Treatment Of Anxiety States Research Articles

A descriptive study of anxiolytic and hypnotic prescribing according to age and sex

Abstract Objective Benzodiazepines are primarily indicated for the treatment of anxiety states and as hypnotics. Their inappropriate use often relates to duration and manner of use. Few studies have attempted to assess the prevalence of benzodiazepine prescribing in South Africa. The primary aim of the study was to examine the prevalence of sedative/hypnotic prescribing according to patient age and sex in a primary care setting. Setting South African private healthcare patients. Method An exposure cohort drug utilisation study was conducted. Prescription data were obtained from a South African private medical aid administrator. Descriptive statistics were used in the data analysis. Key findings Prescription records (n = 27 080) of 8084 patients in 2004 who were prescribed one or more benzodiazepines were retrospectively analysed. The average age of patients receiving benzodiazepines was 43.17 years (standard deviation (SD) 14.42 years). Benzodiazepine prescribing was more common in females (55.64% of patients were female). There was an increase in prescriptions per patient with increasing age, peaking at an older age among females. Diazepam (13.36%), zopiclone (13.19%) and oxazepam (12.03%) were the most frequently prescribed active ingredients. The majority of benzodiazepine hypnotics were prescribed in quantities of up to 14 units (tablets or capsules), while the benzodiazepine-related drugs zolpidem and zopiclone were prescribed in quantities of up to 30 units. Anxiolytics were often prescribed in quantities of 20 to 30 units. Conclusion Anxiolytics were prescribed in greater quantities than hypnotics. An increase in anxiolytic/hypnotic prescriptions and quantities of tablets/capsules occurred with increasing age. The trends and differences that were detected in the prescribing of benzodiazepines warrant further investigation in larger patient populations, especially with respect to the choice of agent, duration of treatment and patient age.

Étifoxine, neurostéroïdes et anxiété

Anxiety states are related to the hypofunctioning of GABAergic inhibitory synaptic transmission in certain regions of the encephalon. Benzodiazepines are currently used in the treatment of anxiety states, but they are associated with side effects (sedation, amnesia) and their use in long-term treatment poses problems of functional tolerance. Benzodiazepines bind to specific sites located on the GABA A receptor channels that underlie rapid GABAergic transmission and potentiate their functioning. Neurosteroids such as allopregnanolone that are reduced in positions 3α and 5α (3α5α-NS) also potentiate GABA A receptor function and may be considered as endogenous anxiolytics. Neurosteroids are distinguished from other steroids by the fact that they are synthesised de novo in the nervous system by neurons and glial cells independently of circulating steroids. This synthesis occurs from cholesterol imported into the mitochondrion by a multiprotein complex of which the « peripheral benzodiazepine receptor », recently renamed TSPO (translocator protein of 18 kDa), forms a part. The majority of benzodiazepines bind to this protein and stimulate the transfer of cholesterol and consequently neurosteroidogenesis. These effects can be blocked pharmacologically by PK11195, which acts as an antagonist at the mitochondrial binding site for benzodiazepines. Cholesterol is transformed in the mitochondrion to pregnenolone, the universal precursor of all steroids. Pregnenolone then leaves the mitochondrion and the nature of the steroids synthesised in the cytoplasm will depend on the type of neurosteroidogenesis enzymes expressed by the cell. Etifoxine does not possess a benzodiazepine-related structure but does exhibit anxiolytic effects. The objective of our study consequently was to understand the mechanism of action of this compound by studying its effects on the functional properties of GABA A receptors and on GABAergic synaptic transmission. Binding tests on isolated membranes have revealed that etifoxine binds directly to the GABA A receptor and the peripheral benzodiazepine receptor (TSPO). Electrophysiological experiments have shown that etifoxine dose-dependently potentiates membrane currents induced by the application of submaximal but not of saturating concentrations of GABA. Etifoxine also facilitates GABAergic transmission in hypothalamic neuronal cultures and increases the amplitude of a sustained GABAergic current due to the tonic activation of GABA A receptors by a weak GABA concentration in the extracellular space. The effect of etifoxine on this current is partially antagonised by PK11195 but not by flumazenil, an antagonist of the benzodiazepine binding sites on the GABA A receptor. All of our data indicate that etifoxine facilitates GABAergic inhibition by two types of action: [1] by directly potentiating the activity of GABA A receptors via an allosteric modulatory different site from that of the benzodiazepines, and [2] by stimulating the production of 3α5α-NS, which in turn potentiate the activity of GABA A receptors. These two effects are independent and additive. They therefore contribute to make GABAergic transmission more effective.

Antidepressant-anxiolytic interactions: Involvement of the benzodiazepine-GABA and serotonin systems

1. 1. Recent studies have demonstrated that antidepressant drugs are actually more effective than BZ's in the treatment of anxiety states. The role of two major neurochemical substrates that may be implicated in the anxiolytic activity of antidepressants, the benzodiazepine (BZ)-GABA receptor chloride ionophore complex and central serotonergic pathways, are focused on in this review. 2. 2. A wide range of antidepressants elicit a reduction in BZ receptors and display anxiolytic effects within a conflict paradigm. 3. 3. The anxiolytic activity of antidepressants, however, does not appear to be mediated via the BZ receptor, but possibly via another component of the complex such as the chloride channel-associated with the GABA A receptor. 4. 4. Additionally, as possible candidates for the mechanism of anxiolytic activity of these compounds, results of pharmacological, behavioral and clinical studies point to the importance of serotonin (5-HT) 1A receptors and 5-HT transporter sites as targets for the action of antidepressants, triazolobenzodiazepines and anxioselective piperazine derivatives.

Thymosthenic effects of ritanserin (R 55667), a centrally acting serotonin‐S2 receptor blocker

AbstractRitanserin, characterized as a long‐acting serotonin‐S2 antagonist and as a pure and selective antagonist of LSD discrimination in rats, was found to be effective in the treatment of anxiety states. In these studies the observation that the patients felt less tired and more energetic with improved mood has led to study the effects of ritanserin 10 mg b.i.d. in dysthymic disorder and chronic schizophrenia, two conditions with a predominant symptomatology of anergy. The results obtained from two separate placebo‐controlled studies showed significant improvement of depressive mood, early insomnia, agitation, and psychic anxiety in the dysthymic group, whereas negative and affective symptoms showed the best improvement in the schizophrenic group under concurrent decrease of extrapyramidal symptomatology. In both diagnostic groups the drug treatment was very well tolerated. Based on the results that ritanserin showed predominant improvement of anergy and depressed mood, the drug was ascribed thymosthenic properties, which are further supported by the specific property of ritanserin to increase human slow wave sleep.

The ego activation method: Anin vivo cognitive therapy integrating behavioral and psychodynamic approaches

This article discusses an innovative psychotherapeutic approach, known as the ego activation method, which expedites progress in the treatment of anxiety states and nonbipolar, nonpsychotic, acutely depressed outpatients. The method, readily integrated into approaches of diverse orientations, systematically provides patients with experiences with real problems and risks in the context of the therapy sessions. The sessions consist not simply of a series of “verbal exchanges” but of “verbal exchanges plus actions” with a wide array of specially devised therapeutic tasks — over 200 have been developed. The tasks establish a working alliance between the patient and the therapist, activate ego adaptive processes, and assist the patient in developing mastery and control over his/her problems. The method implements therapeutic success through addressing three active ingredients in the therapeutic process: (1) assisting the patient to assume a more active, assertive role; (2) promoting internal locus of control and self-responsibility; and (3) enhancing the patient's sense of mastery. References to detailed case reports are provided.

Treatment of Anxiety State in Elderly Persons by Behaviour Therapy

Treatment of Anxiety State in Elderly Persons by Behaviour Therapy

A Controlled Comparative Trial of Mianserin and Diazepam in the Treatment of Anxiety States in Psychiatric Out-Patients

Forty psychiatric out-patients with primary anxiety entered a double-blind trial comparing 2 weeks of treatment with mianserin 30--60 mg daily or diazepam 15--30 mg daily, followed by 2 weeks of single-blind placebo administration. Both drugs were effective anti-anxiety agents, but mianserin was significantly superior in efficacy as measured by the Physician's Global Rating of Severity of Illness. No differences between treatments were apparent using the Hamilton Rating Scale for Anxiety. There was no significant differences in terms of side-effects and both drugs increased anticholinergic effects such as dry mouth, blurred vision and constipation over baseline values. With one exception in the mianserin group, all patients who entered placebo treatment became worse.

Propranolol in the treatment of anxiety neurosis

In a double-blind controlled trial the beta-adrenergic blocking agent propranolol at the dose level of 120 mg/day was found to be safe and effective in the treatment of 28 moderately to severely ill chronic anxiety neurosis patients diagnosed and selected according to rigorous and specific criteria. A reduced dose, i.e., 40 mg/day, of propranolol was found to be ineffective. Both univariate and multivariate nonparametric statistics were used in the analysis. Problems such as pathogenetic mechanisms in the production of anxiety symptoms, mode of action of beta blockers and their place in the treatment of anxiety states, optimum dose, monitoring plasma level of the drug, and long-term use have been discussed.

Treatment of anxiety states.

This clinical and theoretical paper discusses the broad areas of similatity and overlap that exist between behavior therapy and psychoanalytically oriented psychotherapy. It opens with a fantasy of the origins of anxiety and of psychotherapy followed by some historical and contemporary definitions from both points of view. A final common pathway of theory and technique is suggested and illustrated with two case vignettes. <b>"Anyone who wants to make a living from the treatment of nervous patients must clearly be able to do something to help them."</b>¹

Anxiety associated with flying: a retrospective survey of military aircrew psychiatric casualties.

This paper describes a retrospective study of the influence of personal variables and treatment methods on the prognosis for a return to flying of service aircrew suffering from anxiety states precipitated by flying stress. The study was made preparatory to a prospective investigation of treatment of anxiety states in aircrew.

Nitrazepam (Ro 4-5360) in the Treatment of Anxiety States. Double Blind Trial

Nitrazepam (Ro 4-5360) in the Treatment of Anxiety States. Double Blind Trial

Oxazepam in the treatment of anxiety states: A controlled study

Twenty-six psychoneurotic inpatients received oxazepam (60–120 mg daily) or placebo for one to two weeks. The strongest evidence for the superiority of oxazepam over placebo was that a greater proportion of oxazepam-treated patients remained on the study the full two weeks than placebo-treated patients. Patients' self-evaluations on the MMPI also favored oxazepam. Behavioral ratings by clinicians and ward personnel on the BPRS, symptom checklist, and assessment of global disorder did not discriminate the active drug from placebo as well as self-ratings did. Most of the differences found favored oxazepam, although some failed to reach acceptable levels of significance. It is suggested that the relative similarity of neurotic individuals to normal individuals with respect to pathology (e.g. anxiety, tension, depression) and difficulties in life and that the subjectivity of experience and the absence of gross and easily demonstrable symptoms make evaluation of improvement difficult. Symptom measurement on behavioral rating devices is probably less effective in discriminating drug-placebo differences in neurotic syndromes than in psychotic syndromes.

Treatment of anxiety states by antidepressant drugs.

Treatment of anxiety states by antidepressant drugs.

Arterial thrombosis with gangrene after use of promazine (sparine) hydrochloride.

This paper is a report of two cases of unusual and remarkably similar complications resulting from intravenous injection of promazine (Sparine) hydrochloride. Promazine, a phenothiazine derivative, is recommended in treatment of anxiety states, somatic disturbance, alcoholic syndromes, drug addiction, psychosis, manic depressive states, and schizophrenia. Many side-reactions have been reported with its use, some mild and some severe. Untoward and catastrophic vascular complications in the two patients with alcoholism reported on here followed intravenous injection of this drug. Lemere, 1 in 1950, warned that further observations are needed to establish the exact role of promazine therapy in intoxicated alcoholics. He reported that in one patient, after several intramuscular injections, promazine caused such a severe local reaction, with marked inflammation and induration at the site of injection, that its use had to be discontinued. He also reported three instances of convulsions after intramuscular administration of promazine in severely intoxicated patients. He

Treatment of anxiety states. II. Clinical trial of benactyzine in anxiety states.

Of all the tranquillizers, it may well be said that benactyzine has had the most chequered history. After its synthesis, a series of most careful experiments on animals demonstrated its ability to reduce or modify behaviour induced by stress. The first clinical trial gave rise to high hopes of its value in treatment but as further trials, more carefully designed, were made the results became increasingly inconclusive.

Treatment of anxiety states. I. The effects of suggestion on the symptoms of anxiety states.

The increasing importance of properly controlled drug trials in modern medicine has shown the need for further study of the “placebo response” and the effects of “suggestion”, particularly in the evaluation of the results of treatment of the psychoneuroses. Much of the work on the response to placebos has been done on their deleterious side-effects, i.e., the production of symptoms of various kinds, but some recent investigations have clearly demonstrated the amelioration of symptoms by the administration of placebo.

Treatment of Anxiety States

The assessment of the results of a treatment in any particular disorder is generally a very complicated one, by reason of the fact that the treatment does not usually improve all the manifestations of the disorder, and even when it does so, it does not affect them equally. The case of thyroid medication, which completely eliminates all the manifestations of thyroid deficiency, is an unusual one in medicine. Even where the pathological process may be completely stopped, as in general paresis and pulmonary tuberculosis, the patient may be left with residual loss of function due to irrevocable loss of normal tissue. In some cases the treatment itself may be of such a nature that the patient merely exchanges one disability for another. For example, the treatment of mild diabetes mellitus by a reducing diet may indeed eliminate the diabetes, but only at the cost of replacing it by chronic hunger and social restrictions, which many patients feel are worse than the original disease. In the end, they may give up their treatment. In some cases, the treatment has “complications”, which means to the patient that he merely exchanges one set of symptoms for another. For example, he may exchange the symptoms of duodenal ulcer for those of dumping syndrome.

Benactyzine as an aid in treatment of anxiety states; preliminary report.

Benactyzine as an aid in treatment of anxiety states; preliminary report.

The value and limitations of chlorpromazine in the treatment of anxiety states.

Chlorpromazine hydrochloride (Largactil) introduced by Laborit (1952) has aroused considerable interest on account of its varied pharmacodynamic actions and clinical reports drawing attention to its possible use in anaesthesia, general medicine and psychiatry.Chemically related to certain antihistamine drugs, it has little antihistaminic activity itself but has diverse effects on the nervous system. It is a neural depressant with central and peripheral action, vagolytic and sympatholytic properties. (Chauchard, 1952; Courvoisier, 1953; Sigwald and Boutier, 1953; Staehelin and Kielholz, 1953; Lehrman and Hanrahan, 1954; Anton-Stephens, 1954; Winkelman, 1954; Garmany, 1954; and Elkes and Elkes, 1954.)Enthusiastic claims have been made regarding the therapeutic value of chlorpromazine in a wide variety of psychiatric disorders; many of these have failed to carry conviction, as most of the reports are based on mixed groups with an insufficient number of patients in each diagnostic category to justify definite conclusions and also because controlled procedures were rarely used.We therefore decided to confine our investigation to one type of psychiatric disorder and chose anxiety states, since the reported pharmacodynamic actions of the drug suggested that it might be of value in the treatment of states of anxiety and tension. The total group studied consists of 150 patients all of whom are treated as out-patients.

The recognition and treatment of anxiety states.

Anxiety states are among the most prevalent conditions with which physicians everywhere have to deal. They are encountered in the form of (1) anxiety neuroses, (2) anxiety states with severe somatization and (3) anxiety states occasioned by deficits in the functioning of the organism, such as coronary disease, disfigurement or cancer. Many anxiety states can be adequately treated by the physician in general practice, using modified psychotherapeutic methods as well as such adjuvants as drugs and physiotherapy.