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Impulse Control Disorders by Dopamine Partial Agonists: A Pharmacovigilance-Pharmacodynamic Assessment Through the FDA Adverse Event Reporting System.
Int J Neuropsychopharmacol. 2022 09 28; 25(9):727-736.IJ

Abstract

BACKGROUND

The dopaminergic partial agonism of the so-called third-generation antipsychotics (TGAs; aripiprazole, brexpiprazole, cariprazine) is hypothesized to cause impulse control disorders (ICDs). Relevant warnings by the Food and Drug Administration (FDA) were posted on aripiprazole (2016) and brexpiprazole (2018). Our study investigated the FDA Adverse Event Reporting System and the pharmacodynamic CHEMBL database to further characterize TGA-induced ICDs.

METHODS

We downloaded and pre-processed the FDA Adverse Event Reporting System up to December 2020. We adapted Bradford Hill criteria to assess each TGA's -and secondarily other antipsychotics'-causal role in inducing ICDs (pathological gambling, compulsive shopping, hyperphagia, hypersexuality), accounting for literature and disproportionality. ICD clinical features were analyzed, and their pathogenesis was investigated using receptor affinities.

RESULTS

A total of 2708 reports of TGA-related ICDs were found, primarily recording aripiprazole (2545 reports, 94%) among the drugs, and gambling (2018 reports, 75%) among the events. Bradford-Hill criteria displayed evidence for a causal role of each TGA consistent across subpopulations and when correcting for biases. Significant disproportionalities also emerged for lurasidone with compulsive shopping, hyperphagia, and hypersexuality, and olanzapine and ziprasidone with hyperphagia. Time to onset varied between days and years, and positive dechallenge was observed in 20% of cases. Frequently, co-reported events were economic (50%), obsessive-compulsive (44%), and emotional conditions (34%). 5-Hydroxytryptamine receptor type 1a agonism emerged as an additional plausible pathogenetic mechanism.

CONCLUSIONS

We detected an association between TGAs and ICDs and identified a new signal for lurasidone. ICD characteristics are behavior specific and may heavily impact on life. The role of 5-Hydroxytryptamine receptor type 1a agonism should be further explored.

Links

Authors+Show Affiliations

Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.

Rimondini Giorgini R

Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

Pharmacology Unit, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

MeSH

Antipsychotic AgentsAripiprazoleDisruptive, Impulse Control, and Conduct DisordersDopamineDopamine AgonistsHumansHyperphagiaLurasidone HydrochlorideOlanzapinePharmacovigilanceQuinolonesReceptors, SerotoninThiophenesUnited StatesUnited States Food and Drug Administration

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35639870

Citation

Fusaroli, Michele, et al. "Impulse Control Disorders By Dopamine Partial Agonists: a Pharmacovigilance-Pharmacodynamic Assessment Through the FDA Adverse Event Reporting System." The International Journal of Neuropsychopharmacology, vol. 25, no. 9, 2022, pp. 727-736.

Fusaroli M, Raschi E, Giunchi V, et al. Impulse Control Disorders by Dopamine Partial Agonists: A Pharmacovigilance-Pharmacodynamic Assessment Through the FDA Adverse Event Reporting System. Int J Neuropsychopharmacol. 2022;25(9):727-736.

Fusaroli, M., Raschi, E., Giunchi, V., Menchetti, M., Rimondini Giorgini, R., De Ponti, F., & Poluzzi, E. (2022). Impulse Control Disorders by Dopamine Partial Agonists: A Pharmacovigilance-Pharmacodynamic Assessment Through the FDA Adverse Event Reporting System. The International Journal of Neuropsychopharmacology, 25(9), 727-736. https://doi.org/10.1093/ijnp/pyac031

Fusaroli M, et al. Impulse Control Disorders By Dopamine Partial Agonists: a Pharmacovigilance-Pharmacodynamic Assessment Through the FDA Adverse Event Reporting System. Int J Neuropsychopharmacol. 2022 09 28;25(9):727-736. PubMed PMID: 35639870.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Impulse Control Disorders by Dopamine Partial Agonists: A Pharmacovigilance-Pharmacodynamic Assessment Through the FDA Adverse Event Reporting System. AU - Fusaroli,Michele, AU - Raschi,Emanuel, AU - Giunchi,Valentina, AU - Menchetti,Marco, AU - Rimondini Giorgini,Roberto, AU - De Ponti,Fabrizio, AU - Poluzzi,Elisabetta, PY - 2022/01/03/received PY - 2022/04/06/revised PY - 2022/05/24/accepted PY - 2022/6/1/pubmed PY - 2022/9/30/medline PY - 2022/5/31/entrez KW - 5-HT1A KW - Impulsive behavior KW - aripiprazole KW - brexpiprazole KW - cariprazine KW - receptor KW - serotonin SP - 727 EP - 736 JF - The international journal of neuropsychopharmacology JO - Int J Neuropsychopharmacol VL - 25 IS - 9 N2 - BACKGROUND: The dopaminergic partial agonism of the so-called third-generation antipsychotics (TGAs; aripiprazole, brexpiprazole, cariprazine) is hypothesized to cause impulse control disorders (ICDs). Relevant warnings by the Food and Drug Administration (FDA) were posted on aripiprazole (2016) and brexpiprazole (2018). Our study investigated the FDA Adverse Event Reporting System and the pharmacodynamic CHEMBL database to further characterize TGA-induced ICDs. METHODS: We downloaded and pre-processed the FDA Adverse Event Reporting System up to December 2020. We adapted Bradford Hill criteria to assess each TGA's -and secondarily other antipsychotics'-causal role in inducing ICDs (pathological gambling, compulsive shopping, hyperphagia, hypersexuality), accounting for literature and disproportionality. ICD clinical features were analyzed, and their pathogenesis was investigated using receptor affinities. RESULTS: A total of 2708 reports of TGA-related ICDs were found, primarily recording aripiprazole (2545 reports, 94%) among the drugs, and gambling (2018 reports, 75%) among the events. Bradford-Hill criteria displayed evidence for a causal role of each TGA consistent across subpopulations and when correcting for biases. Significant disproportionalities also emerged for lurasidone with compulsive shopping, hyperphagia, and hypersexuality, and olanzapine and ziprasidone with hyperphagia. Time to onset varied between days and years, and positive dechallenge was observed in 20% of cases. Frequently, co-reported events were economic (50%), obsessive-compulsive (44%), and emotional conditions (34%). 5-Hydroxytryptamine receptor type 1a agonism emerged as an additional plausible pathogenetic mechanism. CONCLUSIONS: We detected an association between TGAs and ICDs and identified a new signal for lurasidone. ICD characteristics are behavior specific and may heavily impact on life. The role of 5-Hydroxytryptamine receptor type 1a agonism should be further explored. SN - 1469-5111 UR - https://www.unboundmedicine.com/medline/citation/35639870/Impulse_Control_Disorders_by_Dopamine_Partial_Agonists:_A_Pharmacovigilance_Pharmacodynamic_Assessment_Through_the_FDA_Adverse_Event_Reporting_System_ DB - PRIME DP - Unbound Medicine ER -