Selective serotonin reuptake inhibitors and manic switch: A pharmacovigilance and pharmacodynamical study

Çıray, Remzi Oğulcan; Halac, Eren; Turan, Serkan; Tunçtürk, Mustafa; Özbek, Mutlu Muhammed; Ermiş, Çağatay

doi:10.1016/j.ajp.2021.102891

Cited by 4 publications

(4 citation statements)

References 42 publications

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“…Among this richness of molecular targets, there is plausibly the key to better management of drug‐related ICDs. Integrating pharmacovigilance and pharmacodynamic data may help in the search for the pathogenetic mechanisms of drug‐induced conditions 26–40 . Therefore, we aim to generate novel hypotheses on the underlying mechanistic basis of drug‐induced ICDs.…”

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confidence: 99%

“…Integrating pharmacovigilance and pharmacodynamic data may help in the search for the pathogenetic mechanisms of drug-induced conditions. [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] Therefore, we aim to generate novel hypotheses on the underlying mechanistic basis of drug-induced ICDs. A more comprehensive understanding of the role of other molecular targets would drive a more successful drug switching in case of ICDs onset and may support the development and repurposing of pharmacological treatments for ICDs.…”

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confidence: 99%

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Exploring the underlying mechanisms of drug‐induced impulse control disorders: a pharmacovigilance‐pharmacodynamic study

Fusaroli

Giunchi

Battini

et al. 2022

Psychiatry Clin Neurosci

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Introduction: Impulse control disorders (e.g. pathological gambling, hypersexuality) may develop as adverse reactions to drugs. Pathogenetic hypotheses have mainly focused on D3-receptor agonism, and switching to alternatives with different pharmacologic mechanisms represents a common management strategy. Nonetheless, treatment failure is common and gaining pathophysiological insights is needed.Aim: We aimed to identify targets potentially contributing to pathologic impulsivity.Method: We performed a pharmacovigilance-pharmacodynamic study on dopamine agonists and antipsychotics using the Food and Drug Administration Adverse Event Reporting System (January 2004-December 2021). We estimated disproportionate reporting using the Bayesian information component. Using online public databases (IUPHAR, ChEMBL, PDSP, DrugBank), we calculated drug occupancies. To identify the targets potentially contributing to impulsivity, we fitted univariate regression models interpolating information components and occupancies within dopamine agonists and antipsychotics. Sensitivity analyses were performed to check for the robustness of the results.Results: Among 19 887 reports of impulsivity, 5898 recorded an antipsychotic, and 3100 a dopamine agonist. The more robust signals concerned aripiprazole (N = 3091; median information component [95% confidence interval] = 4. 51[4.45-4.55]) and brexpiprazole (229; 4.00[3.78-4.16]) for antipsychotics, pergolide (105; 5.82[5.50-6.06]) and pramipexole (2009; 5.43[5.36-5.48]) for dopamine agonists. Robust, significant positive associations between drug occupancy and impulsivity reporting were found for D3 within dopamine agonists (beta = 1.52; P-value = 0.047) and 5-HT1a within antipsychotics (1.92, 0.029). Conclusion:Our results supported the role of D3-receptor agonism in inducing impulsivity in dopamine receptor agonists and identified a potential role of 5-HT1a receptor agonism in antipsychotics. Investigating these receptors may drive towards a better management of drug-induced impulsivity.

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confidence: 99%

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confidence: 99%

Exploring the underlying mechanisms of drug‐induced impulse control disorders: a pharmacovigilance‐pharmacodynamic study

Fusaroli

Giunchi

Battini

et al. 2022

Psychiatry Clin Neurosci

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“…PV-PD studies represent an innovative approach to establishing a correlation between the binding affinities of drugs for their pharmacological targets and the associated reporting risks for AEs observed within an extensive pharmacovigilance database ( Nguyen et al, 2017 ). To illustrate, this approach has recently been employed to explore the etiology of AEs like antidepressant-induced hyponatremia ( Mazhar et al, 2019 ), manic switch ( Çiray et al, 2021 ), antipsychotics-related pneumonia ( Cepaityte et al, 2021 ), obsessive-compulsive disorder ( Burk et al, 2023 ), and impulse control disorders ( Fusaroli et al, 2022 ). Our findings could contribute greatly to the understanding of antipsychotic medications and SD-related side effects and help develop safer and more effective treatments for patients.…”

Section: Discussionmentioning

confidence: 99%

The atypical antipsychotics and sexual dysfunction: a pharmacovigilance-pharmacodynamic study

Cheng,

Chen,

Zhao

et al. 2024

Front. Pharmacol.

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BackgroundAtypical antipsychotics (AAPs)-induced sexual dysfunction (SD) is a frequent issue in clinical practice, often underestimated by clinicians and not extensively researched. The current study aimed to quantify the strength of association between the use of different AAPs and SD using real-world data from the FDA Adverse Event Reporting System (FAERS), as well as investigate the receptor mechanisms that are involved.MethodsData from the FAERS database from the first quarter of 2004 to the third quarter of 2023 were queried through OpenVigil 2.1. Disproportionality analysis was estimated using the reporting odds ratio (ROR) and information component (IC) methods, and linear regression was used to investigate the relationship between ROR and receptor occupancy which was estimated using in vitro receptor binding profiles.ResultsOur analysis yielded 4839 reports that co-mentioned AAP and SD events, and the findings revealed statistical associations between 12 AAPs and SD. The highest signal value was identified for iloperidone reporting retrograde ejaculation with iloperidone (ROR = 832.09, ROR025 = 552.77; IC = 9.58, IC025 = 6.36), followed by compulsive sexual behavior with aripiprazole (ROR = 533.02, ROR025 = 435.90; IC = 7.30, IC025 = 5.97), and psychosexual disorder for aripiprazole (ROR = 145.80, ROR025 = 109.57; IC025 = 6.47, IC025 = 4.86). Different characteristics of the SD side effects in each AAPs were discovered after further data mining. Regression analysis revealed potential effects for receptor occupancy of D2, D3, and 5-HT1A receptors on ROR. However, no significant correlation persisted following sensitivity analyses.ConclusionThis is the first study to investigate the AAP-SD associations by using FAERS. In this study, we report for the first time a significant association between aripiprazole and SD based on real-world data. The study suggests that different AAPs have varying levels of association with SD, and the D2, D3, and 5-HT1A receptor occupancy may contribute to potential mechanisms. The findings of this study warrant further validation of more studies and clinical causality assessment.

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“…In light of this trend, it is important to conduct post-marketing surveillance studies to ensure the safety of these drugs. Previous studies have used the FAERS database to elucidate the relationship between SSRIs and suicidality 19 , mania 20 , and postpartum bleeding 21 . Some case reports have suggested that using SSRIs could lead to rhabdomyolysis, a potentially life-threatening syndrome.…”

Section: Discussionmentioning

confidence: 99%

Exploring the association between selective serotonin reuptake inhibitors and rhabdomyolysis risk based on the FDA pharmacovigilance database

Wang

Lin

et al. 2023

Sci Rep

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Rhabdomyolysis is a syndrome potentially fatal and has been associated with selective serotonin reuptake inhibitors (SSRIs) treatment in a few case reports. Herein, we purpose to establish the correlation between SSRIs use and rhabdomyolysis using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. We conducted an analysis on reports that were submitted to the FAERS database during the period between January 1, 2004, and December 31, 2022. Four algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM), were employed to quantify the signals of rhabdomyolysis associated with SSRIs. In total, 16,011,277 non-duplicated reports were obtained and analyzed. Among 33,574 reports related to rhabdomyolysis, SSRIs were classified as primary suspected drug in 889 cases. Disproportionality analysis identified a positive signal between rhabdomyolysis and SSRIs (ROR: 2.86, 95% CI 2.67–3.05; PRR: 2.84, χ2: 1037.16; IC0.25 = 1.39; EBGM0.5 = 2.64). Among six SSRIs, fluvoxamine had the strongest signal (ROR: 11.64, 95% CI 8.00–16.93; PRR: 11.38, χ2: 265.51; IC0.25 = 2.41; EBGM0.5 = 8.31), whereas no significant signal of rhabdomyolysis was detected for paroxetine (ROR: 1.83, 95% CI 1.55–2.15; PRR: 1.82, χ2: 53.82; IC0.25 = 0.73; EBGM0.5 = 1.59). After excluding cases co-administered with statins, the signal of rhabdomyolysis associated with SSRIs remains significant. Our analysis reveals that there are differences in safety signals among six SSRIs in respect to the risk of rhabdomyolysis, with fluvoxamine displaying the highest risk signal, while paroxetine did not show a significant signal. Given the potentially lethal nature of rhabdomyolysis, healthcare professionals should inform patients of the potential risk of rhabdomyolysis associated with SSRIs prior to initiating treatment.

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Selective serotonin reuptake inhibitors and manic switch: A pharmacovigilance and pharmacodynamical study

Cited by 4 publications

References 42 publications

Exploring the underlying mechanisms of drug‐induced impulse control disorders: a pharmacovigilance‐pharmacodynamic study

Exploring the underlying mechanisms of drug‐induced impulse control disorders: a pharmacovigilance‐pharmacodynamic study

The atypical antipsychotics and sexual dysfunction: a pharmacovigilance-pharmacodynamic study

Exploring the association between selective serotonin reuptake inhibitors and rhabdomyolysis risk based on the FDA pharmacovigilance database

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