Chronic treatment with aripiprazole prevents development of dopamine supersensitivity and potentially supersensitivity psychosis
Open accessAbstract
BACKGROUND: Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D(2) dopamine receptors may lead to the development of supersensitivity psychosis. We investigated the chronic effects of aripiprazole (ARI) on dopamine sensitivity. METHODS: We administered ARI (1.5 mg/kg/d), haloperidol (HAL; 0.75 mg/kg/d), or vehicle (VEH) via minipump for 14 days to drug-naive rats or to rats pretreated with HAL (0.75 mg/kg/d) or VEH via minipump for 14 days. On the seventh day following treatment cessation, we examined the effects of the treatment conditions on the locomotor response to methamphetamine and on striatal D(2) receptor density (N = 4-10/condition/experiment). RESULTS: Chronic treatment with HAL led to significant increases in locomotor response and D(2) receptor density, compared with the effects of chronic treatment with either VEH or ARI; there were no significant differences in either locomotor response or D(2) density between the VEH- and ARI-treated groups. We also investigated the effects of chronic treatment with HAL, ARI, or VEH preceded by HAL or VEH treatment on locomotor response and D(2) density. ANOVA analysis indicated that the rank ordering of groups for both locomotor response and D(2) density was HAL-HAL > HAL-VEH > HAL-ARI > VEH-VEH. CONCLUSIONS: Chronic treatment with ARI prevents development of dopamine supersensitivity and potentially supersensitivity psychosis, suggesting that by reducing excessive sensitivity to dopamine and by stabilizing sensitivity for an extended period of time, ARI may be helpful for some patients with treatment-resistant schizophrenia.
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Drugs like aripiprazole that are partial agonists at the D2 receptor are less likely to induce dopaminergic hypersensitivity (as evidenced by very low rates of TD) and therefore may be less likely to cause a relapse on discontinuation, as supported by animal data, but this has not yet been examined in clinical studies.
“There is recent evidence that drugs like aripiprazole that are partial agonists at the D2 receptor are less likely to induce dopaminergic hypersensitivity (as evidenced by very low rates of TD)106 and, therefore, may be less likely to cause a relapse on discontinuation as supported by animal data,107 but this has not yet been examined in clinical studies.”
From A Method for Tapering Antipsychotic Treatment That May Minimize the Risk of Relapse (2021) · cites this paper as [107]
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- Authors
- Tadokoro, S., Okamura, N., Sekine, Y., Kanahara, N., Hashimoto, K., & Iyo, M.
- Affiliations
- Chiba University (JP)
- Center for Forensic Mental Health, Chiba University (JP)
- Corresponding author
- Tadokoro, S.
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-03-14
- Volume
- 38
- Issue
- 5
- Pages
- 1012-1020
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC3446226
- OpenAlex
- W2154296992
- Cited by
- 92
- References
- 35
- Citations by year
- 2025: 6 · 2024: 2 · 2023: 3 · 2022: 7 · 2021: 13 · 2020: 9 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 8 · 2015: 14 · 2014: 2 · 2013: 8 · 2012: 3
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Schizophrenia Bulletin (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Otsuka Pharmaceutical
- Chiba University
- Japan Society for the Promotion of Science (22390110)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- aripiprazole, dopamine supersensitivity
- MeSH terms
- Aripiprazole, Animals, Corpus Striatum, Haloperidol, Long-Term Care, Male, Methamphetamine, Motor Activity, Piperazines, Psychoses, Substance-Induced, Radioligand Assay, Schizophrenia, Antipsychotic Agents, Quinolones, Rats, Sprague-Dawley, Receptors, Dopamine D2, Dopamine Uptake Inhibitors, Rats, Dopamine D2 Receptor Antagonists
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