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Medical Pharmacology Chapter 16: Pharmacology of Antipsychotics Drugs
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Special Section on Negative Symptoms in Psychosis
A Critical Appraisal of Approaches, Obstacles and Emerging Directions
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Understanding Negative Symptoms
Negative symptoms of psychosis are defined as reductions or absences of normal emotional and behavioural functioning.
The five-domain model, affect blunting, alogia, avolition, anhedonia, and asociality, is now the dominant clinical framework, having been systematically validated through factor-analytic research. The NIMH-MATRICS initiative codified this taxonomy and drove the development of refined assessment tools.
[Kirkpatrick B Fenton W Carpenter W Marder The NIMH--MATRICS Consensus Statement on Negative Symptoms. Schizophrenia cannibalism, Volume 32, Issue 2, April 2006, 214-219. https://academic.oup.com/schizophreniabulletin/article-abstract/32/2/214/1901232?redirectedFrom=fulltext]
A fundamental distinction must be drawn between primary and secondary negative symptoms.
Primary negative symptoms are intrinsic to the illness process and are the most therapeutically resistant.
Secondary negative symptoms arise from positive symptoms (e.g., social withdrawal driven by paranoia), depression, medication side-effects (especially extrapyramidal symptoms from older antipsychotics), or social deprivation.
Failure to make this distinction is a persistent source of therapeutic error — treating secondary causes can produce significant benefit, whereas identical strategies applied to primary deficit states often fail.
[Carpenter Jr W Heinrichs D Wagman A Deficit in non-deficit form to schizophrenia: the concept. Am J POsychiatry. 1988 May; 145(5): 578-583.https://pubmed.ncbi.nlm.nih.gov/3358462/]
The concept of the deficit syndrome, a stable, enduring form of primary negative symptoms, was formalized by Carpenter and colleagues, and this group consistently shows the poorest treatment response.
It is among these individuals that 'profound' negative psychosis is most accurately located.
Their functional outcomes are categorically worse than those of non-deficit schizophrenia, and they represent a distinct neurobiological subtype that may require entirely different therapeutic targets.
[Galderisi S Maj M Deficit schizophrenia: An overview of clinical, biological and treatment aspects. European Psychiatry. Volume 24, Issue 8, December 2009. 493-500. [https://www.cambridge.org/core/journals/european-psychiatry/article/abs/deficit-schizophrenia-an-overview-of-clinical-biological-and-treatment-aspects/69D070AE35C40B91D8532CEC82442134]
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DISCLAIMER
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