New anticonvulsant medication uses in bipolar disorder

Therapy of bipolar disorders is a rapidly evolving field. Lithium has efficacy in classic bipolar disorders whereas divalproex sodium and carbamazepine may have broader spectrum efficacy that includes non-classic bipolar disorder. In the last 10 years, a series of anticonvulsants have been approved for marketing in the United States. Gabapentin has indirect g-aminobuytric acid-ergic actions, is generally well tolerated, and appears to have anxiolytic, analgesic, and hypnotic effects. Lamotrigine has antiglutamatergic actions and is generally well tolerated (aside from rash in 1 in 10, and serious rash in 1 in 1,000 patients). Lamotrigine is indicated for maintenance treatment in bipolar disorder. Emerging evidence suggests lamotrigine may have utility in bipolar disorder patients with depression and treatment-refractory rapid cycling, as well as analgesic effects. Topiramate and zonisamide may allow both weight loss, while topiramate may have specific efficacy in bulimia, binge eating disorder, and alcohol dependence. Two small studies found oxcarbazepine had similar efficacy to lithium and haloperidol in acute mania. Phenytoin, an older anticonvulsant, may have adjunctive acute mania efficacy. Levetiracetam, a newer anticonvulsant, may be worth exploring and has minimal drug-drug interactions. None of these newer agents has been shown effective in a large placebo controlled trial for acute mania. Although the clinical profiles of these newer anticonvulsants do not appear to overlap markedly with divalproex and carbamazepine (except perhaps for oxcarbazepine), these novel agents may still offer important new options in relieving a variety of specific target symptoms in patients with bipolar disorder.     

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.     

Decision making and neuropsychiatry

Abnormal decision making is a central feature of neuropsychiatric disorders. Recent investigations of the neural substrates underlying decision making have involved qualitative assessment of the cognition of decision making in clinical lesion studies (in patients with frontal lobe dementia) and neuropsychiatric disorders such as mania, substance abuse and personality disorders. A neural network involving the orbitofrontal cortex, ventral striatum and modulatory ascending neurotransmitter systems has been identified as having a fundamental role in decision making and in the neural basis of neuropsychiatric diseases. This network accounts for the dissociations among decision-making deficits in different clinical populations. Ultimately, a more refined and sophisticated characterization of such deficits might guide the early diagnosis and cognitive and therapeutic rehabilitation of these patients.     

Cognitive responses to failure and success relate uniquely to bipolar depression versus mania

This project examined cognitive responses to failure and success and their association with depression and mania within bipolar disorder. Many cognitive variables that are associated with unipolar depression have been found to be involved in bipolar disorder, more specifically bipolar depression. This research was the first to examine tendencies to hold high standards, engage in self-criticism, and generalize from failure to an overall sense of self-worth. In Study 1, undergraduates were screened for risk of mood disorders and completed structured diagnostic interviews. History of bipolar spectrum disorders and history of depression had separate associations with negative generalization. The association of generalization with bipolar spectrum disorders was accounted for by current depressive symptoms. For Study 2, the authors developed a measure of the tendency to engage in positive generalization following success experiences. In a sample of 276 undergraduates, this measure related uniquely to risk for mania. Results of these 2 studies suggest that responses to failure are associated with a history of depression, whereas responses to success are associated with a risk for mania. Implications for future research and clinical work are discussed.     

Role of Reward Sensitivity and Processing in Major Depressive and Bipolar Spectrum Disorders

Since Costello’s (1972) seminal Behavior Therapy article on loss of reinforcers or reinforcer effectiveness in depression, the role of reward sensitivity and processing in both depression and bipolar disorder has become a central area of investigation. In this article, we review the evidence for a model of reward sensitivity in mood disorders, with unipolar depression characterized by reward hyposensitivity and bipolar disorders by reward hypersensitivity. We address whether aberrant reward sensitivity and processing are correlates of, mood-independent traits of, vulnerabilities for, and/or predictors of the course of depression and bipolar spectrum disorders, covering evidence from self-report, behavioral, neurophysiological, and neural levels of analysis. We conclude that substantial evidence documents that blunted reward sensitivity and processing are involved in unipolar depression and heightened reward sensitivity and processing are characteristic of hypomania/mania. We further conclude that aberrant reward sensitivity has a trait component, but more research is needed to clearly demonstrate that reward hyposensitivity and hypersensitivity are vulnerabilities for depression and bipolar disorder, respectively. Moreover, additional research is needed to determine whether bipolar depression is similar to unipolar depression and characterized by reward hyposensitivity, or whether like bipolar hypomania/mania, it involves reward hypersensitivity.     

Spatial and Selective Attention in the Cerebral Hemispheres in Depression, Mania, and Schizophrenia

Two tachistoscopic tests examining distinct aspects of attention were administered to normal subjects and patients with depression, mania, and schizophrenia. The first examined spatial attentional bias using happy-sad chimeric faces, known to elicit a perceptual bias to the left side of space in normal right-handers provided the right cerebral hemisphere is intact. The second used a lateralized version of the Stroop task, a traditional test of selective attention. Normals showed the expected leftward perceptual bias but showed equivalent susceptibility to the Stroop effect in both visual fields. As previously demonstrated with chimeric faces viewed in free vision, depression and mania were associated with weak and strong biases respectively with schizophrenics showing no bias to either side of space. The relationship between perceptual bias, as assessed by reaction time and absolute performance and the Stroop effect, showed differences according to diagnosis. This may be interpreted as evidence for the dissociability of attentional processes as well as lateralized differences in the pattern of cerebral activation in affective disorders and schizophrenia. The independence of performance variables on these tests in the schizophrenic group points to severe neuropsychological dysfunction.     

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.     

The Aftermath of Romantic Betrayal: What’s Love Got to Do with It?

Approaches to love were explored to determine links to psychological experiences after romantic betrayal. Results indicated that the mania (obsessive) love style predicted post-betrayal trauma reactions, depression, and psychosomatic symptoms, whereas other styles were unrelated to these post-betrayal reactions. Weaker effects also were observed in which the mania style was related to post-betrayal anxiety and embarrassment, as well as low levels of psychological resolution for the betrayal across time among those who were no longer involved with their betrayers.     

Consequences of right cerebrovascular accident on emotional functioning: diagnostic and treatment implications

The relationship between lesion location and neuropsychiatric sequelae in stroke patients has been extensively studied. Emotional disorders associated with right hemisphere stroke include depression, anxiety, anger, and/or mania. Pharmacotherapy, electroconvulsive therapy, and/or psychotherapy are common treatments for these disorders. This article reviews the clinical presentations of seven right hemisphere stroke patients. The treatment rationale and course of treatment are described for two of these patients. The aims of this paper are to explore the appropriateness of various assessment tools and treatment modalities for stroke patients as well as to demonstrate the techniques of psychotherapy as applied to the two cases featured in this article. Specific factors that may significantly influence treatment outcome, such as lesion location and degree of cognitive impairment, are considered.     

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.     

Update: new uses for lithium and anticonvulsants

Anticonvulsants are being used clinically as monotherapy and adjuncts in mental illnesses other than affective disorders. This review focuses on the literature for anticonvulsants and lithium in substance use disorders, anxiety disorders, and schizophrenia. Given the abuse potential and other difficulties with prescribing benzodiazepines for alcohol and benzodiazepine withdrawal, anticonvulsants have been considered as an alternative. Promising therapeutic effects have been demonstrated in many of the anxiety disorders, with the greatest number of trials and positive results in posttraumatic stress disorder. Although anticonvulsant and lithium augmentation for schizophrenia is common in practice and has been studied in double-blind, randomized, controlled trials, the sum of the evidence has been inconclusive.     

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.     

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.     

Catatonia in affective disorder: new findings and a review of the literature

The historical development of the concept of catatonia in affective disorders and contemporary papers on this topic are reviewed. In addition, data from a current study on the frequency of catatonia in mixed mania are reported. Differences between catatonic and noncatatonic patients with mixed mania are presented and their relevance to clinical practice is discussed.     

Epigenetics in the mature mammalian brain: effects on behavior and synaptic transmission

The role of epigenetic mechanisms in control of gene expression during mammalian development is well established. Associations between specific DNA or histone modifications and numerous neurodevelopmental and neurodegenerative disorders implies significant consequences of epigenetic dysregulation in both the developing and mature brain, the latter of which is the general focus of this review. Accumulating evidence suggests that epigenetic changes are involved in normal cognitive processes in addition to neurological and psychiatric disorders. Recent investigations into the regulation of epigenetic modifications in the adult brain have revealed novel and surprisingly dynamic mechanisms for controlling learning and memory-related behaviors as well as long-term synaptic plasticity. DNA methylation and histone acetylation have also been implicated in the modulation of basal synaptic transmission and the balance between excitation and inhibition in various brain regions. Studies have begun to uncover some of the alterations in gene expression that appear to mediate many of these effects, but an understanding of the precise mechanisms involved is still lacking. Nevertheless, the fundamental importance of epigenetic processes in influencing neuronal activity is becoming increasingly evident.     

Risk for mania and positive emotional responding: too much of a good thing?

Although positive emotion research has begun to flourish, the extremes of positive emotion remain understudied. The present research used a multimethod approach to examine positive emotional disturbance by comparing participants at high and low risk for episodes of mania, which involves elevations in positive emotionality. Ninety participants were recruited into a high or low mania risk group according to responses on the Hypomanic Personality Scale. Participants' subjective, expressive, and physiological emotional responses were gathered while they watched two positive, two negative, and one neutral film clip. Results suggested that participants at high risk for mania reported elevated positive emotion and irritability and also exhibited elevated cardiac vagal tone across positive, negative, and neutral films. Discussion focuses on the implications these findings have for the diagnosis and prevention of bipolar disorder, as well as for the general study of positive emotion.     

Portability of a screener for pediatric bipolar disorder to a diverse setting

Robust screening measures that perform well in different populations could help improve the accuracy of diagnosis of pediatric bipolar disorder. Changes in sampling could influence the performance of items and potentially influence total scores enough to alter the predictive utility of scores. Additionally, creating a brief version of a measure by extracting items from a longer scale might cause differential functioning due to context effects. The authors of current study examined both sampling and context effects of a brief measure of pediatric mania. Caregivers of 813 youths completed the parent-reported version of the General Behavior Inventory (PGBI) at an academic medical center sample enriched for mood disorders. Caregivers of 481 youths completed the PGBI at a community mental health center. Caregivers of 799 youths completed 10 items extracted from the PGBI at a community setting. Caregivers of 159 youths completed both versions of the PGBI and a semistructured diagnostic interview. Differential item functioning indicated that across samples some items functioned differently; however, total observed scores were similar across all levels of mania. Receiver operating characteristic analysis indicated that the 10 extracted items discriminated bipolar disorder from nonbipolar behavior as well as when the items were embedded within the full measure. Findings suggest that the extracted items perform similarly to the embedded items in the community setting. Measurement properties appear sufficiently robust across settings to support clinical applications.     

Assessing the dysregulation of the Behavioral Activation System: the Hypomanic Personality Scale and the BIS-BAS scales

We discuss the Hypomanic Personality Scale (Hyp; Eckblad & Chapman, 1986) and the Behavioral Inhibition System (BIS-BAS; Carver & White, 1994) and Behavioral Activation System (BAS; Gray, 1991) Scales as risk factors for bipolar disorders. The dysregulation of the BAS is considered to be central and results in higher variability in mood. Therefore, we examined how those scales are associated with mood fluctuations. A total of 59 participants completed a diary for at least 17 days. It included a modified Center for Epidemiologic Studies-Depression Scale (Meyer & Hautzinger, 2001) assessing depression and mania and the Positive and Negative Affect Schedule (Watson, Clark, & Tellegen, 1988). Hyp and BAS predicted levels of mania and of positive affect but also fluctuations of mania. Hyp also predicted instability of negative affect. Our data also suggest that mood variability is a trait-like feature. Both scales seem not to be perfect measures of the dysregulation factor. Future research should assess this dysregulation more directly.