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Shorter, E. & Tyrer, P. Separation of anxiety and depressive disorders: blind alley in psychopharmacology and classification of disease. BMJ 327, 158-160

History of Medicine Program, Faculty of Medicine, University of Toronto, Toronto ON, Canada M5G 1VJ.
BMJ (online) (Impact Factor: 16.38). 08/2003; 327(7407):158-60. DOI: 10.1136/bmj.327.7407.158
Source: PubMed

ABSTRACT ne current division between anxiety and depression is increasingly recognised as inadequate. In the community, most mood disorders present as a combination of depression and anxiety. Yet the Food and Drug Administration in the United States, which has become the world bellwether of drug approval, indicates drugs either for major depression or for the various forms of anxiety recognised by the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM). As a result, the pharmaceutical industry is compelled to develop drugs for diagnoses that are of questionable clinical relevance. This is one reason for the big slowdown in drug discovery in psychiatric drugs. A return to the former unitary classification of mood and anxiety disorders as nervousness or cothymia might represent a way out of this blind alley.

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Available from: Edward Shorter, Oct 17, 2014
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    • "Heterogeneity in depression leads to decreased clinical specificity and a loss of statistical power. Dichotomizing results in the dismissal of valuable information, which may lead to biased results (Shorter and Tyrer, 2003). A dimensional model of psychopathology resolves both issues by assuming that symptom severity follows a continuum rather than a dichotomy. "
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    ABSTRACT: We examined the association of cognitive vulnerability to depression with changes in homogeneous measures of depressive symptoms. Baseline and 1-year follow-up data were obtained from 2981 participants of the Netherlands study of depression and anxiety. Multivariate regression analyses were carried out on cognitive reactivity, locus of control and implicit and explicit self-depressive associations in combination with negative life events. The purpose of this analysis was to predict changes on the mood/cognition and anxiety/arousal subscales of the inventory of depressive symptomatology - self report. Cognitive reactivity, locus of control and explicit self-depressive associations were independently associated with changes in depressive symptoms after adjustment for covariates and baseline severity (all p<0.01). Negative life-events interacted with cognitive vulnerability to depression to predict depressive symptoms. Locus of control (b1=0.16, SE=0.02, η(2)=0.01; b2=0.10, SE=0.02, η(2)=0.004, F=8.69, p<0.01) and explicit self-depressive associations (b1=0.10, SE=0.03, η(2)=0.02; b2=0.02, SE=0.04, F=7.50, p<0.01) were more strongly associated with the cognitive (b1) than the somatic (b2) symptom dimension of depression. The study sample is over-inclusive of depressed patients. Therefore it might be problematic generalizing the findings to the general population. Cognitive etiological factors may play a role in a "cognitive" subtype of depression. The findings strengthen the notion that homogeneous measures of depressive symptoms enable a greater degree of discrimination between subtypes than a multidimensional conception of depression.
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    • "This has led to much criticism of the models used. Likewise, there has been a growing discussion focused on whether anxiety and depression should be isolated from a drug development perspective (Shorter and Tyrer, 2003). Moreover, given the relative success of SSRIs, it is becoming clear that many pharmaceutical companies are compelled to develop a 'one pill fits all' approach to anxiety and mood disorders. "
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    • "Although the hypothesis elaborated in the present article suggests a molecular mechanism for psychological pain and physical pain in depression, it does not propose a molecular mechanism for other symptoms or common comorbidities of depression, such as anxiety (Shorter and Tyrer 2003), irritability (Snaith and Taylor 1985), guilt (American Psychiatric Association 2000), and worthlessness (American Psychiatric Association 2000), nor does it provide a mechanism by which inflammatory mediators in the brain induce the sickness symptoms that are common in depression, such as sleep and appetite disturbances (American Psychiatric Association 2000), fatigue (American Psychiatric Association 2000), nausea (Haug et al. 2002), diarrhea (Sugahara et al. 2004), or fever (Sugahara et al. 2004). In a separate manuscript in preparation (Wager-Smith 2010) we present a theoretical model whereby these symptoms respresent a family of behavioral defenses that are controlled by neuronal circuits for which the trigger threshold can be altered by inflammatory mediators. "
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