[Bipolar depression, a challenge diagnostic and treatmentwise].

This narrative review addresses the challenges of how to identify and treat bipolar depression. Bipolar depression, i.e. depressive episode(s) as part of bipolar disorder, can be differentiated from unipolar depression only through the previous course of illness. A correct diagnosis therefore may be delayed. The pharmacotherapy of bipolar depression differs from that of unipolar depression due to a high risk of recurrence of either hypomanic/manic or depressive episodes or mood instability. Therefore, long periods of specialized treatment will often be required. Both bipolar and unipolar depression will often benefit from adjunctive social and psychological interventions.

The Relationship between Affect Integration and Psychopathology in Patients with Personality Disorder: A Cross-Sectional Study.

Background and Objectives: Emotional dysfunction is considered a key component in personality disorders; however, only few studies have examined the relationship between the two. In this study, emotional dysfunction was operationalized through the Affect Integration Inventory, and the aim was to examine the relationships between the level of affect integration and the levels of symptom distress, interpersonal problems, and personality functioning in patients diagnosed with personality disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Materials and Methods: Within a hospital-based psychiatric outpatient setting, 87 patients with personality disorder referred for treatment were identified for assessment with the Affect Integration Inventory and other measures (e.g., the Symptom Checklist-90, Revised, the Inventory of Interpersonal Problems 64 circumplex version, and the Severity Indices of Personality Problems). Results: The analyses revealed that problems with affect integration were strongly and statistically significantly correlated with high levels of symptom distress, interpersonal problems, and maladaptive personality functioning. Additionally, low scores on the Affect Integration Inventory regarding discrete affects were associated with distinct and differentiated patterns of interpersonal problems. Conclusion: Taken together, emotional dysfunction, as measured by the Affect Integration Inventory, appeared to be a central component of the pathological self-organization associated with personality disorder. These findings have several implications for the understanding and psychotherapeutic treatment of personality pathology. Furthermore, they highlight the importance of considering the integration of discrete affects and their specific contributions in the conceptualization and treatment of emotional dysfunction in patients with personality disorders.

The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study.

OBJECTIVE: To investigate the efficacy of adjunctive N-acetylcysteine (NAC) for the treatment of acute bipolar depression. METHOD: A randomized, double-blind, multicentre, placebo-controlled trial including adult subjects diagnosed with bipolar disorder, currently experiencing a depressive episode. Participants were treated with 3 g/day NAC or placebo as an adjunctive to standard treatment for 20 weeks, followed by a 4-week washout where the blinding was maintained. The primary outcome was the mean change in the Montgomery Asberg Depression Rating Scale (MADRS) score over the 20-week treatment phase. Linear Mixed Effects Repeated Measures (LMERM) was used for analysing the primary outcome. RESULTS: A total of 80 subjects were included. The mean MADRS score at baseline was 30.1 and 28.8 in participants randomized to NAC and placebo, respectively. Regarding the primary outcome measure, the between-group difference (NAC vs. placebo) was 0.5, which was statistically non-significant (95% CI: -7.0-5.9;p = 0.88). All findings regarding secondary outcomes were statistically or clinically insignificant. LIMITATIONS: The study had a placebo response rate of 55.6% - high placebo response rates are associated with failure to separate from placebo. CONCLUSIONS: Based on our primary outcome measure, we could not confirm previous studies showing a therapeutic effect of adjunctive NAC treatment on acute bipolar depression. Further studies with larger samples are needed to elucidate if specific subgroups could benefit from adjunctive NAC treatment.

Add-on treatment with N-acetylcysteine for bipolar depression: a 24-week randomized double-blind parallel group placebo-controlled multicentre trial (NACOS-study protocol).

BACKGROUND: Oxidative stress and inflammation may be involved in the development and progression of mood disorders, including bipolar disorder. Currently, there is a scarcity of useful treatment options for bipolar depressive episodes, especially compared with the efficacy of treatment for acute mania. N-Acetylcysteine (NAC) has been explored for psychiatric disorders for some time given its antioxidant and anti-inflammatory properties. The current trial aims at testing the clinical effects of adjunctive NAC treatment (compared to placebo) for bipolar depression. We will also explore the biological effects of NAC in this context. We hypothesize that adjunctive NAC treatment will reduce symptoms of depression, which will be reflected by changes in selected markers of oxidative stress. METHODS AND ANALYSIS: In the study, we will include adults diagnosed with bipolar disorder, in a currently depressive episode. Participants will undertake a 20-week, adjunctive, randomized, double-blinded, parallel group placebo-controlled trial comparing 3 grams of adjunctive NAC daily with placebo. The primary outcome is the mean change over time from baseline to end of study on the Montgomery-Asberg Depression Rating Scale (MADRS). Among the secondary outcomes are mean changes from baseline to end of study on the Bech-Rafaelsen Melancholia Scale (MES), the Young Mania Rating Scale (YMRS), the WHO-Five Well-being Index (WHO-5), the Global Assessment of Functioning scale (GAF-F), the Global Assessment of Symptoms scale (GAF-S) and the Clinical Global Impression-Severity scale (CGI-S). The potential effects on oxidative stress by NAC treatment will be measured through urine and blood samples. DNA will be examined for potential polymorphisms related to oxidative defences. TRIAL REGISTRATION: Registered at The European Clinical Trials Database, ClinicalTrials.gov: NCT02294591 and The Danish Data Protection Agency: 2008-58-0035.

[Treatment of mania in adults].

Around 1% of the population will experience at least one episode of mania. Mania has negative social consequences, may lead to cognitive impairment and may even be lethal. Therefore, prompt and efficient medical action needs to be taken, not only addressing the acute symptoms but also the high risk of recurrence. Many well-documented antimanic drugs are at hand, and the database has been carefully outlined in recent guidelines, also addressing factors of importance in choosing among the options. The real challenge is dealing with non-response, where the database is extremely poor.

Letter to the editor: is it valid to break down results from long-term trials in bipolar disorder by polarity of relapses?

When analysing and reporting data from long-term drug trials in bipolar disorder, it has become the standard to break down the outcome into the prevention of mania and the prevention of depression. However, as illustrated by a theoretical example, this approach may confer a potential analysis bias. The point is that when mania or depression, whatever appears first, is considered an endpoint, then an endpoint of mania will exclude an endpoint of depression and vice versa. The risk of such bias is reduced when the time course is taken into consideration in the analysis.

Affective temperaments' relation to functional impairment and affective recurrences in bipolar disorder patients.

BACKGROUND: The prognostic significance of affective temperaments in bipolar disorder is not yet fully understood. This study therefore examined the relationship between affective temperaments and two major illness outcomes in bipolar disorder: functional impairment and affective recurrences. METHOD: At baseline fifty-one remitted bipolar disorder patients were administered the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego Auto-questionnaire (TEMPS-A), and the Work and Social Adjustment Scale (WSAS). The patients were followed for 24 months as part of their routine treatment. At follow-up, data on affective recurrences were obtained through medical records combined with a semi-structured interview that enquired into medication adherence. RESULTS: Scores on the cyclothymic temperament correlated significantly with functional impairment overall and with scores in three function domains: home-management, private leisure activities and social leisure activities. High scores on the cyclothymic temperament also significantly predicted the presence of depressive recurrences even when controlling for medication non-adherence. The presence of hypomanic or manic recurrences was not predicted by scores on any of the affective temperaments. LIMITATION: Since all of the bipolar patients were newly diagnosed and therefore relatively young, the representativeness of the results may have been reduced. The prospective part of the study used data from medical records that may not be as systematic as data gathered from structured clinical interviews. CONCLUSION: By suggesting that the cyclothymic temperament is related to both functional impairment and depressive recurrences the findings highlight a vulnerability area in need of further exploration in terms of its prognostic significance.

Severity of affective temperament and maladaptive self-schemas differentiate borderline patients, bipolar patients, and controls.

OBJECTIVES: There is an unsettled debate on whether borderline personality disorder and bipolar disorder should be considered related or distinct. This study aimed to further the understanding of the similarities and differences between the 2 disorders by comparing borderline patients, bipolar patients, and controls in terms of various affective temperaments and maladaptive self-schemas. METHODS: The sample consisted of 85 participants (31 borderline patients, 25 bipolar patients and 29 student controls) who completed 2 questionnaires: The Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire and the Young Schema Questionnaire. All of the patients were in remission from affective episodes. RESULTS: Compared to the bipolar patients and the controls, the borderline patients were characterized by significantly higher mean scores on most of the maladaptive self-schemas and affective temperaments. The bipolar patients differed significantly from controls by higher mean scores on the cyclothymic temperament and insufficient self-control. CONCLUSIONS: The study suggests that affective temperaments and maladaptive self-schemas are more severe in borderline patients than in bipolar patients. These findings point to phenomenological differences between the 2 disorders and therefore question their degree of kinship.

[Prophylactic treatment of affective disorders]. / Forebyggende behandling ved affektive lidelser.

Due to the episodic nature of affective disorders, treatments that prevent relapses/recurrences have a high priority. The number of long-term studies is scarce, but for moderate and severe cases of recurrent depression and for most cases of bipolar disorder, there is enough evidence to recommend various psychological interventions in combination with long-term pharmacotherapy (mainly antidepressants for recurrent depression and mainly lithium for bipolar disorder). Even though none of the treatments cause dramatic risk reduction, it is often possible to improve the individual prognosis through integrated long-term management by specialized teams.

[Preventive drug therapy of depressions]. / Forebyggende, medikamentel behandling af depressionssygdommen.

At least 5-10 per cent of the Danish population will during their lifetime experience more than one episode of major depression but only a minority of this group will receive the necessary and sufficient prophylactic treatment against their illness. Randomised controlled studies have shown that the majority of commonly used antidepressant drugs, new as well as old ones, possess prophylactic efficacy. Thus, treatment efficacy is not a major problem but the treatment efficiency in everyday clinical practice is unsatisfactory. This is partly due to a lack of relevant treatment facilities for psychiatric patients, partly to a lack of knowledge among patients and their relatives but also among doctors of the indications for prophylactic treatment against recurrent depression and the technical issues involved. A short practical guideline for prophylactic treatment against recurrent depression will appear from the article.