The use of antiepileptic drugs in bipolar disorders: a review based on evidence from controlled trials

Antiepileptic drugs (AEDs) have diverse psychotropic profiles. Some AEDs have proven to be efficacious in the treatment of mood disorders, especially bipolar disorder. Others are ineffective as primary treatments but may be useful adjuncts for mood disorders or comorbid conditions. Valproate (acute mania and mixed episodes), carbamazepine (acute mania and mixed episodes), and lamotrigine (maintenance to delay recurrence) have United States Food and Drug Administration indications for the treatment of bipolar disorder. This article provides an overview of data on the use of AEDs in bipolar disorder, including acute mania and depression, prophylaxis, and rapid cycling.     

Brain imaging in catatonia: current findings and a pathophysiologic model

Karl Ludwig Kahlbaum originally described catatonia as a psychomotor disease that encompassed motor, affective, and behavioral symptoms. In the beginning of the 20th century, catatonia was considered to be the motoric manifestation of schizophrenia; therefore, neuropathologic research mostly focused on neuroanatomic substrates (ie, the basal ganglia underlying the generation of movements). Even though some alterations were found in basal ganglia, the findings in these subcortical structures are not consistent. Recently, there has been a reemergence of interest into researching catatonia. Brain imaging studies have shown major and specific alterations in a right hemispheric neural network that includes the medial and lateral orbitofrontal and posterior parietal cortex. This neural network may be abnormally modulated by altered functional interactions between gamma-aminobutyric acid (GABA)-ergic and glutamatergic transmission. This may account for the interrelationship among motor, emotional, and behavioral alterations observed in both clinical phenomenology and the subjective experiences of patients with catatonia. Such functional interrelationships should be explored in further detail in catatonia, which may also serve as a paradigmatic model for the investigation of psychomotor and brain function in general.     

The universal field hypothesis of catatonia and neuroleptic malignant syndrome

Catatonia and neuroleptic malignant syndrome (NMS) are uncommon disorders that can be life-threatening. Many researchers consider them as clinically divergent entities; however, they share similar and overlapping literature on causative agents, phenomenology, and treatment response. This hypothesis considers both disorders as a single entity that result from variable combinations of the following: 1) gamma-aminobutyric acid (GABA) hypoactivity at the GABAA receptor; 2) dopamine hypoactivity at the D2 receptor; 3) serotonin hyperactivity at the 5-HT1A receptor and hypoactivity at the 5-HT2A receptor; and 4) glutamate hypoactivity at the N-methyl-D-aspartate (NDMA) receptor. In this paper, evidence to support this hypothesis is limited to retrospective human studies of catatonia and NMS. The four components of the hypothesis are: 1) GABAA agonists have been shown to alleviate catatonia and NMS; 2) D2 antagonism is proportional to the relative likelihood of NMS and catatonia; 3) 5-HT1A agonism with 5-HT2A antagonism is implicated in catatonia and NMS; 4) NMDA receptor antagonists, such as phencyclidine and ketamine, reduce glutamate transmission. This hypothesis proposes that it is the interaction of these systems that prediposes, initiates, and maintains the twin syndromes of catatonia and NMS.     

Dyskinesias differentiate autistic disorder from catatonia

Autistic disorder and catatonia are neuropsychiatric syndromes defined by impairments in social interaction, communication, and restricted, stereotypical motor routines. Assessments of children with these disorders are typically restricted in scope by the patients' limited ability to comprehend directions. The authors performed systematic assessments of dyskinesias on six prepubertal boys with autistic disorder and mental retardation and on one adolescent male with catatonia to determine if this type of information could be routinely obtained. The boys with autistic disorder had more stereotypies and tics, a greater degree of akathisia and hyperactivity, and more compulsions than the adolescent with catatonia. Catatonia was associated with catalepsy and dystonic postures. The authors conclude that the diagnostic accuracy and specificity of neuropsychiatric syndromes may be enhanced by the systematic assessment of the dyskinesias associated with each condition.     

"Scared stiff": catatonia as an evolutionary-based fear response

Catatonia, long viewed as a motor disorder, may be better understood as a fear response, akin to the animal defense strategy tonic immobility (after G. G. Gallup & J. D. Maser, 1977). This proposal, consistent with K. L. Kahlbaum's (1874/1973) original conception, is based on similarities between catatonia and tonic immobility ("death feint") as well as evidence that catatonia is associated with anxiety and agitated depression and responds dramatically to benzodiazepines. It is argued that catatonia originally derived from ancestral encounters with carnivores whose predatory instincts were triggered by movement but is now inappropriately expressed in very different modern threat situations. Found in a wide range of psychiatric and serious medical conditions, catatonia may represent a common "end state" response to feelings of imminent doom and can serve as a template to understand other psychiatric disorders.     

Athanasios Koukopoulos (1931–2013)

With the death of Athanasios Koukopoulos last year, psychiatry lost one of its most stimulating and scientifically influential representatives has been lost. His main scientific contributions are in the course of manic depressive illnesses and mixed affective states. Perhaps his most important contribution to modern psychiatry are his studies on the use of antidepressants in bipolar disorder. He was able to show that antidepressants attenuate the beneficial effects of lithium, can trigger mania, and can lead to cycle acceleration and rapid cycling.     

An analysis of 17 catatonic patients diagnosed with neuroleptic malignant syndrome

This study was conducted to show that catatonia is a predisposing factor for neuroleptic malignant syndrome (NMS) and to review the nosological relationship between catatonia and NMS. Seventeen consecutive cases of NMS were analyzed prospectively with reference to clinical and investigative findings before and after exposure to a neuroleptic. The series comprised eight males and nine females, ranging in age from 18 years to 65 years. Prior to neuroleptic exposure, all patients exhibited features compatible with criteria for catatonia (mutism/excitement) according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised, (DSM-III-R). Following neuroleptic administration (single dose in nine cases), patients deteriorated into a febrile, rigid, and obtunded state accompanied by autonomic dysfunction and raised creatine phosphokinase levels. These features were consistent with a diagnosis of NMS. Neuroleptics were discontinued and supportive medical treatment instituted. Benzodiazepines were beneficial in eight cases in relieving stupor, but bromocriptine and dantrolene were generally ineffective. In all patients diagnosed with NMS in the authors' series, catatonia was an invariable prodromal state. It appears that the administration of a neuroleptic intensified the preexisting catatonic state and precipitated a malignant variant of the disorder, which is currently recognized as NMS. The authors, therefore, challenge the separate nosological status of NMS and catatonia and suggest that these syndromes are part of a unitary pathophysiological disorder.     

Lithium therapy for mania and depression

The literature on lithium carbonate was reviewed for clues to the processes involved in mania. Lithium has proved effective therapeutically and prophylactically for mania and depressive disorders. Children and adolescents as well as adults tolerate lithium well. Side effects rarely are serious enough to necessitate having lithium therapy. Some success with schizophrenia and schizoaffective disorders has broadened the scope of lithium's therapeutic efficacy but also blunted the expectation for a direct relationship between lithium and the processes involved in mania. Research points to neurotransmitters as contributing to the etiology and symptom pattern of mania.     

Progressive catatonia

We present the case of a young man with a diagnosis of a childhood-onset pervasive developmental disorder who developed a progressive neurologic deterioration with persistent catatonia and right hemiparesis. On his initial evaluation approximately three years after the onset of mutism, he manifested right hemiparesis and catalepsy. Two years later, although catalepsy had subsided, motor function had deteriorated so that he could not use his hands to feed or dress himself. Oral-facialbuccal dyskinesia manifested by blepharospasm and grimacing were present constantly during waking hours. Quantitative electroencephalography demonstrated markedly decreased amplitude, a finding associated with catatonia. Left sural nerve biopsy indicated large axon cylinder degeneration. Left deltoid biopsy demonstrated perimysial fibrosis and type II fiber predominance. Although magnetic resonance imaging of the head without contrast was normal, positron emission tomography indicated hypometabolism of the right cerebral and the right cerebellar hemispheres. The patient continues to deteriorate despite a course of 25 electroconvulsive treatments. He continues to manifest criteria for catatonia including motoric immobility, mutism, and peculiarities of voluntary movement such as prominent grimacing. We suspect an inherited neurodegenerative disorder. Since catatonia is a treatable condition frequently associated with medical and neurological diseases, examination for the features of catatonia must be included in the assessment of patients with progressive brain degeneration. This report is an attempt to clarify the traits of a serious variant of progressive brain degeneration.     

Treatment of acute mania

Mood stabilizers have evolved considerably over the past decade. Lithium, divalproex, and olanzapine are currently Food and Drug Administration-approved for the treatment of acute mania. A number of new and traditional medications have also been tested and are commonly used in clinical practice. Several strategies for managing treatment-resistant mania have been suggested, but few have been rigorously tested. Emphases on rapid stabilization and fewer side effects have raised the bar for what is expected from mood stabilizers and the successful treatment of mania involves a delicate balance between swiftness, short-term tolerability, and long-term safety.     

Temporal experience in mania

The paper examines both the phenomenology of the manic self as well as critical aspects of manic neurobiology, focusing, with respect to both domains, on manic temporality. We argue that the distortions of lived time in mania exceed mere acceleration and are fundamental for manic affectivity. Mania involves radical acceleration and radical asynchronicity, which result in an instantaneous existence. People with mania rebel against the facticity of reality and suffer from an existential leap towards the future, in which the self abandons normal temporal boundaries. Excerpts from the interviews with persons with mania who experienced psychosis illustrate this phenomenon. Commenting upon disrupted circadian rhythms in mania and the role of lithium in its treatment the paper posits manic temporality as the link through which manic phenomenology and manic neurobiology intertwine.     

Loading strategies in acute mania

Treatment of acute mania has been greatly influenced by loading strategies. Loading has potential benefits, including rapid symptom reduction in mania and a shortened length of stay. Disadvantages include an increased likelihood of adverse effects of the medications. Loading strategies for lithium, valproic acid (divalproex sodium), carbamazepine, oxcarbazepine, olanzapine, and haloperidol decanoate in the treatment of acute mania are discussed. Recent studies highlight this treatment option for selected patients. It is the unique properties of the medications that influence their use in loading. Issues in patient selection for loading strategies with each medication are also considered.     

A Family Therapist's Guide to Bipolar III: Antidepressant-Induced Mania or Hypomania

This article explores the phenomenon of hypomania and mania induced by the treatment with antidepressants, sometimes called bipolar III. Family therapists need to be aware of this phenomenon because estimates are that between 3–10% of depressed individuals may be at risk for developing hypomania or mania when treated with antidepressants. The article discusses implications for family therapists, including their role in the prevention and early detection of antidepressant-induced mania or hypomania.     

GENIUS AND MADNESS?

Abstract— Much evidence has been adduced to support the view, originally proposed by Kraepelin, that mania increases creativity Examples of supporting evidence are findings of similarity in thought between creative persons and manic-depressives and high creativity in normal relatives of manic-depressives However, such data are correlational and are therefore equivocal concerning the hypothesis that mania is a cause of increased creativity The present study analyzed the relationship between mood and productivity in the career of composer Robert Schumann, who has been diagnosed as bipolar Schumann's positive mood was related to increased quantity of his work but not to increased quality, indicating that mania did not increase creativity of thought processes.     

What catatonia can tell us about "top-down modulation": a neuropsychiatric hypothesis

Differential diagnosis of motor symptoms, for example, akinesia, may be difficult in clinical neuropsychiatry. Symptoms may be either of neurologic origin, for example, Parkinson's disease, or of psychiatric origin, for example, catatonia, leading to a so-called "conflict of paradigms." Despite their different origins, symptoms may appear more or less clinically similar. Possibility of dissociation between origin and clinical appearance may reflect functional brain organisation in general, and cortical-cortical/subcortical relations in particular. It is therefore hypothesized that similarities and differences between Parkinson's disease and catatonia may be accounted for by distinct kinds of modulation between cortico-cortical and cortico-subcortical relations. Catatonia can be characterized by concurrent motor, emotional, and behavioural symptoms. The different symptoms may be accounted for by dysfunction in orbitofrontal-prefrontal/parietal cortical connectivity reflecting "horizontal modulation" of cortico-cortical relation. Furthermore, alteration in "top-down modulation" reflecting "vertical modulation" of caudate and other basal ganglia by GABA-ergic mediated orbitofrontal cortical deficits may account for motor symptoms in catatonia. Parkinson's disease, in contrast, can be characterized by predominant motor symptoms. Motor symptoms may be accounted for by altered "bottom-up modulation" between dopaminergic mediated deficits in striatum and premotor/motor cortex. Clinical similarities between Parkinson's disease and catatonia with respect to akinesia may be related with involvement of the basal ganglia in both disorders. Clinical differences with respect to emotional and behavioural symptoms may be related with involvement of different cortical areas, that is, orbitofrontal/parietal and premotor/motor cortex implying distinct kinds of modulation--"vertical" and "horizontal" modulation, respectively.     

Unique association of approach motivation and mania vulnerability

Bipolar disorder involves experiences of both mania and depression over time, and measures of mania-risk and depression-risk therefore tend to be correlated, making it difficult to disentangle the shared versus unique aspects of mania and depression vulnerability. In theory, strong approach motivation is uniquely linked with mania risk, but this relation tends to be obscured unless co-occurring depression risk is statistically controlled. In this study, 461 college students completed the General Behaviour Inventory (GBI)—a validated questionnaire of bipolar disorder vulnerability—and they reported their degree of approach motivation in response to four vignettes that varied in relative incentive versus threat strength. After controlling for the effect of depression vulnerability, mania vulnerability was associated with approach motivation, particularly in response to more threatening scenarios, and this association remained significant even when controlling for dispositional threat and incentive responsiveness, current symptoms, mood, self-esteem, and optimism. The results are consistent with models that regard heightened approach motivation as a unique aspect of mania vulnerability.     

Feeling stuck in the present? Mania proneness and history associated with present-oriented time perspective

Humans have the ability to mentally time travel through past, present, and future. But can a disruption in emotion characteristic of emotional disorders cause this ability to unwind, leaving people "stuck" in the present emotional moment? Two studies are presented that examine emotional time-perspective in a disorder (mania) characterized by present-oriented tendencies, including impulsivity and emotion dysregulation. In Study 1, associations were reported between mania proneness and emotion time-perspective (n = 509), and Study 2 compared emotion time-perspective between individuals with a clinical history of mania (n = 32), and controls (n = 30). We show that mania is associated with increased present and decreased future focus. These findings suggest that emotional disorders can be understood, at least in part, by examining how people understand and use time to guide their behavior and feelings.     

The Mania of Existence: Klein,Winnicott, and Heidegger's Concept of Inauthenticity

This paper offers a new interpretation of Heidegger's concept of inauthenticity (Uneigentlichkeit) in Being and Time. It breaks from the “conformity interpretation” of inauthenticity, according to which the anonymity of the inauthentic person is due to her conformity to das Man. Rather, it argues that the anonymity of the inauthentic person is due to “existential mania” – a state in which a person denies her death and anxiety, understands her abilities to be limitless, and is perpetually active. It shows how this existential mania – and the anonymity to which it gives rise – is analogous to the mania described by the object relations psychoanalyst Melanie Klein. Finally, drawing on D. W. Winnicott's discussion of mania, it shows how both the inauthentic person's conformity to das Man, and her existential mania, give rise to anonymity.