Stereo‐Psychopharmacology: The Case of Citalopram and Escitalopram

Ng, Isaac; Greenblatt, H. Karl; Greenblatt, David J.

doi:10.1002/cpdd.293

Cited by 7 publications

(4 citation statements)

References 52 publications

(95 reference statements)

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“…The racemate citalopram was associated with an increased risk, whereas the S‐enantiomer escitalopram had a low ROR value. Different therapeutic efficacy of the two isomers can be explained with different affinity of the S‐ and the L‐enantiomer to the serotonin receptor target of the drug [37]. However, with respect to ADRs, a disproportionality analysis did not reveal any difference between racemate and enantiomer [38] which might be due to the fact that that study compared only broad classes of ADRs (e.g., cardiovascular, renal, neuropsychiatric, hematological).…”

Section: Discussionmentioning

confidence: 99%

Worsening of myasthenia due to antiepileptic, antipsychotic, antidepressant, and sedative medication: An estimation of risk based on reporting frequency

Trillenberg

Katalinic

Junghanns

et al. 2021

Euro J of Neurology

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Background and purpose Many drugs can worsen myasthenia symptoms. The clinician usually relies on cautionary lists compiled according to case reports. We intended to provide a quantitative basis for a risk comparison within the groups of antiepileptic, antidepressant, neuroleptic, and sedative drugs. Methods We extracted adverse drug reaction (ADR) counts (total and myasthenia related) for drugs from these groups and calculated the reporting odds ratio (ROR) within the drug groups from the World Health Organization pharmacovigilance database. For a given drug, the ROR was increased above 1 if the proportion of myasthenia‐related ADRs for this drug was larger than the same proportion for the rest of drugs in that same group. If the 95% confidence interval of ROR was >1, this was taken as a signal for a higher risk of the given drug as compared to the average of the respective group. Results Gabapentin, sertraline, citalopram, lithium, and amisulpride had a signal for the ROR to be increased above 1 within their respective groups. Bupropion, desvenlafaxine, duloxetine, escitalopram, and paroxetine had ROR values <1. For all other drugs, 1 was within the ROR confidence interval. Conclusions For gabapentin and lithium, the analysis of RORs confirmed case reports and cautionary lists. For a number of antidepressant drugs associated with a higher‐than‐average risk, no case reports exist substantiating our results. For these drugs, special attention should be paid to this risk. The remarkable difference between citalopram and escitalopram could prompt experimental work to confirm differential influence of the two preparations on neuromuscular transmission.

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Section: Discussionmentioning

confidence: 99%

Worsening of myasthenia due to antiepileptic, antipsychotic, antidepressant, and sedative medication: An estimation of risk based on reporting frequency

Trillenberg

Katalinic

Junghanns

et al. 2021

Euro J of Neurology

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“…Os membros da família da isoenzima CYP2C19 são um dos principais responsáveis pelo metabolismo dos medicamentos utilizados no tratamento de pacientes com transtorno depressivo maior, dentre eles o citalopram e escitalopram (3). Polimorfismos do gene CYP2C19, que codifica essa família de isoenzima, têm sido relacionados com alterações na metabolização desses medicamentos, comprometendo assim a sua eficácia 19 .…”

Section: Resultsunclassified

Qualidade De Vida, Sintomas De Depressão E Adesão Ao Tratamento Em Pacientes Com Transtorno Depressivo Maior

Andrade¹,

Souza²,

Amaral³

et al. 2021

REV. CIÊNC. PLURAL

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Introdução: Pacientes com depressão maior geralmente respondem ao tratamento com medicamentos antidepressivos, no entanto em 10% a 30% dos casos há apenas uma resposta parcial ou nenhuma resposta, entre os fatores que podem influenciar encontra-se o perfil das enzimas hepáticas metabolizadoras dos antidepressivos, tal como a CYP2C19. Objetivo: Investigar polimorfismos CYP2C19*2 ou CYP2C19*17 em pacientes com transtorno depressivo maior (TDM) tratados com citalopram ou escitalopram e verificar associações com adesão ao tratamento, sintomas de depressão e qualidade de vida. Metodologia: Trata-se de um estudo de série de casos realizado com 29 pacientes com TDM. Amostras de sangue foram coletadas para genotipagem de CYP2C19 por discriminação alélica TaqMan®. Foram coletados dados sobre perfil demográfico e socioeconômico, adesão ao tratamento (escala de Morisky), sintomas de depressão (escala de Hamilton) e qualidade de vida (WHOQoL-BREF). Resultados: Havia quatro pacientes (13.8%) com polimorfismo CYP2C19*2 e 10 (34.4%) com CYP2C19*17. Houve maior prevalência de CYP2C19*17 em comparação com CYP2C19*2 (p>0.05). Em geral, nenhuma associação significativa de características socioeconômicas, demográficas e clínicas com os genótipos CYP2C19. A adesão moderada ao tratamento foi predominante nos pacientes CYP2C19*2 e CYP2C19*17 (p>0.05). Não foi observada associação entre sintomas de depressão e polimorfismos genéticos (p>0.05). Uma associação significativa entre o genótipo polimórfico CC do CYP2C19*17 com a satisfação com a saúde, enquanto o genótipo CT foi associado ao estado “nem satisfeito/nem insatisfeito” (p<0.05). A maioria dos indivíduos CYP2C19*2 e CYP2C19*17 relatou “necessidade de melhorar” em relação aos domínios físico, psicológico, social e ambiental (p>0.05). Conclusões: Os casos estudados apresentaram maior prevalência do polimorfismo CYP2C19*17, com moderada adesão ao tratamento. Muitos pacientes, mesmo sob efeito da medicação, apresentaram sintomas de depressão intensos a moderados, e relataram prejuízo na satisfação com a saúde.

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“…Dysregulation of the serotonin system underlies depressive disorders, and 5-HT1A receptor dysfunction may play a crucial role (Drevets et al, 2000; Hirvonen et al, 2008; Żmudzka et al, 2018). Several studies confirmed the decreased density of 5-HT1A receptors in people suffering from major depression (Savitz et al, 2009; Wang et al, 2016). The animal studies confirm these findings, as 5-HT1A-receptor-knock-out mice exhibited anxiety and depressive-like behaviours (Gross et al, 2000, 2002; Klemenhagen et al, 2006; Li et al, 2012; Olivier et al, 2001; Parks et al, 1998; Richardson-Jones et al, 2011).…”

Section: Introductionmentioning

confidence: 80%

“…One of the enantiomers may possess more potent activity, no pharmacological effect, or even exhibit toxic properties (Brooks et al, 2011). Among antidepressants, escitalopram and esketamine show better pharmacological profile than their R-enantiomers (Molero et al, 2018; Ng et al, 2016). Our studies, however, showed that this is not that pronounced for HBK-1 (R, S) and its enantiomers, HBK-1 (R) and HBK-1 (S).…”

Section: Discussionmentioning

confidence: 99%

The antidepressant-like activity of chiral xanthone derivatives may be mediated by 5-HT1A receptor and β-arrestin signalling

et al. 2020

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Background: Our previous studies showed that xanthone derivatives with N-(2-methoxyphenyl)piperazine fragment have an affinity to the 5-HT1A receptor and show antidepressant-like properties in rodents. In this study, we tested three xanthone derivatives, HBK-1 (R, S) and its enantiomers, in which we increased the distance between the piperazine and xanthone fragments by using a hydroxypropoxy linker. We hypothesized that this would increase the binding to the 5-HT1A receptor and consequently, pharmacological activity. Aims: We aimed to assess the in vitro and in vivo pharmacological activity of the xanthone derivatives. Methods: We evaluated the in vitro affinity for serotonin 5-HT1A and 5-HT2A receptors and serotonin transporter. We also determined the intrinsic activity at the 5-HT1A receptor. We investigated the antidepressant-like properties and safety after acute administration (dose range: 1.25–20 mg/kg) using the forced swim, tail suspension, locomotor activity, rotarod and chimney tests in mice. We also evaluated the basic pharmacokinetic parameters. Results: Our results indicated that the compounds showed a high affinity for the 5-HT1A receptor but very weak antagonistic properties in the Ca2+ mobilization assay; however, they showed significant agonistic properties in the β-arrestin recruitment assay. In both behavioural tests the studied xanthone derivatives showed antidepressant-like activity. Pre-treatment with p-chlorophenylalanine or WAY-100635 abolished their antidepressant-like activity. None of the compounds caused motor impairments at antidepressant-like doses. The racemate penetrated the blood–brain barrier and had a relatively high bioavailability after intraperitoneal administration. Conclusions: Xanthone derivatives with N-(2-methoxyphenyl)piperazine fragment and hydroxypropoxy linker show increased binding to the 5-HT1A receptor and may represent an attractive putative treatment candidate for depression.

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Stereo‐Psychopharmacology: The Case of Citalopram and Escitalopram

Cited by 7 publications

References 52 publications

Worsening of myasthenia due to antiepileptic, antipsychotic, antidepressant, and sedative medication: An estimation of risk based on reporting frequency

Worsening of myasthenia due to antiepileptic, antipsychotic, antidepressant, and sedative medication: An estimation of risk based on reporting frequency

Qualidade De Vida, Sintomas De Depressão E Adesão Ao Tratamento Em Pacientes Com Transtorno Depressivo Maior

The antidepressant-like activity of chiral xanthone derivatives may be mediated by 5-HT1A receptor and β-arrestin signalling

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