Emanuel Severus

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the acute and continuation treatment of unipolar depressive disorders

Abstract Objectives. This 2013 update of the practice guidelines for the biological treatment of unipolar depressive disorders was developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal has been to systematically review all available evidence pertaining to the treatment of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. The guidelines are intended for use by all physicians seeing and treating patients with these conditions. Methods. The 2013 update was conducted by a systematic update literature search and appraisal. All recommendations were approved by the Guidelines Task Force. Results. This first part of the guidelines (Part 1) covers disease definition, classification, epidemiology, and course of unipolar depressive disorders, as well as the management of the acute and continuation phase treatment. It is primarily concerned with the biological treatment (including antidepressants, other psychopharmacological medications, electroconvulsive therapy, light therapy, adjunctive and novel therapeutic strategies) of adults. Conclusions. To date, there is a variety of evidence-based antidepressant treatment options available. Nevertheless there is still a substantial proportion of patients not achieving full remission. In addition, somatic and psychiatric comorbidities and other special circumstances need to be more thoroughly investigated. Therefore, further high-quality informative randomized controlled trials are urgently needed.

Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on pharmacopsychiatry

The current statement is a systematic review of the available data concerning the efficacy of medication treatment of bipolar disorder (BP). A systematic MEDLINE search was made concerning the treatment of BP (RCTs) with the names of treatment options as keywords. The search was updated on 10 March 2012. The literature suggests that lithium, first and second generation antipsychotics and valproate and carbamazepine are efficacious in the treatment of acute mania. Quetiapine and the olanzapine–fluoxetine combination are also efficacious for treating bipolar depression. Antidepressants should only be used in combination with an antimanic agent, because they can induce switching to mania/hypomania/mixed states/rapid cycling when utilized as monotherapy. Lithium, olanzapine, quetiapine and aripiprazole are efficacious during the maintenance phase. Lamotrigine is efficacious in the prevention of depression, and it remains to be clarified whether it is also efficacious for mania. There is some evidence on the efficacy of psychosocial interventions as an adjunctive treatment to medication. Electroconvulsive therapy is an option for refractory patients. In acute manic patients who are partial responders to lithium/valproate/carbamazepine, adding an antipsychotic is a reasonable choice. The combination with best data in acute bipolar depression is lithium plus lamotrigine. Patients stabilized on combination treatment might do worse if shifted to monotherapy during maintenance, and patients could benefit with add-on treatment with olanzapine, valproate, an antidepressant, or lamotrigine, depending on the index acute phase. A variety of treatment options for BP are available today, but still unmet needs are huge. Combination therapy may improve the treatment outcome but it also carries more side-effect burden. Further research is necessary as well as the development of better guidelines and algorithms for the step-by-step rational treatment.

Lithium for prevention of mood episodes in bipolar disorders: systematic review and meta-analysis

BackgroundIn a previous meta-analysis of randomized controlled trials comparing lithium with placebo as a long-term treatment in bipolar disorders, we observed a clear preventative effect for manic episodes; however, the effect was equivocal for depressive episodes. Since then, the evidence base has grown further. In this update, we furthermore present the data on efficacy of lithium in comparison to alternative drug treatments. In addition, we analyze the data comparing lithium with placebo and other treatments regarding drop-outs due to reasons other than a mood episode and completion of study (no mood episode and no drop-out to reasons other than a mood episode).MethodsRandomized controlled trials (RCTs) were sought comparing lithium with placebo and lithium with an alternative treatment in bipolar disorders where the stated intent of treatment was prevention of mood episodes. To this purpose, the Cochrane Central Register of Controlled Trials (CENTRAL) was searched. Reference lists of relevant papers and major textbooks of mood disorders were examined. Authors, other experts in the field, and pharmaceutical companies were contacted for knowledge of suitable trials, published or unpublished.ResultsFor the comparison of lithium with placebo, seven trials (1,580 participants) were included. Lithium was more effective than placebo in preventing overall mood episodes (random effects RR 0.66, 95% CI 0.53 to 0.82), manic episodes (random effects RR 0.52, 95% CI 0.38 to 0.71), and, dependent on the type of analyses applied, depressive episodes (random effects RR 0.78, 95% CI 0.59 to 1.03; fixed effect RR 0.73, 95% CI 0.60 to 0.88). Lithium was inferior to placebo in leading to drop-outs for reasons other than a mood episode (random effects RR 1.33, 95% CI 1.07 to 1.65) but superior to placebo on study completion (random effects RR 1.69, 95% CI 1.12 to 2.55).For the comparison of lithium with anticonvulsants, seven trials were included (n = 1,305). In prevention of manic episodes, lithium showed superiority compared to anticonvulsants (random effects RR 0.66, 95% CI 0.44 to 1.00). However, there was no significant difference regarding prevention of overall mood episodes, depressive episodes, dropping-out to reasons other than a mood episode, or study completion.ConclusionsThe evidence base for lithium in the long-term treatment of bipolar disorders has strengthened. With no other drug available having such ample and consistent evidence for its efficacy lithium remains the most valuable treatment option in this indication.

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders. Part 2: Maintenance Treatment of Major Depressive Disorder-Update 2015

Abstract These guidelines for the treatment of unipolar depressive disorders systematically review available evidence pertaining to the biological treatment of patients with major depression and produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians assessing and treating patients with these conditions. The relevant data have been extracted primarily from various treatment guidelines and panels for depressive disorders, as well as from meta-analyses/reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into five levels of evidence (CE A-F) and five levels of recommendation grades (RG 1–5). This second part of the WFSBP guidelines on depressive disorders covers the management of the maintenance phase treatment, and is primarily concerned with the biological treatment (including pharmacological and hormonal medications, electroconvulsive therapy and other brain stimulation treatments) of adults and also, albeit to a lesser extent, children, adolescents and older adults.

The suicide prevention effect of lithium: more than 20 years of evidence—a narrative review

The management and treatment of patients with suicidal behavior is one of the most challenging tasks for health-care professionals. Patients with affective disorders are at high risk for suicidal behavior, therefore, should be a target for prevention. Numerous international studies of lithium use have documented anti-suicidal effects since the 1970s. Despite the unambiguous evidence of lithium’s anti-suicidal effects and recommendations in national and international guidelines for its use in acute and maintenance therapy of affective disorders, the use of lithium is still underrepresented. The following article provides a comprehensive review of studies investigating the anti-suicidal effect of lithium in patients with affective disorders.

Relationship between sunlight and the age of onset of bipolar disorder: an international multisite study.

BACKGROUND The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. METHODS Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. RESULTS There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. LIMITATIONS Recall bias for onset and family history data. CONCLUSIONS A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.

State of the Art: Treatment of Bipolar Disorders

Bipolar disorders are lifelong lasting affective disorders, with an episodic course of the illness in most cases. The lifetime prevalence is around 2–5%, the illness usually appears in early adulthood and causes significant impairment in psychosocial functioning. This is a selective review focusing on recent developments and issues of interest in the psychopharmacological treatment of bipolar disorders. It is based primarily on the results of adequately powered, randomised, controlled trials (RCTs). These studies were systematically retrieved by means of a Medline search. The past 10 years have led to a broadening of the psychopharmacological treatment options for bipolar disorders. The proof of efficacy for the combination of fluoxetine/olanzapine as well as quetiapine in the acute treatment of bipolar I depression were important steps. While lithium remains the gold standard in the maintenance treatment of bipolar disorders, valproate, olanzapine, lamotrigine, aripiprazole, and quetiapine have been shown efficacious for this indication, with quetiapine possessing the broadest approval status of all drugs for the different treatment phases of this illness. Despite this progress there remains a huge demand regarding new compounds for nearly every area in the psychopharmacological treatment of bipolar disorders. In addition new methodological approaches regarding the proof of effectiveness in clinical practice are urgently needed.

Effect of aripiprazole on cognition in the treatment of patients with schizophrenia.

BACKGROUND The aim of this study was to assess the cognitive effects of aripiprazole in inpatients with schizophrenia. METHODS This was an investigator-initiated, open label eight-week trial evaluating 56 inpatients with the DSM-IV diagnosis of schizophrenia. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and tolerability was assessed each week using the Udvalg for Klinske Undersogelser side effect rating scale (UKU). Cognitive function was assessed at baseline, week 4 and week 8. RESULTS Aripiprazole showed significant improvement in PANSS total score and all subscores between baseline and endpoint visit. The substance was very well tolerated. Patients improved significantly in verbal memory, reaction time and reaction quality/attention from baseline to week eight. Furthermore, mean z-values of individual cognitive domains summarized in a global cognitive index improved significantly from baseline to week eight. DISCUSSION Our results suggest that aripiprazole provides a valuable treatment option for patients with schizophrenia.

DSM-5 reviewed from different angles: goal attainment, rationality, use of evidence, consequences—part 2: bipolar disorders, schizophrenia spectrum disorders, anxiety disorders, obsessive–compulsive disorders, trauma- and stressor-related disorders, personality disorders, substance-related and addictive disorders, neurocognitive disorders

Abstract Part 1 of this paper discussed several more general aspects of Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and offered a detailed, paradigmatic analysis of changes made to the chapter on depressive disorders. This second part focusses on several other disorders, including bipolar and schizophrenia spectrum disorders. The respective changes and their possible consequences are discussed under consideration of traditional psychiatric classification, particularly from the perspective of European traditions and on the basis of a PubMed search and review papers. The general conclusion is that even seemingly small changes such as the introduction of the mixed feature specifier can have far-reaching consequences. Contrary to the original plans, DSM-5 has not radically changed to become a primarily dimensional diagnostic system but has preserved the categorical system for most disorders. The ambivalence of the respective decision-making becomes apparent from the last minute decision to change the classification of personality disorders from dimensional back to categorical. The advantages and disadvantages of the different approaches are discussed in this context. In DSM-5, only the chapter on addictive disorders has a somewhat dimensional structure. Also in contrast to the original intentions, DSM-5 has not used a more neurobiological approach to disorders by including biological markers to increase the objectivity of psychiatric diagnoses. Even in the most advanced field in terms of biomarkers, the neurocognitive disorders, the primarily symptom-based, descriptive approach has been preserved and the well-known amyloid-related and other biomarkers are not included. This is because, even after so many years of biomarker research, the results are still not considered to be robust enough to use in clinical practice.

Diagnosing bipolar disorders in DSM-5

Editorial A few weeks ago, after many years of intensive work, the much-awaited fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) was published. It is still the case today that psychiatric diagnoses seem to be more consensus-based than validity-based (Cuthbert and Insel 2013; Bschor et al. 2012; Berk 2013) something that DSM-5 will also be unable to change. In spite of this, DSM-5 introduces several important changes with regard to diagnostic criteria for bipolar disorders. The International Journal of Bipolar Disorders is honored that Jules Angst, whose work has made an outstanding contribution to the modifications regarding bipolar disorders in DSM-5 (Angst et al. 2011, 2012), has agreed to comment on the strengths, problems and perspectives relating to these changes in the paper that accompanies this editorial (Angst 2013). An essential topic thankfully addressed by Jules Angst in the accompanying paper (Angst 2013) has been hotly debated within the psychiatric scientific community throughout the last few years namely whether bipolar disorders are much more frequent than previously assumed. If this is the case, one may conclude that the hitherto existing diagnostic criteria have falsely prevented the proper diagnosis of all cases of bipolar disorders on account of their being overly restrictive. In DSM-5, bipolar and related disorders, as they are now called, are given a chapter on their own, between depressive disorders and schizophrenia spectrum disorders, that includes bipolar I disorder (which represents, according to DSM-5, classic manic depressive disorder, with the exception that neither a depressive episode nor psychosis has to be present for diagnosis), bipolar II disorder and cyclothymic disorder. Furthermore, in this chapter, there are now separate diagnostic criteria for