Comparison of paroxetine and dapoxetine, a novel selective serotonin reuptake inhibitor in the treatment of premature ejaculation

Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation （PE）, Our objective in this study was to characterize the efficacy of on-demand dapoxetine （30 and 60 mg） and daily paroxetine （20 mg） usage in treating PE, We conducted a 1 month study involving a total of 150 patients. Patients were divided into three groups of 50, Group 1 were treated with on-demand dapoxetine （30 mg）, Group 2 with on-demand dapoxetine （60 mg） and Group 3 with daily paroxetine （20 rag）, Our outcome measurement was increased from baseline intravaginal ejaculatory latency time （IELT） after treatment, The IELT increased from baseline to posttreatment by 117%, 117% and 170% in the paroxetine group （P 〈 0,01）, 30 mg dapoxetine group （P 〈 0,01） and 60 mg dapoxetine group （P 〈 0.01）, respectively, The increase from baseline IELT were similar for the 30 mg dapoxetine and paroxetine groups （P 〉 0,05）, while the 60 mg dapoxetine group had a larger posttreatment IELT increase compared with the 30 mg dapoxetine （P〈 0.05） and paroxetine （P〈 0.01） groups, Dapoxetine （60 mg） 1-3 h before planned intercourse is a very effective treatment modality for PE. However, an on-demand dose of 30 mg dapoxetine is no more effective than the currently prescribed paroxetine treatment.

Relationship between use of selective serotonin reuptake inhibitors and irritable bowel syndrome: A populationbased cohort study

AIM To investigate the relationship between selective serotonin reuptake inhibitor(SSRI)use and the subsequent development of irritable bowel syndrome(IBS).METHODS This retrospective,observational,population-based cohort study collected data from Taiwan’s National Health Insurance Research Database.A total of 19653patients newly using SSRIs and 78612 patients not using SSRIs,matched by age and sex at a ratio of 1:4, were enrolled in the study from January 1,2000 to December 31,2010.The patients were followed until IBS diagnosis,withdrawal from the National Health Insurance system,or the end of 2011.We analyzed the effects of SSRIs on the risk of subsequent IBS using Cox proportional hazards regression models.RESULTS A total of 236 patients in the SSRI cohort(incidence,2.17/1000 person-years)and 478 patients in the comparison cohort(incidence,1.04/1000 person-years)received a new diagnosis of IBS.The mean follow-up period from SSRI exposure to IBS diagnosis was 2.05years.The incidence of IBS increased with advancing age.Patients with anxiety disorders had a significantly increased adjusted hazard ratio(a HR)of IBS(a HR=1.33,95%CI:1.11-1.59,P=0.002).After adjusting for sex,age,urbanization,family income,area of residence,occupation,the use of anti-psychotics and other comorbidities,the overall a HR in the SSRI cohort compared with that in the comparison cohort was1.74(95%CI:1.44-2.10;P<0.001).The cumulative incidence of IBS was higher in the SSRI cohort than in the non-SSRI cohort(log-rank test,P<0.001).CONCLUSION SSRI users show an increased risk of subsequent diagnosis of IBS in Taiwan.

Fluoxetine,a selective serotonin reuptake inhibitor used clinically,improves bladder function in a mouse model of moderate spinal cord injury

After spinal cord injury,the upward conduction of the spinal cord is lost,resulting in the loss of micturition control,which manifests as detrusor sphincter dyssynergia and insufficient micturition.Studies have shown that serotonergic axons play important roles in the control of the descending urination tract.In this study,mouse models of moderate spinal cord contusions were established.The serotonin agonists quipazine(0.2 mg/kg),8-hydroxy-2-(di-n-propylamino)tetralin(8-OH-DAPT,0.1 mg/kg),buspirone(1 mg/kg),sumatriptan(1 mg/kg),and rizatriptan(50 mg/kg),the serotonin reuptake inhibitors fluoxetine(20 mg/kg)and duloxetine(1 mg/kg),and the dopamine receptor agonist SKF-82197(0.1 mg/kg)were intraperitoneally administered to the model mice 35 days post-injury in an acute manner.The voided stain on paper method and urodynamics revealed that fluoxetine reduced the amount of residual urine in the bladder and decreased bladder and external urethral sphincter pressure in a mouse model of moderate spinal cord injury.However,fluoxetine did not improve the micturition function in a mouse model of severe spinal cord injury.In contrast,the other serotonergic drugs had no effects on the micturition functions of spinal cord injury model mice.This study was ethically approved by the Institutional Animal Care and Use Committee of Jiangsu Province Hospital of Chinese Medicine(approval No.2020DW-20-02)on September 11,2020.

Does serotonin reuptake inhibitor therapy increase the risk of post-sphincterotomy bleeding in patients undergoing endoscopic retrograde cholangio-pancreatography?

To evaluate the risk of immediate and delayed bleeding following sphincterotomy procedure. METHODSThis retrospective cohort study was conducted with all patients who underwent endoscopic sphincterotomy during January 2006 to September 2015 at a tertiary academic center. Patients were grouped according to pre procedural usage of serotonin reuptake inhibitors (SRIs). Both groups were matched for demographic and clinical characteristics. Patients with thrombocytopenia, increased international normalized ratio, or a history of bleeding or coagulation disorders, concurrent use of other antiplatelet/anticoagulants were excluded from the study. RESULTSA total of 447 patients were included, of which 219 (45.9%) used SRIs and 228 (54.1%) cases did not. There was no significant difference in acute or delayed bleeding during endoscopic sphincterotomy between the two groups. (8.2% vs 12.3%, P = 0.16). CONCLUSIONThe use of SRIs was not associated with an increased risk of post-sphincterotomy bleeding. To our best knowledge, this is the first study to explore this association.

Serotonin syndrome controversies:A need for consensus

Serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it is still an enigma in terms of terminology,clinical features,etiology,pathophysiology,diagnostic criteria,and therapeutic measures.The majority of SS cases have previously been reported by toxicology or psychiatry centers,particularly in people with mental illness.However,serotonergic medications are used for a variety of conditions other than mental illness.Serotonergic properties have been discovered in several new drugs,including over-the-counter medications.These days,cases are reported in non-toxicology centers,such as perioperative settings,neurology clinics,cardiology settings,gynecology settings,and pediatric clinics.Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers.Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings.Patients may develop SS at therapeutic dosages.Moreover,these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons.Thus,the clinical presentation(onset,severity,and clinical features)in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings.They produce considerable diversity in many aspects of SS.However,other experts discount these new developments in SS.Since SS is a potentially lethal illness,consensus is required on several concerns related to SS.

The role of selective serotonin reuptake inhibitors and tricyclic antidepressants in addressing reduction of Meniere's disease burden:A scoping review

Objective:To assess the effect of selective serotonin reuptake inhibitors(SSRIs)and tricyclic antidepressants(TCAs)in reducing vertigo,tinnitus,and hearing loss among patients with Meniere's disease(MD).Data Sources:The following databases were utilized in this scoping review:Ovid Medline,PubMed-NCBI,CINAHL,Cochrane Library,Web of Science,and Clinicaltrials.gov.Method:Studies were identified through the following search phrases:"serotonin specific reuptake inhibitors"OR"tricyclic antidepressants"AND"Meniere's disease."References from included manuscripts were examined for possible inclusion of additional studies.Results:The literature search yielded 23 results,which were screened by three independent reviewers.Seventeen studies and three duplicates were excluded.An examination of references from the included studies yielded two additional publications.A total of four published studies assessing SSRIs and TCAs among 147 patients with MD were ultimately included.Four studies described significant reductions in vertigo attack frequency among patients treated with either SSRIs or TCAs compared to their pretreatment baseline.Three studies assessed the drugs'effects on hearing,of which none found a significant difference among patients treated with SSRIs or TCAs.One study found a significant decrease in patient-reported tinnitus following treatment with TCAs or SSRIs compared to their pretreatment baseline.Conclusions:Data exploring SSRIs and TCAs among patients with MD suggests that these medications may reduce the frequency of tinnitus and vertigo,although there was significant heterogeneity in outcome reporting.There remains a need for larger-scale prospective studies that emphasize objective data to evaluate their effective-ness in reducing common MD symptoms.

Possible association of the 5-HTTLPR serotonin transporter promoter gene polymorphism with premature ejaculation in a Turkish population

We evaluated the genotypes of the serotonin transporter gene （5-HTT） in patients with premature ejaculation （PE） to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene （5-HTTLPR） were determined. The 5-HTTLPR （serotonin transporter promoter gene） genotypes in PE patients vs. controls were distributed as follows： L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene： LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the Z-test. The short （S） allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls （P 〈 0.05）. We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup （such as primary and secondary PE） responses to selective serotonin reuptake inhibitors as well as ethnic differences.

Differences of Plasma Levels of Tryptophan, Serotonin, 5-Hydroxyindole Acetic Acid, and Kynurenine between Healthy People and Patients of Major Monopolar Depression at Various Age and Gender

Background: It is not well analyzed whether there are differences in plasma levels of tryptophan (TRP) metabolites between healthy control people (HC) and patients of major monopolar depression (MMD). Methods: Ultra high-speed liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive patients. Results: There are no significant differences between plasma levels of TRP between HC and MMD. Plasma levels of TRP of HC are higher in young men, young women, old men, and old women in this order. Serotonin (5-HT) levels are higher in MMD than HC. Plasma levels of 5-HIAA of HC are also higher than those of patients of MMD. Plasma levels of kynurenine (KYN) of healthy old men and old women are higher than those of young men and old women. Plasma levels of KYN are higher in old women and young men of MMD than those of HC. Conclusion: Plasma levels of 5-HT are higher in patients of MMD than those of HC, which may suggest that use of drugs inhibiting the 5-HT transportation may increase plasma levels of 5-HT in MMD.

Treatment of functional dyspepsia with sertraline:A double-blind randomized placebo-controlled pilot study

AIM:To evaluate sertraline,a selective serotonin reuptake inhibitor in the treatment of patients with functional dyspepsia.METHODS:Consecutive tertiary hospital patients with a clinical diagnosis of functional dyspepsia(FD) according to the Rome Ⅱ criteria with a Hong Kong dyspepsia index(HKDI) of greater than 16 were recruited.Patients commenced enrolment prior to the inception of the Rome Ⅲ criteria for functional dyspepsia.All patients were ethnic Chinese,had a normal upper endoscopy and were Helicobacter pylori negative prior to enrolment.Study patients were randomized to receive sertraline 50 mg or placebo daily for 8 wk.HKDI symptom scores,quality of life,hospital anxiety and depression(HAD) scale and global symptom relief were evaluated before,during and after treatment.Adverse effects were monitored during and after treatment.RESULTS:A total of 193 patients were randomized in the intention to treat(ITT),and 150 patients were included in the per protocol(PP) analysis.In both the ITT and PP,there was no difference in the primary outcome of global dyspepsia symptoms between the sertraline and placebo groups at week 8.In the ITT analysis,98 and 95 patients were randomized to the sertraline and placebo groups respectively.A total of 43 patients withdrew from the study(22.3%) by week 8,with 23 of the 24 drop-outs in the sertraline group occurring prior to week 4(95.8%).In contrast,in the placebo arm,11 of 19 patients dropped out by week 4(57.9%).Utilizing the last response carried forward to account for the drop-outs,there were no differences between the sertraline and placebo groups at baseline in terms of the HKDI,HKDI 26.08 ± 6.19 vs 26.70 ± 5.89,P = 0.433;and at week 8,HKDI 22.41 ± 6.36 vs 23.25 ± 7.30,P = 0.352 respectively.In the PP analysis,74 and 76 patients were randomized to the sertraline and placebo groups respectively.At baseline,there were no statistically significant differences between the sertraline and placebo groups,HKDI 25.83 ± 6.313 vs 27.19 ± 5.929 respectively,P = 0.233;however by week 8,patients in the sertraline group demonstrated a statistically significant difference in their Hong Kong Dyspepsia Index compared to placebo,HKDI 20.53 ± 6.917 vs 23.34 ± 7.199,P = 0.02,respectively).There was also no statistically significant difference in overall quality of life measures or the HAD scale related to treatment in either the ITT or PP analysis at week 8.CONCLUSION:This pilot study,the first to examine sertraline,a selective serotonin reuptake inhibitor,for the management of FD,did not find that it was superior to placebo.

Molecular mechanism of noradrenaline during the stress-induced major depressive disorder

Chronic stress-induced depression is a common hallmark of many psychiatric disorders with high morbidity rate.Stress-induced dysregulation of noradrenergic system has been implicated in the pathogenesis of depression.Lack of monoamine in the brain has been believed to be the main causative factor behind pathophysiology of major depressive disorder（MDD） and several antidepressants functions by increasing the monoamine level at the synapses in the brain.However,it is undetermined whether the noradrenergic receptor stimulation is critical for the therapeutic effect of antidepressant.Contrary to noradrenergic receptor stimulation,it has been suggested that the desensitization of β-adrenoceptor is involved in the therapeutic effect of antidepressant.In addition,enhanced noradrenaline（NA） release is central response to stress and thought to be a risk factor for the development of MDD.Moreover,fast acting antidepressant suppresses the hyperactivation of noradrenergic neurons in locus coeruleus（LC）.However,it is unclear how they alter the firing activity of LC neurons.These inconsistent reports about antidepressant effect of NA-reuptake inhibitors（NRIs） and enhanced release of NA as a stress response complicate our understanding about the pathophysiology of MDD.In this review,we will discuss the role of NA in pathophysiology of stress and the mechanism of therapeutic effect of NA in MDD.We will also discuss the possible contributions of each subtype of noradrenergic receptors on LC neurons,hypothalamic-pituitary-adrenal axis（HPA-axis） and brain derived neurotrophic factor-induced hippocampal neurogenesis during stress and therapeutic effect of NRIs in MDD.

Current therapeutic strategies for premature ejaculation and future perspectives

Premature ejaculation （PE） is a common sexual disorder in men that is mediated by disturbances in the peripheral and central nervous systems. Although all pharmaceutical treatments for PE are currently used ＇off-label＇, some novel oral agents and some newer methods of drug administration now provide important relief to PE patients. However, the aetiology of this condition has still not been unified, primarily because of the lack of a standard animal model for basic research and the absence of a widely accepted definition and assessment tool for evidence-based clinical studies in patients with PE. In this review, we focus on the current therapeutic strategies and future treatment perspectives for PE.

Delayed atomoxetine or fluoxetine treatment coupled with limited voluntary running promotes motor recovery in mice after ischemic stroke

Currently, there is an unmet need for treatments promoting post-stroke functional recovery.The aim of this study was to evaluate and compare the dose-dependent effect of delayed atomoxetine or fluoxetine therapy(starting on post-stroke day 5), coupled with limited physical exercise(2 hours daily voluntary wheel running;post-stroke days 9 to 42), on motor recovery of adult male mice after photothrombotic stroke.These drugs are selective norepinephrine or serotonin reuptake inhibitors indicated for disorders unrelated to stroke.The predetermined primary end-point for this study was motor function measured in two tasks of spontaneous motor behaviors in grid-walking and cylinder tests.Additionally, we quantified the running distance and speed throughout the study, the number of parvalbumin-positive neurons in the medial agranular cortex and infarct volumes.Both sensorimotor tests revealed that neither limited physical exercise nor a drug treatment alone significantly facilitated motor recovery in mice after stroke.However, combination of physical exercise with either of the drugs promoted restoration of motor function by day 42 post-stroke, with atomoxetine being a more potent drug.This was accompanied by a significant decrease in parvalbumin-positive inhibitory interneurons in the ipsilateral medial agranular cortex of mice with recovering motor function, while infarct volumes were comparable among experimental groups.If further validated in larger studies, our observations suggest that add-on atomoxetine or fluoxetine therapy coupled with limited, structured physical rehabilitation could offer therapeutic modality for stroke survivors who have difficulty to engage in early, high-intensity physiotherapy.Furthermore, in light of the recently completed Assessment o F Fluoxet INe In s Troke recover Y(AFFINITY) and Efficacy o F Fluoxetine-a randomis Ed Controlled Trial in Stroke(EFFECTS) trials, our observations call for newly designed studies where fluoxetine or atomoxetine pharmacotherapy is evaluated in combination with structured physical rehabilitation rather than alone.This study was approved by the Texas Tech University Health Sciences Center Institutional Animal Care and Use Committee(protocol # 16019).

Stroke recovery enhancing therapies:lessons from recent clinical trials

Poststroke recovery processes include restoration or compensation of function,respectively functions initially lost or new functions acquired after an injury.Therapeutic interventions can enhance these processes and/or reduce processes impeding regeneration.Numerous experimental studies suggest great opportunities for such treatments,but the results from recent large clinical trials using neuromodulators such as dopamine and fluoxetine are disappointing.The reasons for this are manifold affecting forward translation of results from animals models into the human situation.This"translational road block"is defined by differences between animals and humans with regard to the genetic and epigenetic background,size and anatomy of the brain,cerebral vascular anatomy,immune system,as well as clinical function and behavior.Backward blockade includes the incompatible adaption of targets and outcomes in clinical trials with regard to prior preclinical findings.For example,the design of clinical recovery trials varies widely and was characterized by the selection of different clinical endpoints,the inclusion a broad spectrum of stroke subtypes and clinical syndromes as well as different time windows for treatment initiation after infarct onset.This review will discuss these aspects based on the results of the recent stroke recovery trials with the goal to contribute to the currently biggest unmet need in stroke research-the development of a recovery enhancing therapy that improves the functional outcome of a chronic stroke patient.

Comparison of Plasma Levels of Tryptophan Metabolites between Healthy People and Patients of Bipolar Depression at Various Age and Gender

Background: It is not well analyzed whether there are differences in plasma levels of tryptophan (TRP) metabolites between healthy control people (HC) and patients of type II bipolar depression (BDII). Methods: Ultra high-speed liquid chromatography/mass spectrometry has been used for the simultaneous determination of plasma levels of tryptophan metabolites in depressive patients. Results: Plasma levels of TRP are not different between HC and patients of BDII. Serotonin (5-HT) levels are higher in BDII than HC. Plasma levels of 5-HIAA of HC are higher than those of old women of BDII, but lower in young women of BDII. Plasma levels of kynurenine (KYN) of HC are not different from those of patients of BDII. Conclusion: Plasma levels of 5-HT are higher in patients of BDII than those of HC, which may suggest that use of drugs inhibiting the 5-HT transportation and lower transporter biding may increase plasma levels of 5-HT in patients of BD.

Phenomenology of obsessive-compulsive disorder in children and adolescents: Sample from a tertiary care center in Istanbul, Turkey

BACKGROUND Obsessive-compulsive disorder(OCD)is a heterogeneous disease in many respects and exhibits this diversity in terms of phenomenology.It also displays several different characteristics in children compared to adults.AIM To describe the socio-demographic and phenomenological features of children with OCD and to investigate the impact of these features on response to pharmacotherapy.METHODS This retrospective study was carried out with 150 children and adolescents who had been diagnosed with OCD between 2014 and 2018.Data was collected by examining the files of the patients with diagnosis of OCD and similar disorders from the hospital database.Yale-Brown Obsessive-Compulsive Scale for Children was used for the assessment of obsession-compulsion subtypes.The Clinical Global Impression(CGI)scale was used to evaluate the severity of the disease(CGI-S)and global improvement(CGI-I).The predictors of treatment response were evaluated using linear regression analysis.The level of significance for all statistic tests was set as P<0.05.RESULTS The sample was divided into prepubertal(44%)and adolescent(56%)age groups.The most prevalent obsessions were contamination and aggression obsessions,and the most frequent compulsions were washing and checking.While contamination was observed more commonly in the prepubertal age group,the religious obsession was seen more frequently in adolescents.Patients with aggression obsession presented a higher frequency of comorbid anxiety(P=0.022)and mood subgroups(P>0.05).A lower CGI-I score was linked to a lower CGI-S score(95%confidence interval 0.21-0.39,P<0.001)and the prepubertal age of admission(95%confidence interval 0.03-0.87,P=0.020).CONCLUSION The phenomenology of OCD shows differences depending on the age group and the comorbid psychiatric disorders.Earlier identification and treatment of OCD may help to prevent the impairment of the mental health of children and adolescents.

Antidepressant Drugs Modulate Differentially Anti-inflammatory Lithium＇s Property： An in Vitro and in Vivo Study

Li （lithium）, a mood stabilizer has anti-inflammatory effect. However, in clinical practice, Li can be administered together with other antidepressants drugs, such as FLX （fluoxetine）, IMI （imipramine）, NOR （nortriptyline） and ESC （escitalopram）. As interaction between Li and these antidepressant drugs on inflammatory modulation has not been investigated yet, we performed an in vitro protocol using a non-human macrophage cell line. Oxidative and inflammatory markers, as well as cell cycle analysis and cytokine gene expressions were compared among treatments. An IR （inflammatory ratio） was calculated based on the following oxidative-inflammatory variables： nitric oxide, superoxide anion, reactive oxygen molecules, cytokines IL-113, IL-6, TNF-ct and IL-10. The in vitro calculated IR data were validated through an in vivo analysis of 154 human subjects with similar IR. Li and control cells presented similar IR values. FLX, NOR and IMI increased slightly IR values indicating some proinflammatory effect, whereas ESC decreased IR values indicating some anti-inflammatory effect. However, cells exposed to Li ＋ ESC triggered a proinflammatory response on macrophages. Thus, IR comparison results suggest that the Li anti-inflammatory effect is not universal and could be influenced by both basal macrophage-inflammatory state and interaction of other psychiatric drugs. These results could be useful to understand some inconsistencies observed in human studies involving Li and other psychiatric drugs.

Single Exposure to Antidepressants during Infancy Is Associated with Delayed Behavioral Changes in C57BL/6 Mice

As serotoninergic transmission plays a crucial role in higher brain function in mammals, the disturbance of this system will likely have significant effects on emotion and cognition. Previous studies have reported that chronic treatment with Specific Serotonin Reuptake Inhibitors (SSRIs) during both late pregnancy and lactation was associated with abnormal behavior in adult rats. These data imply that disturbances in serotoninergic transmission during neurodevelopment may have negative effects on both the structure and function of the resultant adult brain. Therefore, the effect of a single exposure to an SSRI or a tricyclic antidepressant that preferentially inhibits serotonin reuptake during the pre-weaning period was examined in adult mice. An oral infusion of paroxetine (70 mg/kg), fluvoxamine (250 mg/kg), clomipramine (180 mg/kg), or saline was administered on postnatal day 14. Starting at 11 weeks of age, mice were assessed using a comprehensive behavioral test battery. Mice treated with paroxetine demonstrated altered behavior on the open field and hole-board tasks;those treated with fluvoxamine had behavioral changes on the light-dark box, hole-board, and sucrose preference tasks, while alteration in forced swimming and cued fear behavior were noted in mice treated with clomipramine. These results suggest that even a single administration of an antidepressant could have profound effects on behavior in adulthood, although the effects might differ dependent on the specific drug that was administered.

5-Hydroxytryptamine Changes under Different Pretreatments on Rat Models of Myocardial Infarction and/or Depression

Background：Psychocardiological researches have suggested a central role of 5-hydroxytryptamine （5-HT） on psychocardiological mechanism.This study aimed to further explore the central role of 5-HT and pretreatment effects of XinLingWan on rats with myocardial infarction （M I） and/or depression.Methods：Ninety Sprague-Dawley rats were randomly divided into three groups：MI group,depression group,and MI ＋ depression group （n 30 in each group）.Each group was then divided into three subgroups （n =10 in each subgroup）：a negative control subgroup （NCS）,a Western medicine subgroup （WMS）,and a traditional Chinese medicine subgroup （TCMS）,which were received pretreatment once a day for 4 weeks by saline,20 mg/kg sertraline mixed with 2 ml saline,and 40 mg/kg XingLingWan mixed with 2 ml saline,respectively.Different rat models were established after different pretreatments.Rats were then sacrificed for detection of serum 5-HT,platelet 5-HT,5-HT2.A receptors （5-HT2AR）,and serotonin transporter （SERT）.Data were analyzed by one-way analysis of variance （ANOVA） and least-significant difference （LSD） testing.Results：M I group：compared with NCS,there was a significant increase in WMS and TCMS of serum 5-HT （176.15 ± 11.32 pg/ml vs.334.50 ± 29.09 pg/ml and 474.04 ± 10.86 pg/ml,respectively,both P =0.000）,platelet 5-HT （129.74 ± 27.17 pg/ml vs.322.24 ± 11.60 pg/ml and 340.4 5 ± 17.99 pg/ml,respectively,both P =0.000）;depression group：compared with NCS,there was a significant increase in WMS and TCMS of serum 5-HT （194.69 ± 5.09 pg/ml vs.326.21 ± 39.98 pg/ml and 456.33 ± 23.12 pg/ml,respectively,both P =0.000）,platelet 5-HT （175.15 ± 4.07 pg/ml vs.204.56 ± 18.59 pg/ml and 252.03 ± 22.26 pg/ml,respectively,P =0.004 and P 0.000,respectively）;MI ＋ depression group：compared with NCS,there was a significant increase in both WMS and TCMS of serum 5-HT （182.50 ± 10.23 pg/ml vs.372.55 ± 52.23 pg/ml and 441.76 ± 23.38 pg/ml,respectively,both P =0.000） and platelet 5-HT （180.83 ± 11.08 pg/ml vs.221.12 ± 22.23 pg/ml and 265.37 ± 29.49 pg/ml,respectively,P =0.011 and P =0.000,respectively）.Conclusions：By elevating the amount of 5-HT and modulating 5-HT2AR and SERT levels in serum and platelets,XinLingWan and sertraline were found to exert pretreatment effect on rat models of MI and/or depression.