Challenging the Need for Sustained Blockade of Dopamine D2 Receptor Estimated From Antipsychotic Plasma Levels in the Maintenance Treatment of Schizophrenia: A Single-Blind, Randomized, Controlled Study
Abstract
Objective Blockade of dopamine D₂ receptors with antipsychotics above 65% is associated with optimal chance of clinical response although recent data suggest a lower threshold for the maintenance treatment of schizophrenia. The objective of this study was to prospectively examine whether such continuous high blockade would be necessary for maintenance treatment. Method In this single-blind, 52-week, randomized controlled trial, clinically stable patients with schizophrenia receiving risperidone or olanzapine were randomly assigned to the continuous D₂ blockade (i.e. an estimated trough D2 blockade of >65%) or non-continuous blockade group (i.e. an estimated peak level of >65% with an estimated trough level of Results Sixty-eight subjects (34 in each group) were enrolled. Twenty-six (76.5%) and thirty-one (91.2%) subjects completed the study in the continuous and non-continuous blockade groups, respectively, without any significant group difference. No significant differences were found on any of the assessment scales between the two groups. The degree of dosage change was small in both groups. Conclusion These results offer support that the threshold for D₂ receptor blockade in the maintenance treatment can be lower than 65%. However, these preliminary findings have to be confirmed through double-blind, larger scale trials with longer follow-up periods.
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In four RCTs determining the effect of dose reduction, a paradoxical weight increase was seen in the reduced group.
“In four RCTs determining the effect of dose reduction, a paradoxical weight increase was seen in the reduced group (47, 56, 73, 96)”
From Reversibility of Antipsychotic-Induced Weight Gain: A Systematic Review and Meta-Analysis (2021) · cites this paper as [47]
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Uchida, H., Takeuchi, H., Graff-Guerrero, A., Suzuki, T., Watanabe, K., & Mamo, D. C. (2011) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0b013e318218d339 · Cited by 94 · see citing works
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Antipsychotic-Induced Dopamine Supersensitivity Psychosis: Pharmacology, Criteria, and Therapy
Chouinard, G., Samaha, A.-N., Chouinard, V.-A., Peretti, C.-S., Kanahara, N., Takase, M., & Iyo, M. (2017) · Psychotherapy and Psychosomatics · doi:10.1159/000477313 · Cited by 270 · see citing works
Reversibility of Antipsychotic-Induced Weight Gain: A Systematic Review and Meta-Analysis
Speyer, H., Westergaard, C., Albert, N., Karlsen, M., Stürup, A. E., Nordentoft, M., & Krogh, J. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.577919 · Cited by 44 · see citing works
Liu, C.-C., & Takeuchi, H. (2020) · CNS Drugs · doi:10.1007/s40263-019-00682-8 · Cited by 19 · see citing works
- Authors
- Tsuboi, T., Suzuki, T., Bies, R. R., Remington, G., Pollock, B. G., Mimura, M., & Uchida, H.
- Affiliations
- Keio University (JP)
- Centre for Addiction and Mental Health (CA)
- Corresponding author
- Uchida, Hiroyuki
- ORCID
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 164
- Issue
- 1-3
- Pages
- 149-154
- ISSN
- 0920-9964 (ISSN-L)
- OpenAlex
- W1977894652
- Cited by
- 13
- References
- 1
- Citations by year
- 2023: 2 · 2021: 4 · 2020: 1 · 2019: 3 · 2017: 2 · 2016: 1
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
- Keywords
- dopamine D2 receptor blockade
- MeSH terms
- Adult, Aged, Female, Follow-Up Studies, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Schizophrenia, Antipsychotic Agents, Single-Blind Method, Treatment Outcome, Dopamine D2 Receptor Antagonists
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