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.     

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.     

Reassessing carbamazepine in the treatment of bipolar disorder: clinical implications of new data

This monograph summarizes the proceedings of a roundtable meeting convened to discuss the role of carbamazepine in the treatment of bipolar disorder, in light of new data and the recent indication of carbamazepine extended-release capsules (CBZ ERC) for use in the treatment of acute manic and mixed episodes. Two lectures were presented, followed by a panel discussion among all 6 participants. A summary of the two pivotal trials of CBZ ERC and their pooled data along with other relevant data is presented first. Next, historical trends of carbamazepine and the agent's use in acute mania, bipolar depression, and maintenance are reviewed, emphasizing clinical implications of efficacy, safety, tolerability, and drug interactions. Finally, the panel discussion provides recommendations for the use of carbamazepine in different phases of the illness, taking into account adverse effects and drug-drug interactions. Panel discussants agree that current data confirm the utility of CBZ ERC as an effective treatment for acute manic and mixed episodes in bipolar disorder. Carbamazepine may also prove to be an option for maintenance treatment. Tolerability of the drug is related to dose and titration, and overall safety limitations regarding carbamazepine usage are comparable to other medications. For some patients, the main challenges to use of carbamazepine may be common drug-drug interactions and increased side effects related to aggressive introduction during treatment of acute manic and mixed episodes. Thus, carbamazepine may be a lower priority option for patients who are taking multiple medications, such as elderly individuals with medical comorbidity, due to the potential for drug interactions. Important benefits of carbamazepine include the low propensity toward weight gain and evidence of good tolerability with long-term treatment. (At present there are no available data from long-term, placebo-controlled studies evaluating the effects of carbamazepine or CBZ ERC on weight.) Thus, carbamazepine may be a good option for patients who are concerned about weight gain or who are intolerant of or respond poorly to other medications. Further efforts are needed to update physicians on the use of carbamazepine relative to other medications in the treatment of bipolar disorder.     

The "good enough" mood stabilizer: a review of the clinical evidence

A growing family of medications is used for mood stabilization in bipolar disorder. These medications fall into two broad categories according to likely mechanisms of action. Within the categories, specific drugs may vary in their efficacy for different phases of the disorder. The first category, including lithium, anticonvulsants, and some novel treatments, appears to have mechanisms related to intracellular second messengers. These medications have more pronounced antimanic than antidepressant effects, except for lamotrigine, which has antidepressant effects without precipitating mania. The second group of mood stabilizers is the atypical antipsychotics, which act through dopamine and other monoamines. Olanzapine and in all likelihood other drugs in the class possess marked, acute antimanic properties and possible antidepressant properties, but require further study before they can be used as routine options in long-term care. It is clear that the advent of multiple mood stabilizer candidates has not yet led to a single ideal therapy for bipolar disorder, but rather to options that can be flexibly tailored to the lifetime needs of individual patients, in sequences or combinations, and perhaps in conjunction with other classes of psychotropics.     

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.     

Pharmacologic Treatment of Attention-Deficit/Hyperactivity Disorder: Efficacy,Safety and Mechanisms of Action

Studies examining the efficacy, safety and mechanisms of action of agents for the treatment of attention-deficit/hyperactivity disorder (ADHD) are reviewed, with an emphasis on newer agents such as the long acting stimulants and atomoxetine. Recent studies of medications are characterized by large, rigorously diagnosed samples of children, adolescents and adults with ADHD, use of standardized rating scales and extensive safety data. These studies confirm a robust treatment effect for the Food and Drug Administration approved agents ranging from 0.7 to 1.5. The most common short term side effects to the most commonly used agents include insomnia, loss of appetite, and headaches. Despite public controversy and labeling changes to warn of extremely rare cardiovascular and psychiatric side effects, the evidence does not support the hypothesis that medication for ADHD increases risk for sudden death, mania or psychosis. A wide variety of neuroimaging techniques including electrocephalogram (EEG) power, event related potentials (ERP), functional magnetic resonance imaging (fMRI), and positron emission tomography (PET) are beginning to examine the mechanisms of action of medications for ADHD, and implicating the catecholamines and prefrontal and anterior cingulate cortices as prime sites of actions for these agents.     

Manic temporality

Time-consciousness has long been a focus of research in phenomenology and phenomenological psychology. We advance and extend this tradition of research by focusing on the character of temporal experience under conditions of mania. Symptom scales and diagnostic criteria for mania are peppered with temporally inflected language: increased rate of speech, racing thoughts, flight-of-ideas, hyperactivity. But what is the underlying structure of temporal experience in manic episodes? We tackle this question using a strategically hybrid approach. We recover and reconstruct three hypotheses regarding manic temporality that were advanced and modeled by two pioneers of clinical phenomenology: Eugène Minkowski (1885–1972) and Ludwig Binswanger (1881–1966). We then test, critique, and refine these hypotheses using heterophenomenological methods in an interview-based study of persons with a history of bipolar and a current diagnosis of acute mania. Our conclusions support a central hypothesis due to Minkowski and Binswanger, namely, that disturbance in the formal structure of temporal experience is a core feature of mania. We argue that a suitably refined variant of Binswanger’s model of disturbance in manic protention helps to explain a striking pattern of impaired insight and impaired reasoning in manic episodes.     

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.     

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.     

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.     

Clinical perspectives on the combination of D-cycloserine and cognitive-behavioral therapy for the treatment of anxiety disorders

In a particular success for translational research agendas, characterization of the neuronal circuits underlying fear extinction, and basic research in animal extinction paradigms, has led to intervention studies examining the use of D-cycloserine (DCS) to enhance therapeutic learning from exposure-based cognitive-behavioral therapy (CBT). In this article, we review these intervention studies, and discuss DCS augmentation of CBT relative to more traditional combination-treatment strategies in the treatment of anxiety disorders. We offer an accounting, based on evidence for internal context effects, of current limitations in the combination of antidepressant or benzodiazepine medications with CBT and discuss the advantages of isolated-dosing strategies with DCS relative to these limitations. This strategy is contrasted with the chronic-dosing applications of DCS for schizophrenia and Alzheimer's disease, and future directions for isolated-dosing strategies are discussed.     

Pharmacologic treatment of schizophrenia: what the future holds

The advent of the newer "atypical" antipsychotics has revolutionized pharmacologic treatment of schizophrenia (SZ) and other psychotic disorders. In contrast to the first-generation conventional neuroleptics, these second-generation antipsychotic agents possess a broader spectrum of efficacy and cause fewer motor side effects such as extrapyramidal symptoms and tardive dyskinesia. Despite their substantial advantages, however, these second-generation agents also have significant limitations in terms of both efficacy and adverse effects. Several strategies to address these shortcomings are currently under study and some of these are likely to become part of our therapeutic armamentarium in the future. Current shortcomings in the pharmacologic treatment of SZ and strategies under investigation to address each of these deficiencies are reviewed. New formulations of existing medications and new antipsychotics under development are discussed. Developing adjunctive treatment strategies to address each of the major psychopathologic domains in SZ are summarized. The potential application of genetic information to treatment-matching in SZ is reviewed and likely refinements in the practice of evidence-based medicine in the pharmacotherapy of SZ are considered.     

A factor simplicity index

We propose an index for assessing the degree of factor simplicity in the context of principal components and exploratory factor analysis. The new index, which is called Loading Simplicity, is based on the idea that the communality of each variable should be related to few components, or factors, so that the loadings in each variable are either zero or as far from zero as possible. This index does not depend on the scale of the factors, and its maximum and minimum are only related to the degree of simplicity in the loading matrix. The aim of the index is to enable the degree of simplicity in loading matrices to be compared.The author would like to thank the review team for their insights and recommendations. This work was supported by a grant SEC2001-3821-C05-C02 from the Spanish Ministry of Science and Technology.     

Treatment-resistant posttraumatic stress disorder: strategies for intervention

The mainstay of treatment for chronic posttraumatic stress disorder (PTSD) is a combination of psychotherapy and medication treatments. The first-line medications for PTSD are antidepressants, with two selective serotonin reuptake inhibitors (sertraline and paroxetine) currently Food and Drug Administration-indicated for PTSD. However, many patients do not have an adequate response to antidepressants, therefore, combinations with other antidepressants or with other classes of psychotropic medication are often utilized to enhance the therapeutic response. Other agents that have been used include mood stabilizers, anti-adrenergics, anxiolytics, and atypical antipsychotics. The heterogeneity of symptom clusters in PTSD as well as the complex psychiatric comorbidities (eg, with depression or substance abuse) further support the notion that combinations of medications may be needed. To date, there is a paucity of data to support specific strategies for augmenting antidepressants in PTSD. This review will address representative existing studies and discuss several potential pharmacologic strategies for patients suffering from treatment-refractory PTSD.     

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.     

Effects of loading modes on densification efficiency of spark plasma sintering: sample study of zirconium carbide consolidation

Theoretical studies on the densification kinetics of the new spark plasma sinter-forging (SPS-forging) consolidation technique and of the regular SPS have been carried out based on the continuum theory of sintering. Both modelling and verifying experimental results indicate that the loading modes play important roles in the densification efficiency of SPS of porous ZrC specimens. Compared to regular SPS, SPS-forging is shown to be able to enhance the densification more significantly during later sintering stages. The derived analytical constitutive equations are utilised to evaluate the high-temperature creep parameters of ZrC under SPS conditions. SPS-forging and regular SPS setups are combined to form a new SPS hybrid loading mode with the purpose of reducing shape irregularity in the SPS-forged specimens. Loading control is imposed to secure the geometry as well as the densification of ZrC specimens during hybrid SPS process.     

The Use of Psychoeducation for a Patient with Hepatitis C and Psychiatric Illness in Preparation for Antiviral Therapy: A Case Report and Discussion

The standard of care treatment for chronic hepatitis C viral infection (HCV) is a combination of pegylated interferon alfa and ribavirin for 24-48?weeks according to the virus genotype. This therapy is known to have multiple neuropsychiatric side effects. A major concern when evaluating a patient for HCV treatment with a known history of a psychiatric disorder is the risk that the patient's psychiatric disorder will flare or become unmanageable. The possibility of precipitating depression, confusion, mania, psychosis, hallucinations, or suicidal ideation or attempt is frequently an obstacle to treatment. We present the case of a 50?year-old man with HCV and an extensive psychiatric history involving alcoholism, depression, and suicidality who participated in a psychoeducation group to help prepare him for treatment with pegylated interferon alfa/ribavirin therapy. Though the patient derived much benefit from the psychoeducation group, by the time of evaluation for HCV treatment two months after the group ended he had relapsed back into a depressive episode with suicidal thoughts. His acute psychiatric status made him unacceptable for pegylated interferon alfa/ribavirin therapy. Psychoeducation groups show promise for helping patients with chronic medical illness to be ready for and endure intensive medical treatment that has substantial psychiatric side effects. The challenge is to help patients overcome barriers to treatment, particularly psychosocial problems, because available treatments are increasingly effective.     

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.