The relationship between serotonin transporter gene promoter polymorphism and serum lipid levels at young age in a longitudinal population-representative study

The serotonin transporter gene promoter region polymorphism (5-HTTLPR) has been linked to psychiatric disorders, mostly anxiety and affective disorders. In elderly populations 5-HTTLPR polymorphism has also been reported to be associated with serum lipid levels. We have examined the interaction of the 5-HTTLPR polymorphism and the markers of lipid metabolism at young age in a longitudinal, population-representative cohort study. The sample of the Estonian Children Personality Behaviour and Health Study (initially cohorts of 9 and 15 year old children, complete lipid and genotype data for n = 1176) was examined throughout 10 years. Subjects were genotyped and the levels of low-density lipoproteins, high-density lipoproteins, triglycerides, and total cholesterol were measured. Children and adolescents carrying the s allele of the 5-HTTLPR polymorphism had lower levels of low-density lipoprotein and total cholesterol. At the age of 25, the s allele carriers had higher levels of high-density lipoproteins. These associations were independent of gender. Thus the 5-HTTLPR can be associated with the serum lipid levels and in particular low-density lipoproteins already in a young age.     

文拉法辛对选择性5-羟色胺再摄取抑制剂治疗无显效的抑郁症患者的疗效和安全性的临床对照观察

目的探讨抑郁症患者经选择性5-羟色胺再摄取抑制剂（SSRIs）治疗无明显疗效换用文拉法辛治疗后的疗效与安全性。方法将经SSRIs治疗6周以上无显著效果的62例抑郁症患者随机分成2组,一组采用文拉法辛治疗（32例）,另一组继续用SSRIs治疗并且适当增加剂量,治疗观察8周。应用汉密顿抑郁量表（HAMD-17）和不良反应量表（TESS）评定临床疗效及药物不良反应。结果治疗8周末,文拉法辛组治愈率为25.0%（8/32）,SSRIs组治愈率为13.3%（4/30）,两组间比较有显著性差异（P〈0.05）;文拉法辛组与SSRIs组间的TESS评分无显著性差异（1.6±2.4vs.1.7±2.4）。结论抑郁症患者经SSRI治疗无显效时,换用文拉法辛治疗部分患者可获满意疗效且安全性好。     

Comparing SSRI Treatment Costs for Depression Using Retrospective Claims Data: The Role of Nonrandom Selection and Skewed Data

Background and Objectives: Since conventional randomized clinical trials often do not reflect the real world circumstances of prescribing behavior and patient outcomes, the use of retrospective administrative claims databases (RACD) has become more common in treatment cost comparisons among alternative pharmaceutical compounds. Several recent RACD studies have compared treatment costs for depressed patients prescribed SSRIs such as fluoxetine, sertraline and paroxetine. These cost comparisons have reached mixed conclusions. To begin to explain and reconcile the mixed SSRI cost comparison evidence, we undertake a variety of alternative multivariate analyses using a publicly available RACD.
Methods and Data: The 1995 to 1996 data encompasses a time period when all three SSRIs had become well-established agents. We report and compare results from multivariate linear regressions, logistic regressions, ordered probits and sample selectivity models, and examine robustness when adjustments are made for outlier observations and skewed distributions.
Results and Conclusions: While choice of initial SSRI is nonrandom, the effect of sample selectivity on total depression-related and total health care expenditure is neutral across SSRIs. Although most cost measures are numerically greatest for fluoxetine, depression-related outpatient and hospitalization costs do not significantly differ by choice of initial SSRI. These findings are robust to alternative assumptions, specifications, and procedures. Antidepressant medication costs, however, are significantly higher when fluoxetine is the initial SSRI rather than sertraline or paroxetine, reflecting the larger proportion of fluoxetine patients prescribed a daily dosage of two or more capsules. Both total depression-related and total health care log–transformed costs are significantly lower for sertraline than fluoxetine.     

Drug repurposing of selective serotonin reuptake inhibitors: Could these drugs help fight COVID-19 and save lives?

The current 2019 novel coronavirus disease (COVID-19), an emerging infectious disease, is undoubtedly the most challenging pandemic in the 21st century. A total of 92,977,768 confirmed cases of COVID-19 and 1,991,289 deaths were reported globally up to January 14, 2021. COVID-19 also affects people’s mental health and quality of life. At present, there is no effective therapeutic strategy for the management of this disease. Therefore, in the absence of a specific vaccine or curative treatment, it is an urgent need to identify safe, effective and globally available drugs for reducing COVID-19 morbidity and fatalities. In this review, we focus on selective serotonin reuptake inhibitors (SSRIs: a class of antidepressant drugs with widespread availability and an optimal tolerability profile) that can potentially be repurposed for COVID-19 and are currently being tested in clinical trials. We also summarize the existing literature on what is known about the link between serotonin (5-HT) and the immune system. From the evidence reviewed here, we propose fluoxetine as an adjuvant therapeutic agent for COVID-19 based on its known immunomodulatory, anti-inflammatory and antiviral properties. Fluoxetine may potentially reduce pro-inflammatory chemokine/cytokines levels (such as CCL-2, IL-6, and TNF-α) in COVID-19 patients. Furthermore, fluoxetine may help to attenuate neurological complications of COVID-19.     

A naturalistic study in the use of antidepressants in adults with learning disabilities and affective disorders

Very few studies have been undertaken looking at the use of anti-depressants in adults with learning disabilities and, more recently, with the advent of SSRIs there has not been any study comparing the use of SSRIs with tricyclic drugs in this group. A naturalistic study involving adults with learning disabilities suffering from depressive illness was undertaken in Leicestershire that included 104 treatment episodes with tricyclic/tetracyclic groups of drugs and SSRIs and issues related to efficacy, tolerability, side-effects, polypharmacy and discontinuation rates were looked at. The study, despite its limitations, establishes for the first time that depressive illness in patients with learning disabilities does respond to antidepressant treatment in the same way as that of the general population. The findings suggest that SSRIs are better tolerated and present with fewer serious side effects when compared to tricyclic/tetracyclic groups of drugs. The efficacy of both groups of drugs was found to be very similar. This study also highlights that SSRIs are reasonably safe to use in conjunction with drugs like Lithium and Carbamazepine.     

New agents in the treatment of premature ejaculation

Premature ejaculation (PE) is a common male sexual disorder. Recent normative data suggest that men with an intravaginal ejaculatory latency time (IELT) of less than 1 minute have “definite” PE, while men with IELTs between 1 and 1.5 minutes have “probable” PE. Although there is insufficient empirical evidence to identify the etiology of PE, there is limited correlational evidence to suggest that men with PE have high levels of sexual anxiety and inherited altered sensitivity of central 5-HT (serotonin) receptors. Pharmacological modulation of the ejaculatory threshold using off-label daily or on-demand selective serotonin re-uptake inhibitors (SSRIs) offers patients a high likelihood of achieving improved ejaculatory control within a few days of initiating treatment, consequential improvements in sexual desire and other sexual domains and is well tolerated. Investigational drugs such as the ejaculo-selective serotonin transport inhibitors (ESSTIs) such as dapoxetine and UK-390,957 represent a major development in sexual medicine. These drugs offer patients the convenience of on-demand dosing, significant improvements in IELT, ejaculatory control, and sexual satisfaction with minimal adverse effects.     

Melancholia with Onset During Treatment With SRISs

A defined group of medical records was surveyed for patients who showed onset of major depression with melancholic features while taking an antidepressant medication. Nine cases resulted. In all the antidepressants being taken while melancholia began were SSRIs and the melancholic depression remitted rapidly with the first treatment given, bupropion in five males, nortriptyline with triiodothyronine in two females, and ECT in one male and one female. This suggests that patients who take SSRIs and are melancholic respond well to bupropion, nortriptyline, or ECT These observations complement reports of low responsivity of melancholic depression to SSRIs and distinctions between melancholic and nonmelancholic depressions.     

β-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo

Summary The cocaine analogue 2--carbomethoxy-3--(4-iodophenyl)-tropane (-CIT) is a potent ligand for both dopamine- and serotonin uptake sites which in its¹²³I labeled form can be used for single photon emission computerized tomography (SPECT). It was demonstrated previously by SPECT-studies in non-human primates that¹²³I--CIT binds to dopamine transporters in the striatum and to serotonin transporters in hypothalamus and midbrain. The aim of the present study was to compare¹²³I--CIT binding in the brain stem of normal controls and a group of subjects under treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram.¹²³I--CIT- SPECT was performed in 12 depressed patients under 20 mg (n=5), 40 mg (n=6) and 60 mg (n=1) citalopram daily, in one untreated depressed patient and in 11 controls at regular time intervals up till 24 hours p.inj. A highly significant reduction of -CIT binding was found in an area including mesial thalamus, hypothalamus, midbrain and pons in patients under citalopram compared to controls (44.1 ± 14.4 vs. 82.3 ± 18.6 cpm's/mCi × kg body weight; specific binding 4 hrs p.inj.; p=0.0001). No differences were seen between the high and low dose group and no changes were found in the striatum.¹²³I--CIT binding in the brain stem and striatum in one untreated depressed patient fell within the range of control values.To our knowledge this is the first report directly demonstrating the effect of a selective serotonin uptake inhibitor in the brain in humans in vivo. SPECT measurements of serotonin uptake sites in patients with depression and other psychiatric disorders might provide better insights into the pathophysiology of these disorders and into mechanisms of drug action.