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.

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.

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).

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.

Value of Chuanjin Qinggan decoction in improving the depressive state of patients with herpes zoster combined with depression

BACKGROUND Western medicine is beneficial for the recovery of neurological function in patients with depression,but some patients experience side effects such as headaches,dizziness,nausea,gastrointestinal symptoms,insomnia,and cardiac dysfunction.In recent years,integrative medicine has achieved positive results in the treatment of various diseases.AIM To study Chuanjin Qinggan decoction combined with selective serotonin reuptake inhibitors(SSRIs)in patients with herpes zoster complicated by depression.METHODS Patients with herpes zoster complicated by depression who were treated at the Yantai Hospital of Traditional Chinese Medicine from January 2021 to December 2022 were retrospectively selected as research participants.Among them,43 patients with herpes zoster complicated by depression who received SSRI treatment between January and December 2021 were assigned to the Western medicine group,while those who received combined treatment of traditional Chinese and Western medicine between January and December 2022 were assigned to the combined group.Both groups were treated for eight weeks.The degree of pain,effect of herpes zoster treatment,degree of improvement in depressive symptoms,serum neurotransmitter levels,sleep quality,and occurrence of adverse reactions were compared between the two groups.RESULTS We found that after eight weeks of drug treatment,the two treatment schemes achieved differing efficacy.In further comparison,we found that,compared with patients treated with SSRIs alone,patients treated with Chuanjin Qinggan decoction combined with SSRIs showed more significant improvement in depression and a greater increase in dopamine and 5-hydroxytryptamine levels after treatment(P<0.05).Patients treated with Chuanjin Qinggan decoction combined with SSRIs also experienced lower pain,better treatment efficacy for herpes zoster,better sleep quality,and a lower incidence of adverse reactions compared to those treated with SSRIs alone(P<0.05).All minor adverse reactions occurring during treatment were resolved after symptomatic treatment.CONCLUSION The treatment scheme of Chuanjin Qinggan decoction combined with SSRIs can improve the psychological state of patients with herpes zoster complicated by depression and alleviate adverse reactions.

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.

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.

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.

Prevalence, clinical features and treatment of depression in Parkinson's disease: An update

Parkinson's disease(PD) is one of the most prevalent neurodegenerative diseases which typically affects individuals over 65 years. Although the symptomatology is predominantly motor, neuropsychiatric manifestations, e.g., depression, apathy, anxiety, and cognitive impairment occur in the course of the illness and can have a great impact on the quality of life in these patients. Parkinson's disease is commonly comorbid with depression with prevalence rates of depression, generally higher than those reported in general population. Depression in PD is frequently underestimated andconsequently undertreated, which have significant effects on the quality of life in these patients. The neurobiology of depression in PD is complex and involves alterations in dopaminergic, serotonergic, noradrenergic and possibly other neurotransmitter systems which are affected in the course of the disease. The tricyclic antidepressants and the selective serotonin reuptake inhibitors are the two classes of antidepressant drugs used for depressive symptoms in PD. Several published studies suggested that both classes are of comparable efficacy. Other serotonergic antidepressants, e.g., nefazodone and trazodone have also been of benefit. Meanwhile, there are limited data available on other drugs but these suggest a benefit from the serotonin and noradrenaline reuptake inhibitors such as mirtazapine, venlafaxine, atomoxetine and duloxetine. Some of the drugs used in symptomatic treatment of PD, e.g., the irreversible selective inhibitors of the enzyme monoamine oxidase-B, rasagiline and selegiline as well as the dopamine receptor agonist pramipexole are likely to have direct antidepressant activity independent of their motor improving action. This would make these drugs an attractive option in depressed subjects with PD. The aim of this review is to provide an updated data on the prevalence, clinical features of depression in subjects with PD. The effects of antiparkinsonian and antidepressant drugs on depressive symptoms in these patients are also discussed.

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.

A functional study of SERT coding variants

Aim To characterize the SSRIs sensitivity in C57 and DBA mouse strain and identify the protein struc- tural determinants that contribute to the SSRIs sensitivity. Methods Multiple behavioral assays were conducted to characterize the SSRIs sensitivity in C57 and DBA mouse strain . We performed in vitro binding and uptake assays to assess the pharmacological properties differences of the SSRIs in C57 and DBA mouse strain. Results The ma- jor difference between the 5-HT transport kinetics of the SERTs was found in their maximal transport capacity rather than the transporter＇ s apparent affinity for 5-HT in two mouse strains. C57 mice displayed a significant loss in cita- lopram sensitivity. DBA mice displayed a significant loss in fluoxetine sensitivity. Paroxetine and YL-0919 displayed the same sensitivity in tow mouse strain. Conclusion Results suggest that the two mouse strain have different re- sponses activity to the treatment of SSRIs. The Kd values for 5-HT transporter binding were significantly different a- mong the five compounds of SSRIs we studied in C57 and DBA mouse strain as well as reuptake assays.

Depressive disorders in patients with epilepsy: Why should neurologists care?

Epilepsy is a complex disorder that is commonly associated with brain dysfunction, social isolation, and vocational difficulty. Each of these factors may contribute to the increased prevalence of psychiatric illness in epilepsy, but emerging evidence is providing a more complete and clearer elucidation of the problem. Clinical investigations have consistently demonstrated that depression has a large impact on subjective health status. In patients with recurrent seizures, depression appears to have a stronger association with quality of life than does the seizure rate. In fact, depression is second only to medication toxicity as the clinical factor that explains the greatest variance in quality of life. Only a small number of studies have investigated the plausible neurobiological mechanisms of depression in epilepsy, but preliminary data suggest that underlying brain dysfunction may be a more important predictor than vocational or social disability. Furthermore, specific aspects of hippocampal dysfunction may be a causal factor in the genesis and maintenance of depression in temporal lobe epilepsy. Current treatment recommendations for depression in epilepsy are similar to those for otherwise neurologically normal depressed patients, emphasizing the role of serotonin reuptake inhibitors, but certain antidepressants should be used with caution. Ongoing studies are attempting to define optimal treatment strategies, and more definitive data to guide clinical management are expected to become available in the near future.

Comparison of Age and Gender Differences of Tryptophan Metabolites in Patients of Major Monopolar and Bipolar Depression

Background: No research has been done for the determination of plasma levels of tryptophan metabolites in patients of monopolar and bipolar depression. 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: No significant age and gender differences were shown in monopolar depressive patients and some differences were shown in bipolar patients. The administration of drugs such as antidepressants, antipsychotics, mood stabilizers do not seem to have affected the results. Conclusion: In patients of major monopolar depression age and gender differences of plasma levels of tryptophan metabolites disappear although significant differences are observed in healthy volunteers. Some differences of age and gender differences were shown between monopolar and bipolar depressive patients.

Relief of hot flashes with escitalopram in non-depressed menopausal women in Japan: Results of a retrospective analysis

Purpose: Hormone therapy (estrogen with or without progestin) remains the gold standard treatment for hot flashes in menopausal women, but concerns for the risk of hormone therapy have resulted in its decline and a demand for nonhormonal treatments with demonstrated efficacy for hot flashes. Aim of this study was to examine the efficacy of selective serotonin reuptake inhibitor escitalopram on hot flashes in a healthy sample of non-depressant menopausal women in Japan. Methods: We retrospectively analyzed the medical records of 11 menopausal patients with hot flashes, who received escitalopram (10 mg daily) for 2 weeks between March and August 2012. Hot flashes severities and scores were recorded on a scale of 0 to 10 points, at beginning and end of 2 weeks treatment. Results: At 2 weeks of therapy, 9 of 11 patients reported significant decreases in hot flash frequency and severity, but the remission of the symptom was not observed in 2 patients. Speed of relief from hot flashes was rapid (within one week). Conclusions: Escitalopram 10 mg/day may be a prompt and effective option for treating hot flashes in menopausal women who do not want to use hormone replacement therapy.