Antidepressant-Resistant Depression and Antidepressant-Associated Suicidal Behaviour: The Role of Underlying Bipolarity

The complex relationship between the use of antidepressants and suicidal behaviour is one of the hottest topics of our contemporary psychiatry. Based on the literature, this paper summarizes the author's view on antidepressant-resistant depression and antidepressant-associated suicidal behaviour. Antidepressant-resistance, antidepressant-induced worsening of depression, antidepressant-associated (hypo)manic switches, mixed depressive episode, and antidepressant-associated suicidality among depressed patients are relatively most frequent in bipolar/bipolar spectrum depression and in children and adolescents. As early age at onset of major depressive episode and mixed depression are powerful clinical markers of bipolarity and the manic component of bipolar disorder (and possible its biological background) shows a declining tendency with age antidepressant-resistance/worsening, antidepressant-induced (hypo)manic switches and “suicide-inducing” potential of antidepressants seem to be related to the underlying bipolarity

How to save a life. From neurobiological underpinnings to psychopharmacotherapies in the prevention of suicide

The impact of suicide on our societies, mental healthcare, and public health is beyond questionable. Every year approximately 700 000 lives are lost due to suicide around the world (WHO, 2021); more people die by suicide than by homicide and war. Although suicide is a key issue and reducing suicide mortality is a global imperative, suicide is a highly complex biopsychosocial phenomenon, and in spite of several suicidal models developed in recent years and a high number of suicide risk factors identified, we still have neither a sufficient understanding of underpinnings of suicide nor adequate management strategies to reduce its prevalence. The present paper first overviews the background of suicidal behavior including its epidemiology, age and gender correlations, and its association with neuropsychiatric disorders as well as its clinical assessment. Then we give an overview of the etiological background, including its biopsychosocial contexts, genetics and neurobiology. Based on the above, we then provide a critical overview of the currently available intervention options to manage and reduce risk of suicide, including psychotherapeutic modalities, traditional medication classes also providing an up-to-date overview on the antisuicidal effects of lithium, as well as novel molecules such as esketamine and emerging medications and further molecules in development. Finally we give a critical overview on our current knowledge on using neuromodulatory and biological therapies, such as ECT, rTMS, tDCS, and other options.(c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)

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

How can the depressed mind extract and remember predictive relationships of the environment? evidence from implicit probabilistic sequence learning

A growing body of evidence suggests that emotion and cognition are fundamentally intertwined; impairments in explicit, more effortful and attention-dependent cognitive functions have widely been observed in negative mood. Here we aimed to test how negative mood affects implicit cognition that is less susceptible to motivational and attentional factors associated with negative mood. Therefore, we examined implicit learning and retention of predictive relationships in patients with major depressive episode (MDE). Additionally, we directly compared subgroups of patients with major depressive disorder (MDD) vs. bipolar disorder (BD) in order to gain a deeper understanding of how implicit cognition is affected by these conditions. Implicit probabilistic sequence learning was measured by the Alternating Serial Reaction Time Task. The acquired knowledge was retested after a 24-hour delay period. Consistent with the frontostriatal deficits frequently reported in depression, we found weaker learning in patients with MDE, with a more pronounced deficit in patients with MDD compared to BD. After the 24-hour delay, MDE patients (both subgroups) showed forgetting, while the controls retained the previously acquired knowledge. These results cannot be explained by alterations in motivation, attention and reward processing but suggest more profound impairments of implicit learning and retention of predictive relationships among neutral stimuli in depression. To the best of our knowledge, this is the first study investigating retention of implicitly acquired sequential knowledge and reporting deficits in this domain in MDE. Our findings not only contribute to a better understanding of the complex interplay between affect and cognition but can also help improve screening, diagnosis and treatment protocols of depression

A real-world, prospective, multicenter, single-arm observational study of duloxetine in patients with major depressive disorder or generalized anxiety disorder

Background: Suboptimal treatment response during anti-depressive treatment is fairly common with the first antidepressant (AD) choice, followed by switching to another agent in the majority of cases. However, the efficacy of this strategy over continuation of the original agent is less solidly documented in real-life studies. The aim of our present study was to ascertain the effects of switching to duloxetine following inadequate response to prior ADs on general illness severity, pain, and health-related quality of life in a large sample of major depressive disorder (MDD) and generalized anxiety disorder (GAD) patients in a prospective, real-world, multicenter, observational study. Methods: A total of 578 participants with MDD or GAD were enrolled in 58 outpatient sites in an 8-week, single-arm, open-label, flexible-dose trial with duloxetine. Severity of symptoms [with Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I)], severity of pain (with a Visual Analog Scale), satisfaction with current treatment, and health-related quality of life [with the three-level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L)] measures were recorded at baseline and at follow-up visits 4 and 8 weeks after initiation of treatment. Data were analyzed using ANOVA and mixed linear models. Results: 565 patients completed the study and comprised the analyzed dataset. Results indicated that severity of illness significantly decreased over the 8 weeks of the study and already at 4 weeks in both patient groups. Overall quality of life and all of its subindicators also significantly improved in both patient groups and so did subjective experience of pain. Satisfaction with current treatment also significantly increased during the study period. Frequency of side effects was low. In both GAD and MDD groups, two patients dropped out of the study due to adverse effects, leading to treatment termination in four cases (0.7%). Conclusions: This 8-week, multicenter, flexible-dosing, single-arm, open-label, observational real-life study in MDD and GAD patients switched to duloxetine after inadequate response or low tolerability to other ADs showed a significant positive effect on all outcome measures, including a significant decrease in illness severity as well as significant overall symptomatic improvement, with good tolerability

Alexithymia and Suicide Risk in Psychiatric Disorders: A Mini-Review.

It is well known that alexithymic individuals may show significantly higher levels of anxiety, depression, and psychological suffering than non-alexithymics. There is an increasing evidence that alexithymia may be considered a risk factor for suicide, even simply increasing the risk of development of depressive symptoms or per se. Therefore, the purpose of this narrative mini-review was to elucidate a possible relationship between alexithymia and suicide risk. The majority of reviewed studies pointed out a relationship between alexithymia and an increased suicide risk. In several studies, this relationship was mediated by depressive symptoms. In conclusion, the importance of alexithymia screening in everyday clinical practice and the evaluation of clinical correlates of alexithymic traits should be integral parts of all disease management programs and, especially, of suicide prevention plans and interventions. However, limitations of studies are discussed and must be considered

MOOD SYMPTOMS IN STABILIZED PATIENTS WITH SCHIZOPHRENIA: A BIPOLAR TYPE WITH PREDOMINANT PSYCHOTIC FEATURES?

Background: Schizophrenia (SZ) and bipolar disorder (BD) are traditionally distinguished on the basis of progressive deterioration and long-term outcome, but a more dimensional approach is warranted. There are limited data on the occurrence of manic symptoms in patients with schizophrenia. The aim of the current study was to search for patterns in the clinical symptomatology, which may suggest the presence of one or several mood disorders under the label of schizophrenia. Subjects and methods: Hundred-seventy-five patients diagnosed with schizophrenia according to DSM-5 were included in the study. The psychometric assessment included the Positive and Negative Syndrome Scale, Young Mania Rating Scale, The Montgomery- Åsberg Depression Rating Scale and the Calgary Depression Scale. The statistical analysis included MANOVA, Pearson Correlation coefficient and principal components analysis. Results: Significant subthreshold manic symptoms were present in 25.14% of patients. Mood symptoms correlated with positive symptoms. The PCA revealed a complex structure with 15 factors (one positive, negative, somatic, anxiety, neurocognitive, disorganization and manic, five depressive and three psychomotor/excitement/hostility/violence). Conclusion: Psychotic mood disorders are often phenotypically indistinguishable from schizophrenia, so it is likely that psychotic affective patients have been misdiagnosed with schizophrenia. The current study suggests that there seem to be patients with mania misdiagnosed as \u27schizophrenics\u27 because of the presence of psychotic features, a condition better described as \u27schizophreniform bipolar disorder\u27