efficacy happens to be proven as monotherapy, new compounds may be tested in adjunctive-medication placebo-controlled designs. Younger adults, without an established need for long-term medication, may be particularly suitable for clinical trials requiring placebo controls. The conversion rate of initial UP depression, converting to become BP in the long run is estimated to be 10%. Switch to mania or hypomania may be the consequence of active treatment for bipolar depression. Some medicines such as the tricyclic antidepressants and venlafaxine may be more likely to provoke switch than others, but this increased rate of switch may not be seen until about 10 weeks of treatment. Twelve week trials against placebo are necessary to determine the risk of switch and to establish continuing effects. Careful assessment at 6-8 weeks is required to ensure that patients who are failing to respond do not continue in a study for unacceptable periods of time. To capture a switch event, studies should include scales to define the phenomenology of the event (e.g. hypomania or mania) and its severity. These may be best applied shortly after the clinical decision that switch is occurring. Long-term treatment is commonly required in bipolar disorder. Trials to detect maintenance of effect or continued response in bipolar depression should follow a 'relapse prevention' design: i.e. patients are treated in an index episode with the medicine of interest and then randomized to either continue the active treatment or placebo. However, acute withdrawal of active medication after treatment response might artificially enhance effect size due to active drug withdrawal effects. A short taper is usually desirable. Longer periods of stabilisation are also desirable for up to 3 months: protocol compliance may then be difficult to achieve in practice and so will certainly make studies more difficult and expensive to conduct. The addition of a medicine to other agents during or after the resolution of a depressive or manic episode, and its subsequent investigation as monotherapy against placebo to prevent further relapse (as in the lamotrigine maintenance trials) is clinically informative. Assay sensitivity and patient acceptability are enhanced if the outcome in long-term studies is 'time to intervention for a new episode' for discontinuation designs.

Torrent C, Amann B, Sánchez-Moreno J, Colom F, Reinares M, Comes M, Rosa AR, Scott J, Vieta E. · Bipolar Disorders Program, Clinical Institute of Neuroscience, University Hospital Clinic, University of Barcelona, IDIBAPS, CIBER-SAM, Barcelona, Spain. · Acta Psychiatr Scand. · Pubmed #18498432 No free full text.

Abstract: OBJECTIVE: The aim of this paper was to review the association of most commonly used psychopharmacological drugs with weight gain in bipolar disorder. METHOD: Information was retrieved from a PubMed/Medline literature search reviewing weight gain in pharmacological studies in bipolar disorder. RESULTS: Obesity and overweight in bipolar disorder are partly related to prescribed drugs with a strong effect of clozapine and olanzapine. Lesser but still relevant weight gain is caused by quetiapine, risperidone, lithium, valproate, gabapentin and by some antidepressants. Ziprasidone, aripiprazole, carbamazepine and lamotrigine do not seem to cause significant overweight. CONCLUSION: Careful monitoring of weight changes in patients before and after drug prescription should be implemented in the clinical routine and drugs which potentially cause weight gain should be avoided in overweight patients with bipolar disorder. Furthermore, eating habits and daily activities should be targeted as they may also have a significant impact on overall health and weight-related issues.

Vieta E, Franco C. · Programa de Trastornos Bipolares, Instituto Clínico de Neurociencias, Hospital Clínic, Universitat de Barcelona, IDIBAPS, CIBER-SAM, Barcelona. · Actas Esp Psiquiatr. · Pubmed #18478456 links to  free full text

Abstract: Aripiprazole is a dopamine partial agonist antipsychotic drug that has just been approved in Europe for its use in the treatment of acute mania and for the prevention of manic episodes in bipolar disorder. Its efficacy in mania is superior to that of placebo, both as monotherapy and as adjunctive therapy, and comparable to that of haloperidol and lithium. From the safety perspective it is remarkable that it is not highly sedative and does not impair the metabolic parameters. The advantages of a non-sedative and metabolically neutral antimanic drug are particularly relevant in the long-term, due to their impact on cognition and quality of life. The experience on its use in routine clinical practice indicates that in order to avoid phenomena such as activation, abrupt worsening or akathisia, it is recommendable to start treatment with low doses and to increase them progressively, especially in those patients who are already receiving other drugs; moreover, it is advisable not to stop abruptly any ongoing treatment, unless there is an emergency, to transiently prescribe a concomitant benzodiazepine, and to maintain the dose that proved efficacious during the short term treatment during maintenance therapy.

Daban C, Martinez-Aran A, Cruz N, Vieta E. · Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBER-SAM, Barcelona, Spain. · J Affect Disord. · Pubmed #18374988 No free full text.

Abstract: OBJECTIVE: The main objective of this review of the literature was to evaluate the safety and efficacy of Vagus Nerve Stimulation (VNS) in treatment-resistant depression (TRD) by means of systematic review and meta-analysis. METHODS: A systematic review of the literature was made using the major databases (Medline, Psychological Abstracts, Current Contents), beginning in January 2000 and ending in September 2007. Ninety-eight references were found, but only 18 add-on studies met the required quality criteria and were included in this review. Only one double-blind, randomized study was available and therefore a meta-analysis was not feasible. RESULTS: In a majority of the preliminary open studies selected for this review, VNS was associated with a significant reduction of the depressive symptoms (primary outcome: Hamilton Depression Rating Scale, HDRS) in the short and long term. Unfortunately, the only double-blind study gave rather inconclusive results. Generally, VNS is reported to be a safe and feasible procedure, despite its invasive nature. CONCLUSIONS: VNS seems to be an interesting new approach to treating TRD. However, despite the promising results reported mainly in open studies, further clinical trials are needed to confirm its efficacy in major depression. Moreover, studies on its mechanism of action and cost-effectiveness are also required to better understand and develop VNS therapy for affective disorder.

Kapczinski F, Vieta E, Andreazza AC, Frey BN, Gomes FA, Tramontina J, Kauer-Sant'anna M, Grassi-Oliveira R, Post RM. · Bipolar Disorders Program and Laboratory of Molecular Psychiatry, Hospital de Clinicas de Porto Alegre, Ramiro Barcelos 2350, 90035-000, Porto Alegre, RS, Brazil. · Neurosci Biobehav Rev. · Pubmed #18199480 No free full text.

Abstract: Current literature on the effects of chronic stress in general health converges to the concept of allostatic load (AL). AL is the bodily 'wear and tear' that emerges with sustained allostatic states. In the field of bipolar disorder (BD), AL offers an important clue as to why patients who undergo recurrent mood episodes are clinically perceived as less resilient. In addition, AL helps explaining the cumulative disruptive health effects of intermittent episodes and stressors. Stress- and episode-induced changes in brain regions involved in the emotional circuitry may lead to dysfunctional processing of information, which would render BD patients more vulnerable to subsequent environmental stressors, episodes, and drugs of abuse. Mood stabilizing agents exert opposite effects than chronic stress in neurons, increasing neuroprotective factors what may help to quench the cycle of affective episode recurrence and neural and bodily deterioration. Therefore, AL provides an explanatory link to apparently unrelated findings such as cognitive impairment and higher rates of physical comorbidity and mortality that are observed in the course of BD and further highlight the importance of effective long-term prophylaxis.

Vieta E, Suppes T. · Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBER-SAM, Barcelona, Spain. · Bipolar Disord. · Pubmed #18199235 No free full text.

Abstract: OBJECTIVE: As a commitment to the International Society for Bipolar Disorders (ISBD), a Task Force was developed to investigate the diagnostic value of bipolar II disorder. METHODS: Task Force members worked jointly reviewing all relevant literature (original articles, reviews, letters, book chapters and congress presentations) that included 'bipolar II disorder' and/or 'hypomania' as key words. RESULTS: Bipolar II disorder appears to be a reasonably valid and reliable diagnostic category yet often underdiagnosed or misdiagnosed as unipolar disorder or personality disorder. Moreover, it is officially recognized as a mental disorder in DSM-IV-TR but not in ICD-10, and many clinicians still regard it as a milder form of manic-depressive illness, despite data supporting high morbidity and mortality rates. In fact, bipolar II may be the most prevalent bipolar phenotype, although current diagnostic boundaries are seen as quite restrictive concerning the required duration for hypomania (4 days), the exclusion of hypomanic episodes potentially triggered by antidepressants and other substances, and the negligence of hypomanic mixed states. The course of bipolar II disorder is characterized by depressive predominant polarity, and its treatment is still controversial and poorly evidence-based. CONCLUSIONS: Bipolar II disorder is supported as a distinct category within mood disorders, but the definition and boundaries deserve a greater clarification in the DSM-V and ICD-11.

Valentí M, Benabarre A, García-Amador M, Molina O, Bernardo M, Vieta E. · Bipolar Disorders Program, Institute of Clinical Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBER-SAM, Villarroel 170/Rossello 140, 08036 Barcelona, Catalonia, Spain. · Eur Psychiatry. · Pubmed #18191551 No free full text.

Abstract: INTRODUCTION: Mixed bipolar states are not infrequent and may be extremely difficult to treat. Lithium, anticonvulsants including valproate and carbamazepine, and antipsychotics such as olanzapine, ziprasidone, and aripiprazole have been reported to be at least partially effective in controlled clinical trials, but many patients do not respond to pharmacological approaches. Electroconvulsive therapy has been tested to be efficacious for the treatment of both manic and depressive episodes, but much less evidence is available with regards to mixed states. The aim of the review was to report the available evidence for the use of electroconvulsive therapy in mixed bipolar states. METHODS: A systematic review of the literature on treatment of mixed states, focused on electroconvulsive therapy, was made, beginning in August 1992 and ending in March 2007. The key words were "electroconvulsive therapy" and "mixed bipolar". RESULTS: Only three studies met the required quality criteria and were included. This literature suggests that ECT is an effective, safe, and probably underutilized treatment of mixed states. Recent technical developments have made ECT more friendly, tolerable, and safe. Potential alternatives, such as vagus nerve stimulation, deep brain stimulation, or transcranial stimulation, are still far to be proved as effective as ECT.

Colom F, Vieta E. · Bipolar Disorders Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain. · Psychother Psychosom. · Pubmed #17700048 No free full text.

Abstract: INTRODUCTION: Cognitive aspects of hypomania have been historically neglected. Although they do not have an etiological role, they may be essential to understand factors underlying the hypomanic ascent in bipolar disorders and constitute key modulators of the course of illness. METHODS: We have performed a critical review of the existing literature on the role of cognition during hypomania, considering outputs coming from very different fields of knowledge. RESULTS: There is a nuclear cognitive change occurring in most hypomanic phases that we have defined as 'anastrophic' thinking. This key cognitive procedure has several implications--going from social sciences and philosophy to basic sciences. CONCLUSIONS: Hypomania has received certain attention from cognitive theorists. Unfortunately, this attention has not been translated into a cognitive model that is as robust as the one seen in depression. The inclusion of certain psychological aspects in models of hypomania should give rise, as occurred with depression, to an increased emphasis on psychoeducation and cognitive modification of behavioral patterns in the management of this disorder with combined psychological and pharmacological tools.

Popova E, Leighton C, Bernabarre A, Bernardo M, Vieta E. · Clinical Institute of Neuroscience, Hospital Clìnic, University of Barcelona, IDIBAPS, Barcelona, Spain. · Expert Rev Neurother. · Pubmed #17563245 No free full text.

Abstract: Oxcarbazepine is an antiepileptic drug that has been approved by the US FDA and is indicated for use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults and children aged over 4 years. The aim of this report is to investigate the results of clinical trials in order to ascertain the efficacy and safety of oxcarbazepine for use in bipolar disorder and schizoaffective disorder. Oxcarbazepine is a keto-congener of carbamazepine with fewer side effects and drug interactions. Orally administrated oxcarbazepine is rapidly and completely absorbed and has a half-life of 9 h. Currently, there is a lack of controlled clinical trials studying the use of oxcarbazepine. In light of controlled and open-label prospective studies, it may be useful for manic symptoms in the treatment of bipolar and schizoaffective patients. Case reports, retrospective and prospective studies suggest that oxcarbazepine might have prophylactic efficacy and long-term benefit for these patients. In addition, owing to its lower propensity for drug interactions and side effects, it may be useful in the treatment of refractory patients with bipolar and schizoaffective disorder. However, most of the trials have relevant methodological shortcomings. The side-effect profile of oxcarbazepine is similar to carbamazepine, but the severity of these effects appears to be slightly less. The symptoms that are most frequently associated with the use of oxcarbazepine are asthenia, headache, dizziness, somnolence, nausea, diplopia and skin rash. Isolated cases of hyponatremic coma have been reported, thus electrolyte abnormalities should be closely monitored. Oxcarbazepine is now a generic drug, but the metabolite licarbazepine and other related compounds, such as eslicarbazepine, are currently being studied under controlled conditions and might become useful therapies for bipolar and schizoaffective disorder in the future.

Phillips ML, Vieta E. · Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh, PA, USA. · Schizophr Bull. · Pubmed #17562698 links to  free full text

Abstract: Bipolar disorder is one of the most debilitating and common illnesses worldwide. Individuals with bipolar disorder frequently present to clinical services when depressed but are often misdiagnosed with unipolar depression, leading to inadequate treatment and poor outcome. Increased accuracy in diagnosing bipolar disorder, especially during depression, is therefore a key long-term goal to improve the mental health of individuals with the disorder. The attainment of this goal can be facilitated by identifying biomarkers reflecting pathophysiologic processes in bipolar disorder, namely impaired emotion regulation, impaired attention, and distractibility, which persist during depression and remission and are not common to unipolar depression. In this critical review, we examine the feasibility of identifying biomarker of bipolar disorder by discussing existing findings regarding functional abnormalities in neural systems underlying emotion processing (amygdala centered), working memory, and attention (dorsolateral prefrontal cortex centered) that persist through bipolar depression and remission and are bipolar specific rather than common to unipolar depression. We then focus on future research goals relating to major clinical problems in bipolar disorder, including, the identification of biomarkers allowing detection of individuals at risk of subsequent development of the disorder. Bipolar disorder is a common, debilitating, and potentially fatal disorder. Current and future research in bipolar disorder should focus on identification of disorder biomarkers to improve diagnostic accuracy and the mental heath of those with the disorder.

Vieta E, Phillips ML. · Bipolar Disorders Program, Institute of Neuroscience, University of Barcelona Hospital Clinic, Barcelona, Spain. · Schizophr Bull. · Pubmed #17562693 links to  free full text

Abstract: The development of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and International Classification of Diseases, Eleventh Edition, deserves a significant conceptual step forward. There is a clear need to improve and refine the current diagnostic criteria, but also to introduce dimensions, perhaps not as an alternative but rather as a useful complement to categorical diagnosis. Laboratory, family, and treatment response data should also be systematically included in the diagnostic assessment when available. We have critically reviewed the content, concurrent, discriminant, and predictive validity of bipolar disorder, and to overcome the validity problems of the current classifications of mental disorders, we propose a modular system which may integrate categorical and dimensional issues, laboratory data, associated nonpsychiatric medical conditions, psychological assessment, and social issues in a comprehensive and nevertheless practical approach.