A Comprehensive Review of Schizophrenia and Antipsychotic Metabolism as a Predictor of Treatment Response

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Abstract

Some patients with schizophrenia fail to respond to standard antipsychotics and are considered treatment-resistant. In these cases, clozapine is the only antipsychotic with proven efficacy, but its use is complicated by severe adverse effects, complex monitoring requirements, and non-response.

Variation within the CYP450 enzymes CYP1A2, CYP2D6, CYP3A4, and CYP2C19 has been linked to the differential metabolism of antipsychotics. Testing for CYP450 single nucleotide polymorphisms may be a useful predictor of treatment resistance and could inform pharmacogenetic recommendations to identify potential treatment non-responders. Nonetheless, it remains uncertain whether differential antipsychotic metabolism is directly related to treatment efficacy.

This comprehensive narrative review endeavours to delve into the molecular and genetic basis of schizophrenia, and discuss the current treatments available. In particular, we aim to examine the aetiology of treatment resistance in schizophrenia through available literature and discuss current challenges within the field.

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Most cited references 76

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Schizophrenia: a concise overview of incidence, prevalence, and mortality.

J. McGrath, S. Saha, D. CHANT … (2008)

Recent systematic reviews have encouraged the psychiatric research community to reevaluate the contours of schizophrenia epidemiology. This paper provides a concise overview of three related systematic reviews on the incidence, prevalence, and mortality associated with schizophrenia. The reviews shared key methodological features regarding search strategies, analysis of the distribution of the frequency estimates, and exploration of the influence of key variables (sex, migrant status, urbanicity, secular trend, economic status, and latitude). Contrary to previous interpretations, the incidence of schizophrenia shows prominent variation between sites. The median incidence of schizophrenia was 15.2/100,000 persons, and the central 80% of estimates varied over a fivefold range (7.7-43.0/100,000). The rate ratio for males:females was 1.4:1. Prevalence estimates also show prominent variation. The median lifetime morbid risk for schizophrenia was 7.2/1,000 persons. On the basis of the standardized mortality ratio, people with schizophrenia have a two- to threefold increased risk of dying (median standardized mortality ratio = 2.6 for all-cause mortality), and this differential gap in mortality has increased over recent decades. Compared with native-born individuals, migrants have an increased incidence and prevalence of schizophrenia. Exposures related to urbanicity, economic status, and latitude are also associated with various frequency measures. In conclusion, the epidemiology of schizophrenia is characterized by prominent variability and gradients that can help guide future research.

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Rethinking schizophrenia.

Thomas Insel (2010)

How will we view schizophrenia in 2030? Schizophrenia today is a chronic, frequently disabling mental disorder that affects about one per cent of the world's population. After a century of studying schizophrenia, the cause of the disorder remains unknown. Treatments, especially pharmacological treatments, have been in wide use for nearly half a century, yet there is little evidence that these treatments have substantially improved outcomes for most people with schizophrenia. These current unsatisfactory outcomes may change as we approach schizophrenia as a neurodevelopmental disorder with psychosis as a late, potentially preventable stage of the illness. This 'rethinking' of schizophrenia as a neurodevelopmental disorder, which is profoundly different from the way we have seen this illness for the past century, yields new hope for prevention and cure over the next two decades.

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Schizophrenia

Michael J Owen, Akira Sawa, Preben B Mortensen (2016)

Summary Schizophrenia is a complex, heterogeneous behavioural and cognitive syndrome whose origins appear to lie in genetic and/or environmental disruption of brain development. Dysfunction of dopaminergic neurotransmission appears to contribute to the genesis of psychotic symptoms but the evidence also points to a more widespread and variable involvement of brain areas and circuits. There is emerging evidence that disturbances of synaptic function might underlie abnormalities of neuronal connectivity possibly involving interneurons, but the precise nature, location and timing of these events is uncertain. Current treatment consists largely in the administration of antipsychotic drugs combined with psychological therapies, social support and rehabilitation, but there is a pressing need for more effective treatments and for services to be delivered more effectively. Progress in understanding the disorder has been great in recent years with advances in genomics, epidemiology and neuroscience, and the opportunities for further scientific advance are great: but so are the challenges.

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Author and article information

Journal

Journal ID (nlm-ta): Cureus

Journal ID (iso-abbrev): Cureus

Journal ID (issn): 2168-8184

Title: Cureus

Publisher: Cureus (Palo Alto (CA) )

ISSN (Electronic): 2168-8184

Publication date (Electronic, pub): 24 July 2024

Publication date (Electronic, collection): July 2024

Volume: 16

Issue: 7

Electronic Location Identifier: e65279

Affiliations

[1 ] General Internal Medicine, St. George's Hospital, London, GBR

[2 ] General Surgery, Medway NHS Foundation Trust, London, GBR

Author notes

Mia Pham mhinespham@ 123456gmail.com

Article

DOI: 10.7759/cureus.65279

PMC ID: 11343069

SO-VID: 517ac609-1be6-4b96-9846-a96029fac220

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This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Date accepted : 24 July 2024

A Comprehensive Review of Schizophrenia and Antipsychotic Metabolism as a Predictor of Treatment Response

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Most cited references 76

Schizophrenia: a concise overview of incidence, prevalence, and mortality.

Rethinking schizophrenia.

Schizophrenia

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