Antipsychotic polypharmacy and high-dose antipsychotic therapy compared to antipsychotic monotherapy at standard doses in schizophrenia – a systematic review
Antipsychotic polypharmacy and high-dose antipsychotic therapy compared to antipsychotic monotherapy at standard doses in schizophrenia – a systematic review
Background: schizophrenia is considered to have a lifetime prevalence of around 1%. Up to 30% of patients diagnosed with schizophrenia are subsequently categorised as treatment resistant. Current guidelines advise against the use of antipsychotic polypharmacy (APP) or high-dose antipsychotic therapy (HDAT) in the treatment of schizophrenia; however, these treatment approaches continue to be used in up to 25% of cases.
Aims: tis review was to evaluate the evidence for the efficacy and tolerability of APP and HDAT as an alternative to antipsychotic monotherapy at standard doses in the treatment of schizophrenia.
Methods: this is a systematic review. We searched PubMed, EMBASE and PsycINFO, for eligible trials published prior to 24 March 2023. The protocol was registered on PROSPERO (CRD42023408785). Quality assessment was conducted using the Revised Cochrane risk-of-bias tool for randomised trials.Results:A total of 14 studies were included in this review. Two studies demonstrated clinically significant improvement with APP compared to standard treatment. There was no clear evidence that APP or HDAT is definitively less tolerable than antipsychotic monotherapy at a standard dose.
Conclusions: this review found limited evidence for the efficacy of APP and HDAT in the treatment of schizophrenia over the use of antipsychotic monotherapy at a standard dose. The relative tolerability was unclear. Management of treatment-resistant schizophrenia remains a prominent clinical issue and further research, including high-quality large-scale Randomised Controlled Trials (RCTs) of APP and HDAT in patients who have been unresponsive to clozapine, would be of significant benefit to the field of psychiatry.
Schizophrenia, antipsychotic polypharmacy, dopamine receptor antagonists, dopamine receptor partial agonists, drugs for psychosis, high-dose antipsychotic therapy, treatment-resistant schizophrenia
132-140
Lawrence, Christopher
9f61058b-220f-4bfa-a9fb-b33a7af1dda2
Roberts, Chloe
47deddc5-d3bc-4113-b3e2-9d255620e76b
Galides, Chloe
b2856b4a-2fb0-4b29-9c9a-0fa6040d6261
Chamberlain, Sam
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Hou, Ruihua
470bdcbc-93a9-4dad-aac5-26d455c34376
1 February 2025
Lawrence, Christopher
9f61058b-220f-4bfa-a9fb-b33a7af1dda2
Roberts, Chloe
47deddc5-d3bc-4113-b3e2-9d255620e76b
Galides, Chloe
b2856b4a-2fb0-4b29-9c9a-0fa6040d6261
Chamberlain, Sam
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Hou, Ruihua
470bdcbc-93a9-4dad-aac5-26d455c34376
Lawrence, Christopher, Roberts, Chloe, Galides, Chloe, Chamberlain, Sam and Hou, Ruihua
(2025)
Antipsychotic polypharmacy and high-dose antipsychotic therapy compared to antipsychotic monotherapy at standard doses in schizophrenia – a systematic review.
Journal of Psychopharmacology, 39 (2), .
(doi:10.1177/02698811241303652).
Abstract
Background: schizophrenia is considered to have a lifetime prevalence of around 1%. Up to 30% of patients diagnosed with schizophrenia are subsequently categorised as treatment resistant. Current guidelines advise against the use of antipsychotic polypharmacy (APP) or high-dose antipsychotic therapy (HDAT) in the treatment of schizophrenia; however, these treatment approaches continue to be used in up to 25% of cases.
Aims: tis review was to evaluate the evidence for the efficacy and tolerability of APP and HDAT as an alternative to antipsychotic monotherapy at standard doses in the treatment of schizophrenia.
Methods: this is a systematic review. We searched PubMed, EMBASE and PsycINFO, for eligible trials published prior to 24 March 2023. The protocol was registered on PROSPERO (CRD42023408785). Quality assessment was conducted using the Revised Cochrane risk-of-bias tool for randomised trials.Results:A total of 14 studies were included in this review. Two studies demonstrated clinically significant improvement with APP compared to standard treatment. There was no clear evidence that APP or HDAT is definitively less tolerable than antipsychotic monotherapy at a standard dose.
Conclusions: this review found limited evidence for the efficacy of APP and HDAT in the treatment of schizophrenia over the use of antipsychotic monotherapy at a standard dose. The relative tolerability was unclear. Management of treatment-resistant schizophrenia remains a prominent clinical issue and further research, including high-quality large-scale Randomised Controlled Trials (RCTs) of APP and HDAT in patients who have been unresponsive to clozapine, would be of significant benefit to the field of psychiatry.
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lawrence-et-al-2024-antipsychotic-polypharmacy-and-high-dose-antipsychotic-therapy-compared-to-antipsychotic
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e-pub ahead of print date: 10 December 2024
Published date: 1 February 2025
Keywords:
Schizophrenia, antipsychotic polypharmacy, dopamine receptor antagonists, dopamine receptor partial agonists, drugs for psychosis, high-dose antipsychotic therapy, treatment-resistant schizophrenia
Identifiers
Local EPrints ID: 502537
URI: http://eprints.soton.ac.uk/id/eprint/502537
ISSN: 0269-8811
PURE UUID: 8507be3f-c70b-42f4-857b-72683dfa09a7
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Date deposited: 30 Jun 2025 17:44
Last modified: 11 Sep 2025 03:16
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Contributors
Author:
Christopher Lawrence
Author:
Chloe Roberts
Author:
Chloe Galides
Author:
Sam Chamberlain
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