Biological Predictors of Clozapine Response: A Systematic Review
Background: Clozapine is the recommended antipsychotic for treatment-resistant schizophrenia (TRS) but there is significant variability between patients in the degree to which clozapine will improve symptoms. The biological basis of this variability is unknown. Although clozapine has efficacy in TRS...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-07-01
|
| Series: | Frontiers in Psychiatry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fpsyt.2018.00327/full |
| _version_ | 1818197859822993408 |
|---|---|
| author | Ruta Samanaite Amy Gillespie Amy Gillespie Kyra-Verena Sendt Grant McQueen James H. MacCabe Alice Egerton |
| author_facet | Ruta Samanaite Amy Gillespie Amy Gillespie Kyra-Verena Sendt Grant McQueen James H. MacCabe Alice Egerton |
| author_sort | Ruta Samanaite |
| collection | DOAJ |
| description | Background: Clozapine is the recommended antipsychotic for treatment-resistant schizophrenia (TRS) but there is significant variability between patients in the degree to which clozapine will improve symptoms. The biological basis of this variability is unknown. Although clozapine has efficacy in TRS, it can elicit adverse effects and initiation is often delayed. Identification of predictive biomarkers of clozapine response may aid initiation of clozapine treatment, as well as understanding of its mechanism of action. In this article we systematically review prospective or genetic studies of biological predictors of response to clozapine.Methods: We searched the PubMed database until 20th January 2018 for studies investigating “clozapine” AND (“response” OR “outcome”) AND “schizophrenia.” Inclusion required that studies examined a biological variable in relation to symptomatic response to clozapine. For all studies except genetic-studies, inclusion required that biological variables were measured before clozapine initiation.Results: Ninety-eight studies met the eligibility criteria and were included in the review, including neuroimaging, blood-based, cerebrospinal fluid (CSF)-based, and genetic predictors. The majority (70) are genetic studies, collectively investigating 379 different gene variants, however only three genetic variants (DRD3 Ser9Gly, HTR2A His452Tyr, and C825T GNB3) have independently replicated significant findings. Of the non-genetic variables, the most consistent predictors of a good response to clozapine are higher prefrontal cortical structural integrity and activity, and a lower ratio of the dopamine and serotonin metabolites, homovanillic acid (HVA): 5-hydroxyindoleacetic acid (5-HIAA) in CSF.Conclusions: Recommendations include that future studies should ensure adequate clozapine trial length and clozapine plasma concentrations, and may include multivariate models to increase predictive accuracy. |
| first_indexed | 2024-12-12T01:56:41Z |
| format | Article |
| id | doaj.art-618bfc37ff6d4c8f9bc7d86d0b43aab4 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-12T01:56:41Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-618bfc37ff6d4c8f9bc7d86d0b43aab42022-12-22T00:42:20ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402018-07-01910.3389/fpsyt.2018.00327377267Biological Predictors of Clozapine Response: A Systematic ReviewRuta Samanaite0Amy Gillespie1Amy Gillespie2Kyra-Verena Sendt3Grant McQueen4James H. MacCabe5Alice Egerton6Psychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United KingdomPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United KingdomDepartment of Psychiatry, University of Oxford, Oxford, United KingdomPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United KingdomPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United KingdomPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United KingdomPsychosis Studies Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United KingdomBackground: Clozapine is the recommended antipsychotic for treatment-resistant schizophrenia (TRS) but there is significant variability between patients in the degree to which clozapine will improve symptoms. The biological basis of this variability is unknown. Although clozapine has efficacy in TRS, it can elicit adverse effects and initiation is often delayed. Identification of predictive biomarkers of clozapine response may aid initiation of clozapine treatment, as well as understanding of its mechanism of action. In this article we systematically review prospective or genetic studies of biological predictors of response to clozapine.Methods: We searched the PubMed database until 20th January 2018 for studies investigating “clozapine” AND (“response” OR “outcome”) AND “schizophrenia.” Inclusion required that studies examined a biological variable in relation to symptomatic response to clozapine. For all studies except genetic-studies, inclusion required that biological variables were measured before clozapine initiation.Results: Ninety-eight studies met the eligibility criteria and were included in the review, including neuroimaging, blood-based, cerebrospinal fluid (CSF)-based, and genetic predictors. The majority (70) are genetic studies, collectively investigating 379 different gene variants, however only three genetic variants (DRD3 Ser9Gly, HTR2A His452Tyr, and C825T GNB3) have independently replicated significant findings. Of the non-genetic variables, the most consistent predictors of a good response to clozapine are higher prefrontal cortical structural integrity and activity, and a lower ratio of the dopamine and serotonin metabolites, homovanillic acid (HVA): 5-hydroxyindoleacetic acid (5-HIAA) in CSF.Conclusions: Recommendations include that future studies should ensure adequate clozapine trial length and clozapine plasma concentrations, and may include multivariate models to increase predictive accuracy.https://www.frontiersin.org/article/10.3389/fpsyt.2018.00327/fullclozapinetreatment responseschizophreniatreatment-resistanceresponse biomarker |
| spellingShingle | Ruta Samanaite Amy Gillespie Amy Gillespie Kyra-Verena Sendt Grant McQueen James H. MacCabe Alice Egerton Biological Predictors of Clozapine Response: A Systematic Review Frontiers in Psychiatry clozapine treatment response schizophrenia treatment-resistance response biomarker |
| title | Biological Predictors of Clozapine Response: A Systematic Review |
| title_full | Biological Predictors of Clozapine Response: A Systematic Review |
| title_fullStr | Biological Predictors of Clozapine Response: A Systematic Review |
| title_full_unstemmed | Biological Predictors of Clozapine Response: A Systematic Review |
| title_short | Biological Predictors of Clozapine Response: A Systematic Review |
| title_sort | biological predictors of clozapine response a systematic review |
| topic | clozapine treatment response schizophrenia treatment-resistance response biomarker |
| url | https://www.frontiersin.org/article/10.3389/fpsyt.2018.00327/full |
| work_keys_str_mv | AT rutasamanaite biologicalpredictorsofclozapineresponseasystematicreview AT amygillespie biologicalpredictorsofclozapineresponseasystematicreview AT amygillespie biologicalpredictorsofclozapineresponseasystematicreview AT kyraverenasendt biologicalpredictorsofclozapineresponseasystematicreview AT grantmcqueen biologicalpredictorsofclozapineresponseasystematicreview AT jameshmaccabe biologicalpredictorsofclozapineresponseasystematicreview AT aliceegerton biologicalpredictorsofclozapineresponseasystematicreview |