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.

Selective serotonin reuptake inhibitors and Alzheimer’s disease

Given the failure to develop disease-modifying therapies for Alzheimer’s disease(AD),strategies aiming at preventing or delaying the onset of the disease are being prioritized.While the debate regarding whether depression is an etiological risk factor or a prodrome of AD rages on,a key determining factor may be the timing of depression onset in older adults.There is increasing evidence that untreated early-onset depression is a risk factor and that late-onset depression may be a catalyst of cognitive decline.Data from animal studies have shown a beneficial impact of selective serotonin reuptake inhibitors on pathophysiological biomarkers of AD including amyloid burden,tau deposits and neurogenesis.In humans,studies focusing on subjects with a prior history of depression also showed a delay in the onset of AD in those treated with most selective serotonin reuptake inhibitors.Paroxetine,which has strong anticholinergic properties,was associated with increased mortality and mixed effects on amyloid and tau deposits in mice,as well as increased odds of developing AD in humans.Although most of the data regarding selective serotonin reuptake inhibitors is promising,findings should be interpreted cautiously because of notable methodological heterogeneity between studies.There is thus a need to conduct large scale randomized controlled trials with long follow up periods to clarify the dose-effect relationship of specific serotonergic antidepressants on AD prevention.

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.

Mouse strain differences in selective serotonin reuptake inhibitors sensitivity correlates with serotonin transporter binding and function

OBJECTIVE Selective serotonin reuptake inhibitors(SSRIs) bind 5-HT transporters,leading to the accumulation of 5-HT and amelioration of depression.Although different mouse strain showed different sensitivity to SSRIs in mouse models of depression,the reason for these strain differences remains unclear.Here,therefore,in the present study,we examined immobility time and locomotor activity in two mouse strains,namely,C57BL/6 J and DBA/2 J mice,and the effects of the SSRIs fluoxetine.Furthermore,we analyzed 5-HT transporter binding and reuptake inhibition in both strains to explore their relationship with the immobility and locomotor activity effects of the three SSRIs in these two mouse strains.METHODS Strain differences in SSRI effects in the tail suspension test(TST) and forced swimming test(FST).To initiate our studies,we sought to confirm that SERT strain variation did not alter SERT protein expression,5-HT recognition,or uptake activity when expressed in C57BL/6 J and DBA/2 J mice.Radioligand binding assays were conducted to determine the affinity of the SSRIs for the 5-HT transporters in the two mouse strains.RESULTS SSRI citalopram dose-dependently reduced immobility time in both the FST and TST in DBA/2 J but not C57BL/6 J mouse strains,whereas fluoxetine showed opposite results.Paroxetine reduced immobility time similarly in both strains.The affinity of citalopram for the 5-HT transporter in DBA/2 J mice was 700-fold higher than that for in C57BL/6 J mice,whereas the affinity of fluoxetine in C57BL/6 J mice was 100-fold higher than that in the DBA/2 J mouse.Furthermore,High citalopram concentrations were required to [3 H]5-HT uptake in C57BL/6 J but not DBA/2 J mouse cortical synaptosomes,whereas fluoxetine also showed opposite results.CONCLUSION Immobility duration depends on 5-HT transporter binding levels,leading to apparent strain differences in immobility time in FST and TST.Furthermore,differences in 5-HT transporter binding may cause variations in SSRI responses on behaviors.SERT mutation mice maintained sensitivity to paroxetine,an antidepressant that is unaffected by the mouse mutation.Therefore,the background strain of these mice likely contributes to the acute behavioral actions of SSRIs in immobility time.These differences may help to explain some of the discrepancies in studies that used these strains of mice to examine the role of 5-HT in mouse models of depression.Future studies should investigate additional neural substrates and molecular mechanisms underlying strain variations in mouse models of depression to help identify genetic predispositions to this disorder in humans.

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.

The Selective Serotonin Reuptake Inhibitor-Sertraline Diminishes Conspecific Aggression in Male Fighting <i>Betta splendens</i>Fish

In conspecific type of aggression the modulation of 5-hydroxytryptamine (5-HT) plays a main role. A decrease of 5-HT in the brain intensifies this type of aggression and in contrast, the increase of 5-HT reduces it. The aim of this study was to examine the effects of different concentrations of sertraline HCl on aggressive behavior of Betta splendens male fish. It was concluded that sertraline added to aquarium water in the dose of 0.4, 4.0 and/or 100.0 μg·L-1 BW during 14 days of exposition increased synaptic levels of 5-HT which in turn resulted in reduction of specific aggressive behavior in the environmental concentrations (0.4 μg) and then times higher. Sertraline caused a periodic, and sometimes even total weakening of the male-male type fight, which was a standard trial applied in ethological research on the Siamese fighting fish. In the current study, the most effective one is proved to be the dose of 4.0 μg·L-1 BW (parallel to earlier investigated fluoxetine in the same dose).

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.

Selective serotonin reuptake inhibitors in the treatment of premature ejaculation

Objective To review and assess the update studies regarding selective serotonin reuptake inhibitors （SSRIs） in the treatment of premature ejaculation （PE） and then provide practical recommendations and possible mechanisms concerning state of the art knowledge for the use of SSRIs in alleviating PE. Data sources Using the Medline, 48 articles published from January 1st, 1996 to August 1st, 2006 concerning the use of SSRIs and their possible mechanisms in alleviating PE were found and reviewed. Study selection PE, rapid ejaculation, early ejaculation and SSRIs were employed as the keywords, and relevant articles about the use of SSRIs and their possible mechanisms in the treatment of PE were selected. Results Many kinds of SSRIs, such as fluoxetine, sertraline, paroxetine and citalopram, have widely been employed to treat PE. However, their effects are moderate and there is no a universal agreement about the kind, dose, protocol and duration. Dapoxetine, as the first prescription treatment of PE, may change this bottle-neck situation. SSRIs are suggested to be used in young men with lifelong PE, and acquired PE when etiological factors are removed but PE still exists. Phosphodiesterase 5 inhibitors （PDE5-ls） are suggested to be employed alone or combined with SSRIs when SSRIs fail to treat PE or sexual dysfunction associated with SSRIs occurs. The protocol of taking drugs on demand based on taking them daily for a suitable period is proposed to be chosen firstly. The possible mechanisms include increasing serotonergic neurotransmission and activating 5-hydroxytryptamine 2C （5-HT2c） receptors, then switching the ejaculatory threshold to a higher level, decreasing the penile sensitivity and their own effect of antidepression. Conclusion The efficacies of the current SSRIs are moderate in the treatment of PE and they have not been approved by the FDA, therefore new SSRI like dapoxetine needs to be further evaluated.

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.

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.

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).

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.

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.

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.

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.

Platelets and depression in cardiovascular disease:A brief review of the current literature

Major depression is an independent risk factor for cardiovascular mortality and morbidity. The exact mechanisms linking depression and increased cardiovascular risk remain poorly understood. Several mechanisms have been proposed including increased platelet reactivity. This review focuses on the current literature that examines the platelet hypothesis of depression. To date studies show increased serotonin response, increased platelet serotonin receptor density, decreased serotonin transporter binding, and decreased platelet serotonin levels in individuals with depression. However other studies have shown no change in serotonin uptake. In addition to platelet serotonin specific pathways, other platelet pathways that have shown significant changes in depressed individuals include blunting of the platelet adenosine response, increased platelet thrombin response, increased glycoprotein Ⅰb expression, increased P-selectin, β thromboglobulin, and platelet factor four, as well as decreased platelet brain derived neurotrophic factor. However there are other studies that show conflicting evidence of increased platelet activation as measured by integrin receptor α2b β3. Other conflictingdata include α adrenergic density and platelet response to augmented serotonin. The direction of future research in platelet functional changes in depression and coronary artery disease should continue to focus on serotonin specific pathways with emphasis on potential mechanisms of specific pathway changes.

Acupuncture/electroacupuncture enhances antidepressant effect of Seroxat:the Symptom Checklist-90 scores

One hundred and five patients with primary unipolar depression were randomly divided into three groups： drug group （Seroxat administration）, acupuncture group （Seroxat plus acupunc- ture）, and electroacupuncture group （Seroxat plus acupuncture plus electroacupuncture）. Patients＇ symptoms were evaluated using a psychometric questionnaire, the Symptom Check- list-90, before intervention and after 2, 4, 6 and 10 weeks of treatment. The individual factor scores and the total score from the Symptom Checldist-90 reduced in all three groups as treat- ment progressed. In the acupuncture and electroacupuncture groups, the total score and the factor scores for obsessive-compulsive symptoms, depression, and anxiety were significantly lower than those in the drug group. There was no significant difference in the factor scores or total scores between the acupuncture and electroacupuncture groups. Some factor scores in the electroacupuncture group, such as somatization, depression, hostility, and phobic anxiety, were increased at 10 weeks compared with the respective score immediately after the course of electroacupuncture at 6 weeks. Our findings indicate that administration of Seroxat alone or in combination with acupuncture/electroacupuncture can produce a significant effect in patients with primary unipolar depression. Furthermore, acupuncture/electroacupuncture has a rapid onset of therapeutic effect and produces a noticeable improvement in obsessive-compulsive, de- pressive and anxiety symptoms.

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.

Expert consensus of Chinese Association for the Study of Pain on the non-opioid analgesics for chronic musculoskeletal pain

Chronic musculoskeletal pain(CMP)is a common occurrence in clinical practice and there are a variety of options for the treatment of it.However,the pharmacological therapy is still considered to be a primary treatment.The recent years have witnessed the emergence of opioid crisis,yet there are no relevant guidelines on how to treat CMP with non-opioid analgesics properly.The Chinese Medical Association for the Study of Pain convened a panel meeting to develop clinical practice consensus for the treatment of CMP with non-opioid analgesics.The purpose of this consensus is to present the application of nonsteroidal antiinflammatory drugs,serotonin norepinephrine reuptake inhibitors,serotonin and norepinephrine reuptake inhibitors,muscle relaxants,ion channel drugs and topical drugs in CMP.