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Background: Bipolar disorder (short: BD) is a severe illness with very heterogeneous trajectories. While some of the patients show no or hardly any long-term impairments, other affected individuals show substantial neurocognitive deficits with a clear decline in psychosocial functioning. Which factors influence the course of the disease is the subject of current research efforts.

Objective: This review presents the long-term course of bipolar disease and the factors influencing it. In particular, differential trajectory types are discussed. The cognitive and psychosocial functional level as well as the psychopathological characteristics of the disease are elucidated. In addition, biological factors and treatment approaches influencing the course and prognosis are identified.

Material and methods: Literature search using PubMed focusing on longitudinal studies over several years (see online supplement).

Results: To date, there are only a few predictors and biomarkers that allow prediction of long-term progression. None have been sufficiently studied to enable clinical use. Appropriate pharmacological and psychotherapeutic treatment of those affected is essential to avoid renewed episodes of the disease.

Discussion: The long-term course of bipolar disorder is highly heterogeneous and multifaceted. Despite intensive research efforts, no predictors have yet been identified that reliably predict the clinical course. This makes further research all the more important in order to offer individualized therapy options, develop new therapies and positively influence the course of the disease at an early stage.

Background: Self-help can play an important supplementary role in the treatment of people with severe mental illness; however, little is known about the utilization of the various approaches.

Objective: This study describes the use of various self-help options by patients with severe mental illness and examines potential predictors.

Material and methods: As part of the observational cross-sectional study on patients with severe mental illness (IMPPETUS, N = 397), trained staff collected sociodemographic, illness-associated and treatment-associated data between March 2019 and September 2019. Binary logistic regression was used to analyze a possible association with the use of self-help.

Results: The participants most frequently reported using self-help literature (n = 170; 45.5%) followed by self-help groups (n = 130; 33.2%), electronic mental health applications (n = 56; 15.5%) and self-management approaches (n = 54; 14.8%). Trialogue seminars (n = 36; 9.9%) were the least used by the participants. The utilization of the various approaches is influenced by sociodemographic and disease-related characteristics (age, education, marital status, migration background, age at onset of initial mental health problems, psychosocial functioning level) but not by factors associated with treatment.

Conclusion: The potential of self-help is not being fully utilized in the sample investigated. The reported use of self-help approaches by the participants ranged between 10% and 46%. The various formats address specific target groups. More targeted information must be provided about the various options and the use of self-help in routine treatment must be actively fostered in order to increase the utilization of self-help.

Cognitive disorders are multifaceted and the range of neuropsychological instruments is correspondingly extensive; however, most examiners have to limit themselves to a small selection in order to master them safely. In geriatric patients the various forms and stages of dementia dominate. Delirium must be distinguished from these as an acute life-threatening event. The personal and external medical history as well as clinical observation are the first steps in the assessment of cognition; the selection of test procedures is graduated and bears the patient's benefit in mind. When compiling a toolbox for use in one's own field of work, in addition to instruments focusing on different degrees of severity, alternatives should also be considered for use in the presence of comorbidities that reduce the validity (visual, hearing and fine motor disorders) and the examination situation should be taken into account.

Background: At present there is no comprehensive overview of the long-term development of the clinical picture, disease-associated impairments and neurobiological correlates of anxiety disorders as well as what influence certain risk factors and treatment have on the prognosis.

Objective: This article presents findings regarding disorder-specific symptoms and disorder-associated changes in the areas of functional level, quality of life, neurocognitive performance and structural brain anatomy over the lifespan. It also reports on how patient-related and environment-related aspects as well as guideline-oriented therapy influence the course of the disorder.

Material and methods: A literature search was conducted in PubMed on the aspects of individual components. Meta-analyses, longitudinal and cohort studies were included. To illustrate changes over time, the findings were predominantly presented separately for children and adolescents as well as for early and late adulthood.

Results: Anxiety disorders primarily exhibit age-associated differences in the symptom profile but also in the areas of functional level and quality of life. Risk factors for an unfavorable course of the disorder were identified particularly for young and middle-aged people; however, the findings indicate that evidence-based psychotherapy or pharmacotherapy also has a lasting effect even after termination.

Conclusion: For long-term therapeutic success, age-dependent characteristics and limitations as well as prognostically relevant aspects in the diagnostics and treatment of anxiety disorders should be taken into consideration and treatment should be started as soon as possible.

Background: Blinded placebo treatment arms in clinical trials often achieve up to 80% of the clinical improvements of the verum groups. Apparently, the majority of the effects found in the antidepressant groups in clinical trials are due to factors that are not specific to antidepressant treatment. This article reviews the factors that contribute to the high effectiveness of placebo interventions for antidepressants.

Methods: A narrative literature review is presented with particular emphasis on placebo effects in antidepressant clinical trials.

Results: There is a particularly strong placebo effect in depression compared to other mental disorders. The magnitude of this effect can be modulated by helpful versus nonhelpful instructions, by patient participation in the decision-making process but also by personal attention, especially if the clinician is perceived as competent and warmhearted. The occurrence of subtle side effects can also reinforce placebo effects. Placebo effects are not only reflected in subjective patient-reported outcome variables but are also evident in neurochemical changes in the body.

Conclusion: Clinicians essentially contribute to the effectiveness of antidepressant treatment through their own behavior. At the same time, the relatively small overall difference between verum and placebo treatments for depression leads to the necessity of a critical evaluation of the cost-benefit ratio, adapted to the individual case. Study designs for the evaluation of antidepressants are required that better reflect the complex interactions between the genuine drug effects and placebo effects.

Background: Antidepressant pharmacotherapy often does not result in the desired effect despite adequate duration and dose. Better evidence on second-step strategies is needed.

Objective: Overview of the current evidence for various pharmacological second-step strategies after nonresponse to antidepressant monotherapy.

Material and methods: Summary of recent systematic reviews with meta-analyses of the group of authors on pharmacological second-step treatment.

Results: A meta-analysis showed no advantage of switching to a second antidepressant compared with continuing the previously ineffective monotherapy. Another two meta-analyses showed no benefit of increasing the dose of selective serotonin reuptake inhibitors (SSRI). For serotonin and noradrenaline reuptake inhibitors (SNRI) and tricyclic antidepressants (TCA) in each case a meta-analysis showed no clear advantage of increasing the dose. Another two meta-analyses showed a superiority of a combination therapy consisting of a reuptake inhibitor (SSRI, SNRI, TCA) with a presynaptic alpha‑2 autoreceptor antagonist (e.g., mirtazapine) compared with an antidepressant monotherapy.

Conclusion: In accordance with the recommendations of the German national treatment guideline, in the event of nonresponse to antidepressant monotherapy, the combination of two antidepressants is preferable to repeated switching of the antidepressant.