Sullivan / DeRemer Sullivan Biomedical Psychiatric Therapeutics

1. Auflage 2013
ISBN: 978-1-4831-9270-3
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 292 Seiten

Biomedical Psychiatric Therapeutics presents the basic principles of biomedical psychiatric therapeutics. It discusses special areas of major clinical importance where biomedical psychiatry connects with chemical dependencies. It addresses the advances in biological exploration of psychiatric disorders that have a major impact on biomedical psychiatric therapeutics. Some of the topics covered in the book are the chemotherapy of anxiety; treatment of alcohol withdrawal; use of anxiolytics in patients with medical illness; chemotherapy of affective disorders; monoamine oxidase inhibitors; atypical antidepressants; indications for lithium therapy; and treatments for manic-depressive disease. The chemotherapy of schizophrenia is fully covered. The electroconvulsive therapy is discussed in detail. The text describes in depth the systemic morbidity and mortality. The effect of electroconvulsive therapy in the central nervous system is presented completely. A chapter is devoted to the use of the clinical laboratory. Another section focuses on the chromosomal abnormalities. The book can provide useful information to psychologists, doctors, students, and researchers.

Autoren/Hrsg.

Sullivan, John L

DeRemer Sullivan, Paula

Leseproben

CHAPTER 1

Chemotherapy of Anxiety

John L. Sullivan, Paula D. Sullivan, Steve Mahorney and Richard L. Goldberg

Publisher Summary

This chapter discusses anxiety and its general treatment approaches. Anxiety can be viewed as an adaptive mechanism that has survival value if it falls within a normative range. Anxiety reflects a complex emotional response to a variety of human circumstances. It is generally regarded as an unpleasant feeling that is similar in certain respects to fear. At pathologic levels, anxiety reflects an emotional response to danger that is disproportionate to the objective degree of the threat, and the psychophysiologic manifestations of anxiety may resemble extreme fear and panic. The development of medicinals to treat pathologic anxiety constitutes a major contribution to 20th century psychiatry. Although there are still important questions to be answered regarding the most effective utilization of anxiolytics in clinical practice, general guidelines have been developed to significantly reduce abuse and potential toxicity of these compounds. Furthermore, advances in the understanding of the neurochemical mechanism of action of anti-anxiety agents and the metabolic basis of anxiety promise to productively increase the understanding of the interrelationships between brain function and behavior. Although the various benzodiazepines are currently considered to be most effective for treating pathologic anxiety in a variety of settings, specific uses have been proposed for heterocyclic antidepressants, monoamine oxidase inhibitors, ß-blockers, antihistamines, and, perhaps, neuroleptics, and clonidine to increase the specificity and sensitivity of the therapeutic armamentarium. Other than that, work with other classes of compounds that demonstrate anxiolytic properties such as thiazolopyridazines and azaspirodecanediones continues to refine the ability to provide effective and safe chemotherapy for the anxiety disorders.

The nature and meaning of anxiety have provided an issue for speculation, observation, and experimentation since the earliest periods of civilization. Normal anxiety is often considered to be a warning signal that serves to protect psychobiologic functioning. However, for reasons that are poorly understood, anxiety can reach dimensions that threaten the integrity of psychobiologic functioning and thus constitute a pathologic condition. For example, adaptive as well as creative behaviors appear to be more successful if there is an optimal element of anxiety, but pathologic anxiety can incapacitate such behaviors to the extent that they become ineffective. Anxiety stems from anticipation of impending danger in which the source and character of the danger cannot be clearly defined, whereas fear is an emotional reaction to a specific and known danger (1). Both of these emotional reactions are responses to organismic stress. Thus, anxiety can be viewed as an adaptive mechanism that has survival value if it falls within a normative range.

Anxiety itself reflects a complex emotional response to a variety of human circumstances. It is generally regarded as an unpleasant feeling that is similar in certain respects to fear. At pathologic levels, anxiety reflects an emotional response to danger that is disproportionate to the objective degree of the threat, and the psychophysiologic manifestations of anxiety may resemble extreme fear and panic. Because anxiety is a phenomenon which is often difficult to evaluate and quantify, exact figures about its prevalence and magnitude within any given social group are difficult to obtain. In large measure, we must rely on subjective reports of anxiety, since there are few widely accepted and objectively verifiable composite measures for the phenomenon. A number of self-rating and observer-rating tests that measure specific, subjective impressions, and behavioral variables have been designed to quantify some of the more commonly agreed upon manifestations of anxiety.

A distinction that has gained some popularity in recent years is the differentiation between state anxiety and trait anxiety. State anxiety concerns an emotion felt at a given time in response to a specific circumstance or set of circumstances, whereas trait anxiety refers to a personal characteristic of an individual, including a baseline of anxiety and susceptibility to anxiety in response to stress. According to this concept, state anxiety can be superimposed on trait anxiety, and the results of treatment may vary in these two types. Although this concept of anxiety has theoretical implications, the evaluation of potentially therapeutic agents that are effective in alleviating anxiety (anxiolytics) relies in large measure on the determination of generally excessive anxiety at the time of treatment.

The central role of anxiety in subjective and objective human behaviors states has been appreciated for millenia by philosophers, but Sigmund Freud was the first to attempt to explain anxiety in scientific terms. Freud conceived that anxiety was fundamentally composed of inherited biologic factors that were influenced significantly by developmental and social factors, and that perturbations in any or all of these systems could result in pathologic anxiety, as manifested in a variety of psychopathologic states. Unfortunately, much of Freud’s work remained in the theoretical realm during his lifetime because of the relative technical inadequacies of psychobiologic inquiry that prevailed during his lifetime.

The notion that anxiety can be conceptualized as a functional state subject to maladaptive influence suggests that abnormal anxiety may result in symptomatic disease states in much the same way that adrenal tumor or cardiogenic shock may result in hypertension or hypotension, respectively. Most of the knowledge that we have acquired about the phenomenon of pathologic anxiety has emphasized the consequences of excessive amounts of anxiety. Therefore, the development of medicinals to treat pathologic anxiety has focused on pharmacologic compounds that serve as effective antianxiety agents.

BENZODIAZEPINES

Benzodiazepines are considered to be the most effective class of medicinals for the treatment of anxiety, except perhaps, for separation anxiety associated with panic attacks and the phobic-anxiety syndrome, which are discussed later (1). Since the introduction of benzodiazepines for clinical use, there has been a marked increase in the prescription of anxiolytics. For the past decade, the benzodiazepines, particularly diazepam and chlordiazepoxide, have been among the most frequently administered prescription drugs in the United States, as well as in many other countries throughout the world. It is interesting that the majority of prescriptions for these anxiolytics is written by non-psychiatrists and that fewer than half of the prescriptions are dispensed to patients with a formal psychiatric diagnosis.

An important neurochemical mechanism associated with the anxiolytic properties of benzodiazepines appears to be facilitation of chemical transmission in the central nervous system’s gamma aminobutyric acid (GABA -ergic) neuronal system. Starting in 1977, a number of research groups independently demonstrated the existence of very specific central nervous system binding sites for benzodiazepines on brain membranes. Research indicates that this benzodiazepine receptor is, in fact, the GABA receptor—a supramolecular structure with two recognition sites (2). GABA binds to one site and benzodiazepines bind to the second site. GABA, the neurotransmitter of about 30 percent of the neurons in the brain, has long been recognized as the most important inhibitory neurotransmitter in the brain; it is known to act on all areas of the central nervous system to inhibit neuronal firing. Anxiety is probably associated with hyperexcitability of certain neural pathways—that is, an excessive neural firing rate. When a benzodiazepine is administered, the drug binds to its site on the GABA receptor, enhancing the binding of GABA and potentiating its effect.

Other studies have also identified several compounds, the purines inosine and hypoxanthine and nicotinamide, that competitively inhibit the binding of (3H) diazepam and that may function as naturally occurring antianxiety substances, or endogenous benzodiazepines. These findings correlate with animal studies that have shown potential anxiolytic properties for a new class of purinelike agents, the thiazolopyridazines (1,2).

Dosage Ranges

Dosage ranges (mg/day) for the most frequently used benzodiazepines in clinical practice are given in Table 1.1. Although no significant tolerance usually develops to their anxiolytic properties, tolerance often develops to sedating and other central nervous system effects of the benzodiazepines. Therefore, physicians should counsel their patients to approach important decisions and complex motor functions with particular caution when benzodiazepine treatment is initiated and when there is an upward adjustment in dosage. When benzodiazepine treatment is initiated, side effects can often be minimized with a divided dose schedule in which two-thirds of the dose is given one or two hours before bedtime and the remainder is given once or twice during the day. With this type of a regimen, the initial sedative-hypnotic properties of the benzodiazepines can also be maximized. Although there is no pharmacokinetic rationale to support continuation of such a regimen for a prolonged period of time, some individuals...