Mixed Depression: A Mini-Review to Guide Clinical Practice and Future Research Developments.

The debate on mixed states (MS) has been intense for decades. However, several points remain controversial from a nosographic, diagnostic, and therapeutic point of view. The different perspectives that have emerged over the years have turned into a large, but heterogeneous, literature body. The present review aims to summarize the evidence on MS, with a particular focus on mixed depression (MxD), in order to provide a guide for clinicians and encourage the development of future research on the topic. First, we review the history of MS, focusing on their different interpretations and categorizations over the centuries. In this section, we also report alternative models to traditional nosography. Second, we describe the main clinical features of MxD and list the most reliable assessment tools. Finally, we summarize the recommendations provided by the main international guidelines for the treatment of MxD. Our review highlights that the different conceptualizations of MS and MxD, the variability of clinical pictures, and the heterogeneous response to pharmacological treatment make MxD a real challenge for clinicians. Further studies are needed to better characterize the phenotypes of patients with MxD to help clinicians in the management of this delicate condition.

Athanasios Koukopoulos' Psychiatry: The Primacy of Mania and the Limits of Antidepressants.

BACKGROUND: Athanasios Koukopoulos provided a radical model for understanding depressive and manic conditions. OBJECTIVE: To review, explain, and analyze Koukopoulos' concept of the primacy of mania, with special attention to the role of antidepressants. METHOD: A conceptual review of Koukopoulos' writings and lectures on this topic is given. RESULTS: Koukopoulos held that depressive states are caused by manic states; the former do not occur without the latter. The most common scenario of the inseparability of depressive and manic symptoms occurs in mixed states, which we estimate to represent about one-half of all depressive episodes in all patients (not just bipolar illness). In a review of the empirical evidence for this topic, we conclude that empirical evidence exists to support the primary of mania thesis in almost 80% of depressed patients. Since antidepressants worsen mania, they would be expected to worsen depression as well in this model. We provide evidence that supports this view in most persons with depressive states. CONCLUSION: Koukopoulos' model of affective illness is one where manic states are the primary pathology, and depressive conditions are a secondary consequence. Hence treatment of depression with antidepressants would be less effective than treatment with mood stabilizers, since treating an effect is less successful than treating its cause. This approach would reverse current assumptions in psychiatry.

The bipolar spectrum: conceptions and misconceptions.

OBJECTIVE: This review aims to address concerns about the potential overinclusiveness and vagueness of bipolar spectrum concepts, and also, concerns about the overlap between bipolar illness and borderline personality. METHOD: Narrative review based on historical and empirical studies. RESULTS: Bipolar disorder (BD) and major depressive disorder (MDD) came to be separate entities with the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM III), in contrast to the Kraepelinian manic-depressive insanity (MDI) concept, which included both. The bipolar spectrum concept is a return to this earlier Kraepelinian perspective. Further, very different features differentiate the disease of bipolar illness (family history of bipolar illness, severe recurrent mood episodes with psychomotor activation) from the clinical picture of borderline personality (dissociative symptoms, sexual trauma, parasuicidal self-harm). The term 'disorder' obfuscates an ontological difference between diseases, such as manic-depressive illness, and clinical pictures, such as hysteria/post-traumatic stress disorder/dissociation/borderline personality. CONCLUSIONS: Bipolar spectrum concepts are historically rooted in Kraepelin's manic-depressive illness concept, are scientifically testable, and can be clearly formulated. Further, they differ in kind from traumatic/dissociative conditions in ways that can be both historically and scientifically established.

Bipolar spectrum: a review of the concept and a vision for the future.

This paper reviews the bipolar spectrum concept historically and empirically. It describes how the concept derives from Kraepelin, but was lost with DSM-III, which divided the broad manic-depressive illness concept, based on recurrent mood episodes of either polarity, to the bipolar versus unipolar dichotomy, based on allowing non-recurrent mood episodes of only one polarity. This approach followed the views of Karl Leonhard and other critics of Kraepelin. Thus post DSM-III American psychiatry is not neo-Kraepelinian, as many claim, but neo-Leonhardian. The bipolar spectrum approach, as advocated by Akiskal and Koukopoulos first, harkens back to the original broad Kraepelinian view of manic-depressive illness. The evidence for and against this approach is discussed, and common misconceptions, including mistaken claims that borderline personality is similar, are revealed and critiqued.

Bipolar Spectrum: A Review of the Concept and a Vision for the Future

This paper reviews the bipolar spectrum concept historically and empirically. It describes how the concept derives from Kraepelin, but was lost with DSM-III, which divided the broad manic-depressive illness concept, based on recurrent mood episodes of either polarity, to the bipolar versus unipolar dichotomy, based on allowing non-recurrent mood episodes of only one polarity. This approach followed the views of Karl Leonhard and other critics of Kraepelin. Thus post DSM-III American psychiatry is not neo-Kraepelinian, as many claim, but neo-Leonhardian. The bipolar spectrum approach, as advocated by Akiskal and Koukopoulos first, harkens back to the original broad Kraepelinian view of manic-depressive illness. The evidence for and against this approach is discussed, and common misconceptions, including mistaken claims that borderline personality is similar, are revealed and critiqued.