Ketamine but not glycine potentiates antidepressant like action of citalopram in mice exposed to chronic mild stress

Background: The present study was designed to investigate the effect of citalopram, ketamine, glycine and their combinations on animal models of depression. Methods: Swiss Albino male mice were subjected to chronic mild stress for 6 weeks for inducing depression, and randomly divided into different groups: citalopram (5 and 10 mg/kg), ketamine (17.5 and 35 mg/kg), glycine (50 and 100 mg/kg), ketamine (17.5 mg/kg) + citalopram (5 mg/kg) and ketamine (17.5 mg/kg) + glycine (50 mg/kg). Two behavioural tests were utilized for the assessment of depression, namely tail suspension test (TST) and forced swim test (FST). Immobility time was recorded for 6 min, before and after administration of drug. Results: Citalopram (10 mg/kg) administration caused significant decrease in the immobility time in TST model only but not in FST. Citalopram (5 mg/kg) and ketamine (17.5 mg/kg) caused insignificant decrease in immobility time in both the models. Moreover, ketamine in combination with Citalopram significantly reduced the immobility time in both the models. Glycine at a dose of 100 mg/kg (but not 50 mg/kg) significantly increased the immobility time in both the models as compared to control group. Further, ketamine when administered with glycine caused increase in the immobility time on both the paradigms, though insignificant. Conclusions: Ketamine demonstrated antidepressant like action in both TST and FST models. Moreover, it potentiated the antidepressant effect of citalopram that might be due to the role of NMDA receptors.

ANTIDEPRESSANT-LIKE ACTIVITY OF METHANOLIC EXTRACT OF WITHANIA QARAITICA IN MICE

Objective: The goal of the present study was to assess the antidepressant-like action of Withania qaraitica in two behavioral animal models, the forced-swimming test (FST) and tail suspension test (TST) in mice.Methods: Withania qaraitica methanolic extract was prepared by the maceration. The antidepressant activity was measured by the forced-swimming test (FST) using C57BL/6 mice and the tail suspension test (TST) using BALB/c mice. Mice were divided into three groups: control (DMSO), standard (citalopram and desipramine), and Withania qaraitica methanolic extract (n = 6 per group). Drugs were injected (1 ml/100 g) intraperitoneally (i. p.). Data were evaluated using analysis of variance, followed by LSD post-hoc tests, where *p<0.001 was considered significantly different from the vehicle control. The data are expressed as mean±SEM.Results: In both the FST and the TST, antidepressant-positive controls citalopram and desipramine significantly reduced the time of immobility compared to vehicle control (p<0.001). The methanolic extract of Withania qaraitica at the dose of 40 mg/kg significantly reduced the immobility times with respect to vehicle control as well as lower doses of the same extract (10 and 20 mg/kg) in FST (p<0.001). In a similar fashion, the methanolic extract of Withania qaraitica at the dose of 40 mg/kg significantly decreased the duration of immobility in TST (p<0.005).Conclusion: The current results show the antidepressant-like activity of Withania qaraitica in mice. This observation warrants additional studies to identify the underlining mechanism by which Withania qaraitica produces antidepressant-like effects.

Meta-analysis of the effects of gene polymorphism on the efficacy and safety of citalopram/escitalopram / 中国药房

OBJECTIVE To evaluate the effects of gene polymorphism on the efficacy and safety of citalopram/escitalopram， and to provide evidence-based reference for precision medication. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang data and SinoMed， clinical studies about the association of gene polymorphism with efficacy and safety of citalopram/escitalopram were collected. Meta-analysis was performed with RevMan 5.3 software after literature screening， data extraction and quality evaluation based on Newcastle-Ottawa scale. RESULTS Totally 35 pieces of literature were included， all of which were cohort studies， with a total of 9 836 patients. Meta-analysis showed that the SLC6A4 gene 5-serotonin transporter linked polymorphic region （HTTLPR） LL genotype was associated with high response rate of citalopram/escitalopram [LS/SS vs. LL： OR＝0.47， 95%CI （0.22， 0.98）， P＝0.05]； results of subgroup analysis suggested a higher correlation in white people with LL genotype and escitalopram； there was no significant correlation of HTTLPR genotype with remission rate [LS/SS vs. LL： OR＝ 0.92，95%CI（0.77， 1.10）， P＞0.05； SS vs. LL/LS：OR＝0.73， 95%CI（0.45， 1.19）， P＞0.05] or overall incidence of ADR in patients with gene SLC6A4； but high expression of rs25531 LA was significantly associated with reduced incidence of ADR（P＜ 0.05）. CYP2C19*2/*3 allele was significantly associated with slowed metabolism， higher response rate and increased incidence of ADR. CONCLUSIONS HTTLPR LL genotype is associated with the increased response rate of citalopram/escitalopram， but no significant correlation with safety is found， while CYP2C19*2/*3 allele is significantly associated with higher response rate and reduced tolerability.

Qualidade de vida, sintomas de depressão e adesão ao tratamento em pacientes com trantorno depressivo maior / Quality of life, depression symptoms and adherence to treatment in patients with major depressive disorder / Calidad de vida, síntomas depresión y adhesión al tratamiento en pacientes con trastorno depresivo mayor

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:Caracterizar os indivíduos quanto ao perfil genético dospolimorfismos CYP2C19*2 ou CYP2C19*17 em pacientes com transtorno depressivo maior (TDM) tratados com citalopram ou escitalopram e compará-los em relação a adesão ao tratamento, sintomas de depressão e qualidade de vida.Metodologia:Trata-se de um estudo transversal realizado com 29 pacientes com TDM. Amostras de sangue foram coletadas para genotipagem de CYP2C19 por discriminação alélica TaqMan®. Após caracterização do perfil genético, os indivíduos foram comparados quanto aos dados demográfico e socioeconômico, adesão ao tratamento (TestedeMorisky-Green),sintomas de depressão (escala de Hamilton) e qualidade de vida (WHOQoL-BREF).Resultados:Quatro pacientes (13.8%) apresentaram polimorfismo para CYP2C19*2 e 10 pacientes (34.4%) para CYP2C19*17, com maior prevalência de CYP2C19*17 (p>0.05). Nenhuma associação significativa de características socioeconômicas, demográficas e clínicas entre os genótipos do CYP2C19.No TestedeMorisky-Green, aadesão 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 de qualidade de vida físico, psicológico, social e ambiental (p>0.05).Conclusões:Os pacientes apresentaram maior prevalência do polimorfismo CYP2C19*17, com moderada adesão ao tratamento. Alguns pacientes, mesmo sob efeito da medicação, apresentaram sintomas de depressão moderado a intenso e relataram uma indefinição na satisfação da sua qualidade de vida (AU).

Introduction:Patients with major depression usually respond to treatment with antidepressant drugs, however in 10% to 30% of cases there is only a partial response or no response, among the factors that can influence is the profile of liver enzymes metabolizing antidepressants, such as CYP2C19.Objective:To characterize the individuals regarding the genetic profile ofCYP2C19*2or CYP2C19*17 polymorphisms in patients with major depressive disorder (MDD) treated with citalopram or escitalopram, and to compare themaccording to treatment adherence, symptoms of depression and quality of life.Methodology:This is cross-sectionalstudy carried out with 29 patients with MDD. Blood samples were collected for CYP2C19 genotyping by TaqMan® allelic discrimination. After characterization of the genetic profile, the individuals were compared regarding the demographic and socioeconomic data, treatment adherence (Morisky-GreenTest), symptoms of depression (Hamilton scale) and quality of life (WHOQoL-BREF).Results:Four patients showed (13.8%) CYP219*2 and 10 patients (34.4%) CYP219*17 polymorphisms.,withhigher prevalence of CYP219*17 (p>0.05). No association between socioeconomic, demographic, and clinical features with CYP2C19 genotypes was observed. In Morisky-GreenTest, moderate adherence to treatment was predominant for CYP2C19*2 and CYP219*17 patients (p>0.05). No statistically significant association was observed between symptoms of depression and genetic polymorphisms (p>0.05). A significant association between polymorphic CC genotype of CYP219*17 with health satisfaction, while the CT genotype was associated with "neither satisfied/nor dissatisfied" status (p<0.05). Most of the CYP2C19*2 and CYP2C19*17 subjects reported "need to improve" or "regular" regarding physical, psychological, social, and environmental domainsof quality of life(p>0.05).Conclusions:The patients showed a higher prevalence of CYP219*17 polymorphism, with moderate treatment adherence. Some subjects, even under the effect of the medication, presented moderate to intense symptoms of depression, and reported a lack of definition in the satisfaction of their quality of life (AU).

Introducción:Los pacientes con depresión mayor responder al tratamiento con antidepresivos, en 10% al 30% de los casos existe una respuesta parcial o nula, entre los factores que pueden influir se encuentra el perfil de enzimas hepáticas metabolizadoras de antidepresivos, como CYP2C19.Objetivo: Caracterizar a los individuos en cuanto al perfil genético depolimorfismos CYP2C19 *2 o CYP2C19 * 17 en pacientes con trastorno depresivo mayor (TDM) tratados con citalopram o escitalopram y compararlos en relaciónpara la adherencia al tratamiento, síntomas de depresión y la calidad de vida.Metodología: Estudio transversalcon 29 pacientes con TDM. Se recogieron muestras de sangre para la determinación del genotipo CYP2C19 mediante discriminación alélica TaqMan®, los individuos fueron comparados en cuanto a los datosdemográficosy socioeconómicos, adherencia (Prueba de Morisky-Green), síntomas de depresión (escala de Hamilton) y calidad de vida (WHOQoL-BREF).Resultados: Cuatro pacientes (13,8%) con polimorfismo CYP2C19*2 y 10 (34,4%) con CYP2C19 * 17,(p> 0,05). No existe una asociación significativa de las características socioeconómicas, demográficas y clínicas con los genotipos CYP2C19. La adherencia moderada al tratamiento fue predominante en los pacientes con CYP2C19*2 y CYP2C19*17 (p> 0,05). No hubo asociación entre síntomas de depresión y polimorfismos genéticos (p> 0.05). Una asociación significativa entre el genotipo polimórfico CYP2C19 * 17 CC con la satisfacción con la salud, mientras que el genotipo CT se asoció con el estado "ni satisfecho / no insatisfecho" (p <0.05). La mayoría de CYP2C19 * 2 y CYP2C19 * 17 individuos informaron "necesidad de mejorar" en relación con los dominios físico, psicológico, social y ambientalde calidad de vida(p> 0,05).Conclusiones: Los pacients mostraron una mayor prevalencia del CYP2C19 * 17, con adherencia moderada al tratamiento, síntomas de depresión moderada a intensay informaron una falta de definición en la satisfacción de su calidad de vida (AU).

The effectiveness of melissa officinalis l. Versus citalopram on quality of life of menopausal women with sleep disorder: a randomized double-blind clinical trial

Abstract Objective The present study aimed to assess the effect of Melissa Officinalis L. (a combination of lemon balm with fennel fruit extract) compared with citalopram and placebo on the quality of life of postmenopausal women with sleep disturbance. Methods The present study is a randomized, double-blind, placebo clinical trial among 60 postmenopausal women with sleep disturbance who were referred to a university hospital from 2017 to 2019. The participants were randomized to receive M. Officinalis L. (500 mg daily), citalopram (30 mg) or placebo once daily for 8 weeks. The Menopause-Specific Quality of Life (MENQOL) questionnaire was self-completed by each participant at baseline and after 8 weeks of the intervention and was compared between groups. Results The mean for all MENQOL domain scores were significantly improved in the M. Officinalis L. group compared with citalopram and placebo (p < 0.001). The mean ± standard deviation (SD) after 8 weeks in the M. Officinalis L., citalopram and placebo groups was 2.2 ± 0.84 versus 0.56 ± 0.58 versus 0.36 ± 0.55 in the vasomotor (p < 0.001), 1.02 ± 0.6 versus 0.28 ± 0.2 versus 0.17 ± 0.1 in the psychomotor-social (p < 0.001), 0.76 ± 0.4 versus 0.25 ± 0.1 versus 0.11 ± 0.1 in the physical and 2.3 ± 1.0 versus 0.35 ± 0.5 versus 0.41 ± 0.5 in the sexual domain, respectively. Conclusions The results revealed that M. Officinalis L. may be recommended for improving the quality of life of menopausal women with sleep disturbance. Trial registration The present study was registered by the name "Comparison of the efficacy of citalopram and compound of Asperugo procumbens and foeniculum vulgare in treatment of menopausal disorders" with the code IRCT2013072714174N1 in the Iranian Registry of Clinical Trials (IRCT).

Application Of Central Composite Design For Citalopram Hydrogen Bromide Mouth Dissolving Films

Citalopram is an antidepressant used for treating major depressive disorder. In the current work Citalopram HBr is formulated as mouth dissolving film with enhanced drug dissolution. The Central Composite Design (CCD), employed to examine the effects of amount of HPMC E50 (A), amount of maltodextrin (B) and amount of glycerol (C) on response variables tensile strength, disintegration time and cumulative % drug release. 27 formulations prepared according to CCD and evaluated for physicochemical parameters and in vitro dissolution studies. Citalopram HBr mouth dissolving films formulated by employing solvent-casting method using HPMC E50, maltodextrin and glycerol, optimized for the effective dosage of superdisintegrants. The formulation CF21 with maximum tensile strength of 67.21±1.31 gm, least disintegration time of 9±1.60 sec and highest drug release of 98.41±1.81% is chosen optimal formulation with maximum content uniformity and folding endurance. It is evident from the above results that the developed formulation can be an innovative dosage form to improve the drug delivery, quick onset of action as well as improve patient compliance in the effective management of depression.

Pharmacokinetics and Brain Delivery of Citalopram Hydrobromide Thermosensitive Nasal Gel in Rats / 中国药学杂志

OBJECTIVE: To investigate the pharmacokinetics of citalopram hydrobromide(CTH)thermosensitive nasal gel and further evaluate its brain delivery in rats. METHODS: The concentrations of CTH in rat plasma and brain tissue were determined by HPLC method. With intragastric administration (ig) of CTH solution as control, CTH thermosensitive nasal gel was intranasally given to rats and the concentrations of CTH in plasma and brain tissues were then determined. Moreover, the main pharmacokinetic parameters of CTH in plasma and brain tissues such as tmax, ρmax,relative bioavailability (Fr) and drug targeting efficiency (DTE) were estimated. RESULTS: Main pharmacokinetic parameters of CTH following nasal and ig administration to rats such as tmax and ρmax were 5 and 45 min, 2 152.86 and 589.68 ng•mL-1 in plasma, and 5 and 45 min, 17 660.56 and 1 171.68 ng•g-1 in brain tissue, respectively. Finally, the Fr and DTE of CTH thermosensitive nasal gel were found to be 184.91% and 250.03%, respectively. CONCLUSION: CTH thermosensitive nasal gel may be an ideal non-oral new dosage form with many advantages such as rapid in vivo absorption, high bioavailability and obvious brain delivery characteristics.

Formulation Optimization of Citalopram Hydrobromide Thermosensitive Nasal Gel and Its In Vitro Properties / 中国药学杂志

OBJECTIVE: To optimize the formulation of citalopram hydrobromide (CTH ) thermosensitive nasal gel and further evaluate its in vitro properties. METHODS: With gelling temperature and gelling time as evaluating indexes, central composite design-response surface and single factor experimental design method were used to optimize the formulation of CTH thermosensitive nasal gel by using poloxamer 407(F127) and carbomer 940 (CP940) as gel materials. Meanwhile, nasal mucosa permeation enhancer for CTH was then sieved by using Franz diffusion cell and ex vivo sheep nasal mucosa as experimental model. Finally, CTH thermosensitive nasal gel was prepared with cold method and then its in vitro properties was evaluated. In vitro cumulative erosion and cumulative release rate of the drug thermosensitive nasal gel were investigated by membrane-free dissolution method and dialysis membrane method, respectively. Moreover, the effect of temperature and pH on the viscosity of the drug nasal gel formulation was also evaluated. RESULTS: The optimal formulation of the thermosensitive nasal gel consisted of CTH 8.0%, F127 20.27%, CP940 0.17%, DM-β-CD 3.0%, ethylparaben 0.05% and distilled water. The gelling temperature, gelling time and pH of the drug thermosensitive nasal gel were found to be about 32.5 ℃,42 s and 5.0, respectively. The in vitro cumulative erosion and cumulative release percentage were both greater than 90% in 55 min and furthermore there was good linear correlation between these two parameters (r=0.998 6). Additionally, in vitro cumulative release of the drug from the gel formulation was determined to be 92% within 8 h, which conformed to Higuchi kinetic equation. Furthermore, the viscosity of the drug nasal gel was influenced by temperature as well as pH in different extent. CONCLUSION: The optimized formulation of the CTH thermosensitive nasal gel with central composite design-response surface method and single factor design method shows suitable gelling temperature, gelling time, pH value for nasal preparation and obvious in vitro drug sustained release characteristics.

Lavender and dodder combined herbal syrup versus citalopram in major depressive disorder with anxious distress: A double-blind randomized trial / 中西医结合学报

BACKGROUND@#Major depressive disorder (MDD) accompanied by anxious distress is a chronic and disabling disorder. Its conventional drug therapies often have low patient compliance due to drug-related side effects. In Persian medicine, lavender-dodder syrup is one formula often recommended for such disorders.@*OBJECTIVE@#This study compares the effects of lavender-dodder syrup to the standard drug, citalopram, for treating MDD with anxious distress.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This six-week, double-blind, randomized, clinical trial was carried out in a psychiatric outpatient clinic. During the six-week intervention period, patients in citalopram group received citalopram tablets 20 mg/d plus 5 mL placebo syrup every 12 h; patients in group B received placebo tablets once daily plus 5 mL of lavender-dodder herbal syrup every 12 h.@*MAIN OUTCOME MEASURES@#Primary outcome measures, depression and anxiety, were evaluated using the Hamilton Depression/Anxiety Rating Scales, and were scored at the beginning of the study and at weeks three and six. Secondary outcome measures including response to treatment and remission rates were also compared between the two groups.@*RESULTS@#Fifty-six participants with MDD and anxious distress were randomly assigned to two groups. Mean depression scores significantly decreased in citalopram and herbal groups at weeks three and six (time effect: P < 0.001), although the observed changes were not significantly different between the groups (intervention effect: P = 0.61). Mean anxiety scores were not significantly different between the two groups at week three (P = 0.75). However, at the end of week six, the observed decrease was significantly higher in the herbal syrup group than the citalopram group (intervention effect: P = 0.007).@*CONCLUSION@#The herbal syrup is an effective and tolerable supplement for treating MDD with anxious distress.@*TRIAL REGISTRATION NUMBER@#IRCT2016102430459N1 on Iranian Registry of Clinical Trials.

Lavender and dodder combined herbal syrup versus citalopram in major depressive disorder with anxious distress: A double-blind randomized trial / 中西医结合学报

BACKGROUND@#Major depressive disorder (MDD) accompanied by anxious distress is a chronic and disabling disorder. Its conventional drug therapies often have low patient compliance due to drug-related side effects. In Persian medicine, lavender-dodder syrup is one formula often recommended for such disorders.@*OBJECTIVE@#This study compares the effects of lavender-dodder syrup to the standard drug, citalopram, for treating MDD with anxious distress.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This six-week, double-blind, randomized, clinical trial was carried out in a psychiatric outpatient clinic. During the six-week intervention period, patients in citalopram group received citalopram tablets 20 mg/d plus 5 mL placebo syrup every 12 h; patients in group B received placebo tablets once daily plus 5 mL of lavender-dodder herbal syrup every 12 h.@*MAIN OUTCOME MEASURES@#Primary outcome measures, depression and anxiety, were evaluated using the Hamilton Depression/Anxiety Rating Scales, and were scored at the beginning of the study and at weeks three and six. Secondary outcome measures including response to treatment and remission rates were also compared between the two groups.@*RESULTS@#Fifty-six participants with MDD and anxious distress were randomly assigned to two groups. Mean depression scores significantly decreased in citalopram and herbal groups at weeks three and six (time effect: P < 0.001), although the observed changes were not significantly different between the groups (intervention effect: P = 0.61). Mean anxiety scores were not significantly different between the two groups at week three (P = 0.75). However, at the end of week six, the observed decrease was significantly higher in the herbal syrup group than the citalopram group (intervention effect: P = 0.007).@*CONCLUSION@#The herbal syrup is an effective and tolerable supplement for treating MDD with anxious distress.@*TRIAL REGISTRATION NUMBER@#IRCT2016102430459N1 on Iranian Registry of Clinical Trials.

Effect of citalopram on miRNA-16/serotonin transporter pathway in peripheral blood of patients with depression / 上海交通大学学报（医学版）

Objective • To discuss the effects of citalopram on miRNA-16/serotonin transporter (SERT) pathway in peripheral blood of the patients with depression. Methods • Forty-five patients with depression without medication (untreated group), 32 patients with depression treated with medicine(drug treated group) and 32 healthy people (control group) were enrolled in the study. Hamilton Depression Scale-17 items were used to evaluate the depressive symptoms. The expression level of plasma miRNA-16 was detected by fluorescence quantitative PCR, and the level of SERT protein in platelets was detected by Western blotting. Fourteen of the baseline patients who were treated with citalopram were followed up for 2 months. After the follow-up, the evaluation of HAMD-17, the detection of miRNA-16 and SERT protein were conducted. Results • There was no significant difference in the expression level of plasma miRNA-16 among the three groups (F=0.421, P=0.657). There was no significant difference of SERT protein expression in the platelets among the three groups (F=0.112, P=0.894). The follow-up study showed that the HAMD-17 score decreased after 2 months (Z=.3.187, P=0.001), the average expression level of plasma miRNA-16 increased (t=2.455, P=0.032), and the expression of SERT protein in the platelets did not change (t=.0.750, P=0.470) in 14 patients who were treated with citalopram. Conclusion • Citalopram, a serotonin reuptake inhibitor, can down-regulate the expression of plasma miRNA-16 in patients with depression, and the decrease of the platelet serotonin is not caused by the decrease of SERT protein on platelet membrane, but may be related to the decrease of the SERT function.

Which of available selective serotonin reuptake inhibitors (SSRIs) is more effective in treatment of premature ejaculation? A randomized clinical trial

ABSTRACT Purpose: To compare the efficacy and safety of available selective serotonin reuptake inhibitors (SSRIs) in order to find the most effective drug with the least number of side effects in treatment of premature ejaculation (PE). Materials and Methods: This study was a randomized clinical trial. Four hundred and eighty patients with PE in the 4 groups referred to Imam Reza hospital Tehran, Iran from July 2018 to February 2019 were enrolled in the study. The patients received sertraline 50mg, fluoxetine 20mg, paroxetine 20mg and citalopram 20mg, every 12 hours daily. The intravaginal ejaculatory latency time (IELT) before treatment, fourth and eighth weeks after treatment was recorded by the patient's wife with a stopwatch. Results: Mean IELT before, 4 and 8 weeks after treatment in four groups were: sertraline 69.4±54.3, 353.5±190.4, 376.3±143.5; fluoxetine 75.5±64.3, 255.4±168.2, 314.8±190.4; paroxetine 71.5±69.1, 320.7±198.3, 379.9±154.3; citalopram 90.39±79.3, 279.9±192.1, 282.5±171.1 seconds, respectively. The ejaculation time significantly increased in all groups (p <0.05), but there was no significant difference between the groups (P=0.75). Also, there was no significant difference in drugs side effects between groups (p >0.05). The most common side effects were drowsiness and dyspepsia, which were not severe enough to cause discontinuation of the drug. Conclusions: All available SSRIs were effective and usually had no serious complications. In patients who did not respond to any of these drugs, other SSRI drugs could be used as a salvage therapy.

Neonatal exposure to citalopram increases pyramidal and granular cell density in dorsal hippocampus of male but not female adult rats: a quantitative Nissl study / La exposición neonatal al citalopram aumenta la densidad de las células piramidales y granulares en el hipocampo dorsal de ratas adultas macho pero no en hembras: un estudio cuantitativo con tinción de Nissl

Antidepressants use during pregnancy was associated with an increased risk of autism spectrum disorders. Animal models based on early life alterations in serotonin availability replicate some of the anatomical and behavioral abnormalities observed in autistic individuals. In recent years there has been a growing interest in the possible role of the hippocampus in autism. The aim of study is to examine the effects of neonatal antidepressant (CTM) exposure during a sensitive period of brain development on pyramidal and granule cells density of hippocampal formation. We examined the pyramidal and granular cells density of dorsal hippocampus using Nissl stained sections obtained from neonatal citalopram (CTM) exposed rats (5 mg/kg, twice daily, s.c.), from postnatal day 8 to 21 (PN8-21), saline and non-exposed rats. The density of pyramidal cells was significantly increased by 10.2 % in CA1, 10.6 % in CA3 and 13.2 % in CA4 in CTM treated compared with non-treated or saline treated animals (p<0.0001). The density of granule cells in the dentate gyrus was significantly increased by 12.0 % in CTM treated compared with non-treated or saline treated animals (p<0.0001). These findings were obtained only from male rats, suggesting a sexual dimorphism in neural development after SSRI exposure. These data suggest that the neonatal exposure to CTM may induce long-lasting changes in the hippcampal formation in adults, and such effects appear to preferentially target males.

El uso de antidepresivos durante el embarazo se asoció con un mayor riesgo de trastornos del espectro autista. Los modelos animales basados en alteraciones tempranas de la vida en la disponibilidad de serotonina replican algunas de las anomalías anatómicas y de comportamiento observadas en individuos autistas. En los últimos años ha habido un interés creciente en el posible papel del hipocampo en el autismo. El objetivo del estudio fue examinar los efectos de la exposición al antidepresivo neonatal (CTM) durante un período sensible del desarrollo cerebral en la densidad de las células piramidales y granulares de la formación del hipocampo. Examinamos la densidad de las células piramidales y granulares del hipocampo dorsal utilizando secciones teñidas con Nissl obtenidas de ratas expuestas al citalopram neonatal (CTM) (5 mg / kg, dos veces al día, sc), desde el día postnatal 8 a 21 (PN8-21), solución salina y ratas no expuestas. La densidad de células piramidales se incrementó significativamente en un 10,2 % en CA1, 10,6 % en CA3 y 13,2 % en CA4 en CTM tratados en comparación con animales no tratados o tratados con solución salina (p <0,0001). La densidad de células granulares en el giro dentado aumentó significativamente en un 12,0 % en los animales tratados con CTM en comparación con los animales no tratados o tratados con solución salina (p <0,0001). Estos hallazgos se obtuvieron solo en ratas macho, lo que sugiere un dimorfismo sexual en el desarrollo neural después de la exposición a ISRS. Estos datos sugieren que la exposición neonatal a la CTM puede inducir cambios de larga duración en la formación del hipocampo en adultos, y estos efectos parecen dirigirse preferentemente a los machos.

Effects of benzalkonium bromide and citalopram on the thickness of corneal epithelium and full-thickness of the cornea in mice / 眼科新进展

Objective To explore the effects of benzalkonium bromide and citalopram on the corneal epithelium and corneal thickness of mice using optical coherence tomography angiography (OCTA).Methods Together 60 mice were randomly divided into 5 groups (group A,B,C,D and E;n =12),with group A left untreated,group B receiving PBS eye drops,group C given benzalkonium bromide eye drops,group D undergoing intraperitoneal administration of citalopram suspension,and group E treated with combination of benzalkonium bromide eye drops and citalopram suspension.After 2 weeks,OCTA was applied for corneal subarea,followed by measurement of the thickness of corneal epithelium and full-thickness of the cornea of all mice,and then the mean values were calculated.Results The thickness of corneal epithelium and fullthickness of the cornea was (66 ±7) μm and (141 ± 11) μm in the group A,(66 ± 8) μm and (140 ± 12) μm in the group B and D,(73 ± 10) μm and (141 ± 14) μm in the group C,(76 ± 12) μm and (141 ± 15) μm in the E group,respectively.And there was no significant difference in the thickness of corneal epithelium and full-thickness of the cornea before treatment and 2 weeks after treatment in the group A,B and D (all P ＞ 0.05),but both variables were markedly thickened in group C and E 2 weeks after treatment,and the difference was statistically significant (all P ＜0.05).Moreover,the increased levels on the both variables in the group E was higher than those in the group C 2 weeks after treatment,and the difference was statistically significant (both P ＜ 0.05).The average thickness of corneal epithelium and full-thickness of the cornea in the group C and E were significantly thickened after treatment,and the difference was statistically significant (all P ＜ 0.05).The average values of both variables in the group C and E were obviously larger than those in the group A,and the difference was statistically significant (all P ＜ 0.05).Conclusion Citalopram alone has no significant effects on the corneal thickness by OCTA,whereas both the thickness of corneal epithelium and fullthickness of the cornea tend to thicken by benzalkonium bromide treatment,which has a synergistic effect on corneal thickening with citalopram.

Comparative study of citalopram in treatment of behavioral and psychological symptoms of dementia and cognitive function in Alzheimer's disease patients / 中华行为医学与脑科学杂志

Objective To observe the efficacy and safety of citalopram in the treatment of behav-ioural and psychological symptoms of dementia(BPSD)and cognitive function of Alzheimer's disease(AD) patients.Methods From April 2015 to February 2016,80 cases of moderate Alzheimer's disease(according to the clinical dementia rating scale,CDR)with symptoms of BPSD in Qingdao Mental Health Center were collected and randomly divided into treatment group and control group.Treatment group was given citalopram (10 to 30 mg/d),the control group was given the same dose of placebo,and the patients in both group were given memantine(10 mg/bid)for 12 weeks.Simple mental state examination(MMSE)was used to measure cognitive function.Neural psychiatric questionnaire(NPI)measurement was used to evaluate BPSD and the TESS was used to assess adverse effects.Results Decreased scores of MMSE between the treatment group and the control group were respectively(0.67±0.77)and(0.26±0.68)after 12 weeks of treatment.There was significant difference in decreased scores of MMSE between the two groups(t=2.49,P=0.02).The scores of NPI in agitation/attack(t=2.986,P=0.04),apathy(t=3.144,P=0.002),indifference/dysthymia (t=6.094,P=0.000)and anxiety(t=6.496,P=0.000)showed statistically significant differences between the two groups.There were no significant difference in TESS scores(P>0.05).The most frequently adverse e-vents in the study included dizziness,headache,fatigue and nausea.QTc interval prolongation were found in participants treated with 30 mg citalopram per day in the study group.Conclusion Citalopram is an effec-tive and safe drug in the treatment of BPSD and cognitive function associated with moderate AD.

Serum N-Desmethylcitalopram Concentrations are Associated with the Clinical Response to Citalopram of Patients with Major Depression

OBJECTIVE: Citalopram (CITA) is a widely used and well-tolerated selective serotonin reuptake inhibitor. The aim of the study was to evaluate the possible influences of serum concentrations of CITA and its major metabolite n-desmethylcitalopram (NDCITA) on the efficacy and tolerability of CITA in patients with major depressive disorder. METHODS: The study included 46 outpatients with major depressive disorder who received CITA. The efficacy and tolerability were assessed for 6 weeks. Serum CITA and NDCITA levels were measured at the 4th week. RESULTS: The HDRS17 total scores of the patients with high NDCITA and CITA & NDCITA concentrations showed a more significant reduction compared to the patients with expected and low serum NDCITA and CITA & NDCITA concentrations. However, we did not observe a correlation between the serum concentrations and the side effects of CITA, NDCITA, and CITA & NDCITA. CONCLUSION: Our results suggested the potential contribution of NDCITA to the antidepressant effect of CITA. Further studies involving larger clinical samples are required to confirm the impact of serum NDCITA concentrations on the efficacy of CITA.

Síndrome de abstinencia neonatal debido a exposición prenatal al citalopram: a propósito de un caso / Neonatal abstinence syndrome due to prenatally citalopram exposure: A case report

El síndrome de abstinencia neonatal (SAN) debido a la exposición prenatal al citalopram se desarrolla durante los primeros días de vida, incluso con una exposición al fármaco en dosis bajas. El tratamiento de apoyo es la primera opción, aunque puede usarse el fenobarbital en el tratamiento de este síndrome. No debe interrumpirse la lactancia. Debe hacerse un seguimiento de estos recién nacidos para establecer el desenlace del SAN y las consecuencias en el desarrollo neurológico. En este artículo presentamos el caso de un recién nacido con SAN debido a exposición al citalopram en una dosis más baja que lo informado previamente en la bibliografía durante los últimos seis meses del embarazo. Se utilizó el fenobarbital debido al fracaso del tratamiento no farmacológico.

Neonatal abstinence syndrome (NAS) due to prenatally exposure to citalopram can develop during the first days of life even with low dose of drug exposure. Supportive management is the first choice but phenobarbital can be used in treatment of this syndrome. Breastfeeding should not be interrupted. These neonates should be followed both for NAS and neurodevelopmental outcome. In this article, we reported a newborn with NAS due to citalopram exposure with a lower dose than previously reported in the literature, during the last six months of pregnancy. Phenobarbital was used because of non-pharmacological treatment failure.

Association of citalopram with congenital anomalies: A meta-analysis

OBJECTIVE: The antenatal use of citalopram, a widely prescribed selective serotonin reuptake inhibitor, has been suspected to be associated with congenital, particularly cardiac, anomalies. This study aimed to prove the association between citalopram use and congenital anomalies. METHODS: We searched the English literature from July 1998 to July 2015, by using the search terms ‘ citalopram’, ‘ pregnancy’, ‘ birth defects’, ‘ congenital anomalies’, and ‘ malformations’ in PubMed, Embase, Web of Science, and the Cochrane Library. RESULTS: Eight eligible articles were analyzed including a total of 1,507,896 participants. The odds ratio (OR) of major malformations associated with citalopram use during pregnancy was 1.07 (95% confidence interval [CI], 0.98 to 1.17). Concerning cardiac malformations, the OR for all included studies was 1.31 (95% CI, 0.88 to 1.93). The analysis of cardiac malformations was repeated to reduce heterogeneity after excluding one outlier study (OR, 1.03; 95% CI, 0.84 to 1.26). CONCLUSION: From our data, it can be concluded that citalopram use is not associated with major birth defects. However, physicians should carefully weigh the benefits against the potential risks of citalopram use, and counsel patients accordingly.

Clinical Observation of Mirtazapine Combined with Citalopram in the Treatment of Sleep Disorder of De-pressive Patients / 中国药房

OBJECTIVE:To investigate the clinical efficacy and safety of mirtazapine combined with citalopram in the treat-ment of sleep disorder in depressive patients. METHODS:One hundred and sixty-five depressive patients with sleep disorder were selected and divided into control group (82 cases) and treatment group (83 cases) according to random number table. Control group took Escitalopram oxalate tablet 10 mg,once every night,increasing to 20 mg according to disease condition;treatment group was additionally given Mirtazapine tablet 15 mg,once every night,increasing to 30 mg one week later. Both groups re-ceived treatment for consecutive 6 months. HAMD-17 and MADRS were observed in 2 groups before and after treatment,and the sleep quality of 2 groups were evaluated by PSQI before and after treatment;the sleep structure was measured by using polysom-nography before and after treatment;clinical efficacies and the occurrence of ADR were compared between 2 groups. RESULTS:Before treatment,there was no statistical significance in HAMD-17,MADRS and PSQI score,sleep structure between 2 groups (P>0.05);after treatment,above scores and indexes of 2 groups were all improved significantly,and the treatment group was sig-nificantly better than the control group,with statistical significance(P0.05). CONCLUSIONS:Citalopram combined with mirtazapine shows sig-nificant therapeutic efficacy for sleep disorder of depressive patients,and can significantly improve sleep structure,adjust sleep cy-cle and improve sleep quality with good safety.

Comparing the Effects of Bupropion and Escitalopram on Excessive Internet Game Play in Patients with Major Depressive Disorder

OBJECTIVE: Several studies have suggested the efficacy of bupropion and escitalopram on reducing the excessive internet game play. We hypothesized that both bupropion and escitalopram would be effective on reducing the severity of depressive symptoms and internet gaming disorder (IGD) symptoms in patients with both major depressive disorder and IGD. However, the changes in brain connectivity between the default mode network (DMN) and the salience network were different between bupropion and escitalopram due to their different pharmacodynamics. METHODS: This study was designed as a 12-week double blind prospective trial. Thirty patients were recruited for this research (15 bupropion group+15 escitalopram group). To assess the differential functional connectivity (FC) between the hubs of the DMN and the salience network, we selected 12 regions from the automated anatomical labeling in PickAtals software. RESULTS: After drug treatment, the depressive symptoms and IGD symptoms in both groups were improved. Impulsivity and attentional symptoms in the bupropion group were significantly decreased, compared to the escitalopram group. After treatment, FC within only the DMN in escitalopram decreased while FC between DMN and salience network in bupropion group decreased. Bupropion was associated with significantly decreased FC within the salience network and between the salience network and the DMN, compared to escitalopram. CONCLUSION: Bupropion showed greater effects than escitalopram on reducing impulsivity and attentional symptoms. Decreased brain connectivity between the salience network and the DMN appears to be associated with improved excessive IGD symptoms and impulsivity in MDD patients with IGD.