Die Behandlung endogener Depressionen mit Psychopharmaka

Kielholz, P; Pöldinger, W

doi:10.1055/s-0028-1105133

Cited by 37 publications

(7 citation statements)

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“…It appears that reductions in anxiety and hostility are the initial signs of response in depressed patients to the tricyclic drugs, preceding the reduction of depressed mood (Haskell et al 1975;Katz et al 1987Katz et al , 1991. Such evidence supports the results of earlier research by Kielholz and Poldinger (1968) and Carlsson et al (1969), indicating that the tricycle drugs have multiple actions, i.e. both tranquilizing and mood-elevating effects.…”

Section: Conceptions Of Depression and The Mechanisms Of Drug Actionsupporting

confidence: 81%

Enhancing the Technology of Clinical Trials and the Trials Model to Evaluate Newly Developed, Targeted Antidepressants

Katz

Halbreich

Bowden

et al. 2002

Neuropsychopharmacology

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Concern about disappointing results from recent multicenter trials of new antidepressants prompted several ACNP workshops on "improving the technology of clinical trials." The workshops focused on technical problems, such as patient screening, reliability of clinical ratings, and the role of the placebo control. They aimed to determine how to 27 , NO . 3 ducing adverse events, and lessening the complexity of dosing regimens. In addition, attention is currently focused on accelerating the onset of drug action to generate more rapidly acting antidepressants. Unfortunately, recently conducted multi-center clinical trials of some of these agents encountered serious technical problems and did not produce the results anticipated from preclinical studies. Although this may be partly due to limitations in extrapolating pre-clinical data to patients, it may also be that there are significant constraints in the current clinical trials model that make it difficult to demonstrate efficacy.The current clinical trials model is now 30 years old. The essential principles of randomization, double blind evaluation, and a placebo control remain sound. But other important aspects of the research design and the methodology are no longer sufficient or well suited to the testing of these new drugs. In effect, such deficiencies in current trial methodologies make it increasingly difficult to demonstrate antidepressant efficacy of these new drugs.One important reason the current model has proved inadequate is that it was initially applied to hospitalized depressed patients. Today new drugs are tested almost exclusively on outpatient samples, many of whom are symptomatic volunteers, responding to advertisements. Depressed outpatients have milder depressive symptomatology than the predominantly inpatient samples used to test the first established drugs. Patients with milder severity provide a narrower range of possible change, and produce a greater number of placebo responders (Fisher et al. 1965;Bowden et al. 2000;Khan et al. 2002).As a consequence of the smaller difference between active treatment and placebo treatment, larger patient samples and/or more sensitive clinical methods are needed to detect differences between drug and placebo. The most commonly utilized scales, the Hamilton Depression Rating Scale (HDRS) (Hamilton 1960) and the Clinical Global Impression Scale (CGI) (Guy 1976), were designed to measure changes in overall severity of the disorder. These scales are not sufficiently sensitive to assess the specific behavioral changes brought about by the newer drugs (Montgomery and Asberg 1979). Further, intensive evaluation of symptomatology and behavioral change are carried out infrequently with outpatients, making evaluation of rapidity of response problematic. Consequently, it appears important to improve the technology applied to assessing the specific actions, onset, and efficacy of the newer drugs.Acknowledging the increased complexity of the goals of clinical trials and the need to improve trial procedures, the desi...

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Section: Conceptions Of Depression and The Mechanisms Of Drug Actionsupporting

confidence: 81%

Enhancing the Technology of Clinical Trials and the Trials Model to Evaluate Newly Developed, Targeted Antidepressants

Katz

Halbreich

Bowden

et al. 2002

Neuropsychopharmacology

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“…Overcoming them involves a shift in approach or perspective from the model used to study the efficacy of a drug for a specific mental disorder. They require taking into account information concerning: (1) the clinical phenomena of the disorder of depression; namely, that depression is not unitary, but multifaceted (Klerman, 1972), comprised of several significant emotional, cognitive, and behavioral components; and that (2) the tricyclic and the newer antidepressant drugs have multiple behavioral effects on the disorder (Kielholz and Poldinger, 1968) which derive from multiple actions on the functioning of central neurotransmitter systems (e.g., Carlsson et al, 1969).…”

Section: Methodologic and Conceptual Obstacles To Measuring Multiple mentioning

confidence: 99%

Onset of antidepressant activity: Reexamining the structure of depression and multiple actions of drugs

1996

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The question of when antidepressant drugs (AD) initiate significant clinical actions in depressed patients is still unsettled. Findings from early studies on whether there is a lag in the onset of therapeutic actions were in disagreement. More recent results with the selective serotonin reuptake inhibitors (SSRIs) and other new Ads indicate that clinical actions occur within the first 2 weeks. In this paper, evidence from efficacy studies with the Ads is reviewed and the methodologic and conceptual obstacles to achieving definitive results about the onset issue are analyzed. Depression, formerly viewed as a homogenous disorder, is now seen as heterogenous and multifaceted in structure. Such major structural components as anxiety and disturbed psychomotor functioning can be as significant to the core of the disorder as depressed mood itself. Further, the Ads have been shown to act initially on different facets of the clinical disorder which then result in multiple clinical actions, e.g., an initial reduction in anxiety followed by stimulation of motor activity. Data from the NIMH Collaborative Study of the Psychobiology of Depression are used to illustrate: (1) the componential structure of severe depressive disorder; (2) the sequence of change in the major behavioral components of the disorder associated with the tricyclic drugs; (3) the consequent ‘multiple’ onsets of clinical actions; and (4) measurement of the clinical significance and visibility of the early behavioral changes. Recent results describing new behavioral and methodological approaches, the use of early clinical changes to predict outcome, and strategies for designing sound studies of onset are discussed. Depression and Anxiety 4:257–267, 1996/1997.© 1997 Wiley‐Liss, Inc.

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“…Effects of antidepressants at histamine receptors may or may not fit with the role of reserpine induced depression and its blockade by antidepressants. Reserpine lowers brain histamine levels (20) and releases histamine The qualitative data in columns 2 and 3 were derived from reviews of c1inical and animal studies (1, 3,7,9,12,191. In animals, sedation and psychomotor activation were measured in terms of alteration of barbiturateinduced sleep, cortical electroencephalagram, spontaneous motor activity, and drowsiness; hypotensive potential was demonstrated as decreases in blood pressure and heart rate after systemic administration, and as blocking ability in isolated aortic and papillary muscle preparations.…”

Section: Antidepressant Drugs and Histamine H Receptorsmentioning

confidence: 99%

Tricyclic Antidepressant Drug Interactions with Histamine and α-Adrenergic Receptors

Snyder¹

1980

Pharmacopsychiatry

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Tricyclic antidepressant drugs are remarkable in their therapeutic actions. When given acutely they are generally sedating. Then after a lag of 1-3 weeks, they alleviate depressive symptoms. Besides the delayed psychic energizing properties, the immediate apparent sedative actions may have importance for the relief of psychomotor agitation. This article describes influences of the drugs on histamine H1 and alpha-adrenergic receptors which may be of relevance to the energizing effects and relief of psychomotor agitation.

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Die Behandlung endogener Depressionen mit Psychopharmaka

Cited by 37 publications

References 0 publications

Enhancing the Technology of Clinical Trials and the Trials Model to Evaluate Newly Developed, Targeted Antidepressants

Enhancing the Technology of Clinical Trials and the Trials Model to Evaluate Newly Developed, Targeted Antidepressants

Onset of antidepressant activity: Reexamining the structure of depression and multiple actions of drugs

Tricyclic Antidepressant Drug Interactions with Histamine and α-Adrenergic Receptors

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