Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model

Bone wound healing is a highly dynamic and precisely controlled process through which damaged bone undergoes repair and complete regeneration. External factors can alter this process, leading to delayed or failed bone wound healing. The findings of recent studies suggest that the use of selective serotonin reuptake inhibitors(SSRIs) can reduce bone mass, precipitate osteoporotic fractures and increase the rate of dental implant failure. With 10% of Americans prescribed antidepressants, the potential of SSRIs to impair bone healing may adversely affect millions of patients’ ability to heal after sustaining trauma. Here, we investigate the effect of the SSRI sertraline on bone healing through pre-treatment with(10 mg·kg-1sertraline in drinking water, n = 26) or without(control, n = 30) SSRI followed by the creation of a 5-mm calvarial defect. Animals were randomized into three surgical groups:(a) empty/sham,(b) implanted with a DermaMatrix scaffold soak-loaded with sterile PBS or(c) DermaMatrix soak-loaded with542.5 ng BMP2. SSRI exposure continued until sacrifice in the exposed groups at 4 weeks after surgery. Sertraline exposure resulted in decreased bone healing with significant decreases in trabecular thickness, trabecular number and osteoclast dysfunction while significantly increasing mature collagen fiber formation. These findings indicate that sertraline exposure can impair bone wound healing through disruption of bone repair and regeneration while promoting or defaulting to scar formation within the defect site.

Single-run reversed-phase HPLC method for determining sertraline content,enantiomeric purity,and related substances in drug substance and finished product

A direct enantio-,diastereo-,and chemo-selective high-performance liquid chromatographic method was developed for determining the content,enantiomeric purity,and related substances of the chiral antidepressant drug sertraline HCl in a single chromatographic run.The separation was achieved on a chiral stationary phase based on amylose tris(3-chloro-5-methylphenylcarbamate)under reversed-phase conditions.The method was optimized by evaluating the influence of the temperature and mobile phase composition on the retention and selectivity.The application of the single-run approach allowed to baseline resolve all investigated species in less than 15 min,without using buffers or tandem-coupled columns.The chromatographic method was validated according to the guidelines of the Official Medicines Control Laboratory and applied to control the content of sertraline HCl and related chiral substances in a generic antidepressant formulation.

Comparative study of on-demand and daily use of sertraline in treatment of premature ejaculation:A randomized clinical trial

Objective:The intravaginal ejaculatory latency time(IELT)may increase less in on-demand compared to daily intake,but may fulfill a suitable treatment for specific patients.We decided to compare the efficacy and safety of on-demand and daily use of sertraline in order to find the most effective and least complicated method in treatment of premature ejaculation(PE).Methods:This study was parallel or concurrent control randomized clinical trial.Two hundred and forty patients with PE diagnosed by urologist in the two groups of 120 from July 2017 to February 2019 enrolled in the study.In the first group,it is prescribed 50 mg sertraline each 12 h daily and the second group received 50 mg 4 h before coitus for 4 and 8 weeks.The IELT before treatment and during all coitus after treatment were recorded by the patient’s wife with a stopwatch.Results:Mean IELT before,4 and 8 weeks after treatment in two groups were:On-demand group 101.62±65.44 s,208.75±128.02 s and 265.87±145.70 s;daily use group 102.50-81.22 s,276.87±181.08 s and 353.75±176.45 s,respectively.The ejaculation time increased significantly in both groups(p<0.05).However,increase in ejaculation time in daily use group was significantly higher than the on-demand group in 4 weeks(p=0.036),especially in 8 weeks(p=0.009).The percent of side effects in daily use group(26.7%)was higher than on-demand group(20%)(p<0.05).Drowsiness,diarrhea and vertigo were significantly higher in the daily use than on-demand(p<0.05).Conclusions:On-demand and daily use of sertraline are effective and usually have no serious complications,but the on-demand method is considerably more tolerable.In patients who did not tolerate to daily use of this drug,on-demand could be used as a salvage therapy.

Effects of Sertraline on Sperm Motility, Number and Viability and Its Relation to Blood Levels of Testosterone, FSH and LH in Adult Male Mice

The aim of this study was to investigate the effects of Sertraline on gonad-pituitary cycle (Testosterone, FSH and LH) and reproductive cells in adult male Balb/C mice. Adult male Balb/C mice were divided into the following 5 groups: control group with no treatment, sham group which received solvent, and the experimental groups which received one dose of Sertraline (0.0178 mg/kg) in the first group, two doses of Sertraline (0.0356 mg/kg) in the second group, and three doses of Sertraline (0.0534 mg/kg) in the third group. Mice were anaesthetized after 7 weeks. Serum samples were collected and Testosterone, FSH and LH levels of serum were assayed. Vase deferans were analyzed for motility, number and viability of sperms. The results of this study showed that the viability, count and motility of sperms were decreased. Testosterone level of blood was also decreased while FSH was increased. There was no significant change in LH level. It is suggested that Sertraline at higher dose decreases sperm production and has the potential to affect adversely fertility in male mice.

Sertraline Induced Acute Hepatitis: A Case Report

Depression is a common disorder amongst the general population and frequently encountered by most physicians. Selective Serotonin Re-Uptake Inhibitors (SSRI’s) have become the most commonly prescribed antidepressants due to their superiority compared with other antidepressants in the treatment of acute major depression. Although exceedingly rare, hepatotoxicity resulting from sertraline use has been previously reported. In these case reports, the liver injury pattern was predominately hepatocellular. Unlike previous cases, we report the case of a patient presenting with markedly elevated cholestatic enzymes and painless jaundice while taking sertraline for treatment of depression.

Sertraline-induced reproductive toxicity in male rats： evaluation of possible underlying mechanisms

This study was conducted to clarify the toxic effects of sertraline （SRT） on the reproductive system of male rats and to elucidate the underlying mechanisms. Rats were treated orally with SRT at doses of 5, 10, and 20 mg kg-1 for 28 consecutive days. At the end of the treatment period, sperm concentration, sperm motility, and sperm morphology were investigated by computer-assisted sperm analysis system whereas sperm DNA damage was detected by comet assay. The oxidative status of the testes was investigated, and a histopathological examination was conducted. Serum testosterone, follicle-stimulating hormone （FSH）, and luteinizing hormone （LH） levels were measured to determine the effects of SRT on the spermatogenesis process. One-way ANOVA, post-hoc Dunnett＇s T3 test for the sperm comet assay, and post-hoc Tukey＇s test for the others were performed for statistical analysis. The results showed that SRT caused an increase in sperm DNA damage and induced histopathological lesions in all groups treated with SRT. There was abnormal sperm morphology and increased malondialdehyde （MDA） in the 10 mg kg-1 treatment group. More dramatic changes were observed in the 20 mg kg-1 treatment group. Decreased sperm count was accompanied by a significant increase in abnormal sperm morphology, DNA damage, and degeneration in cellular-tubular structures. Serum LH and testosterone levels were elevated in the 20 mg kg-~ treatment group. Decreased glutathione （GSH） and increased MDA were signs of enhanced oxidative stress （OS）. In conclusion, SRT induced testicular toxicity in a dose-dependent manner and OS is suggested as a crucial mechanism.

Evaluation on monoamine neurotransmitters changes in depression rats given with sertraline, meloxicam or/and caffeic acid

Inflammation drives the development of depression and may affect neurotransmitters and thus neurocircuits increase the risk of depression.To investigate the influence of inhibition of inflammatory pathways on the biogenic amine neurotransmitters metabolism in depressive rats,sertraline,and meloxicam,the inhibitors of arachidonic acid-cyclooxygenase-2/lipoxygenase(AA-COX-2/5-LO)pathways,were given to depressive rats.After the development of depression model by chronic unpredictable mild stress(CUMS)for 6 weeks,Successful modeling rats were selected and randomly divided into CUMS group and medication administration group.After given medicine,The biogenic amine neurotransmitters in rat cortex and hippocampus were measured by high-performance liquid chromatography equipped with an electrochemical detector(HPLC-ECD).Compared with the normal group,the concentration of norepinephrine(NE)significantly decreased and the concentrations of Tyrosine(Tyr),Tryptophan(Trp),3,4-dihydroxyphenyl acetic acid(DOPAC),3-methoxy-4-hydroxyphenylglycol(MHPG),homovanillic acid(HVA)and 5-hydroxyindoleacetic acid(5-HIAA)significantly increased in the CUMS group.Sertraline significantly inhibited the elevation of 5-HIAA.Meloxicam inhibited the decrease of NE level in CUMS-induced rat and the increase of Trp,MHPG,and 5-HIAA level in a dose-dependent manner.Caffeic acid inhibited the decrease of NE and the increase of Trp and MHPG in a dose-dependent manner.The inhibition of AA-COX-2/5-LO pathways can improve the behaviors of depression rats and suppress CUMSinduced changes in biogenic amines.Compared with the single-dose lipoxygenase(5-LO)or Cyclooxygenase-2(COX-2)inhibitor,the combination treatment with meloxicam 1 mg/kg and caffeic acid 10 mg/kg have no significant improvement in CUMS-induced depression behavior and the level of cortical monoamine neurotransmitters and their metabolites.

Comparison between cannabidiol and sertra⁃line in modulation of post-traumatic stress dis⁃order-like behaviors and fear memory in mice

OBJECTIVE Post-traumatic stress disorder(PTSD)is characterized by poor adapta⁃tion to a traumatic experience and disturbances in fear memory regulation,and currently lacks effective medication.Cannabidiol(CBD)is the primary component of the Cannabis sativa plant;it does not have any psychoactive effects and has been implicated in modulating fear learning in mammals.The present study investigated the effect of CBD on PTSD-like behaviors in a mouse pre-shock model,the effect of CBD in the modulation of trauma-related fear memory,a crucial process leading to core symptoms of PTSD.METHODS Pre-shock model was applied in which mice were submitted to training with two days of 0.8 mA×12 times of foot-shock,and PTSD-like behaviors was evaluated during 3 and 26 d,including freezing time to the conditioned context,open field test,elevated plus maze test and social interaction test.RESULTS CBD(10 mg·kg^(-1))administration alleviated main PTSD-like symptoms in the mouse pre-shock model by attenuating trauma-related fear memory,decreasing anxiety-like behavior,and increasing social interaction behavior.However,sertraline(15 mg·kg^(-1))was only effective when adminis⁃tered throughout the test period.Furthermore,CBD reduced the formation,retrieval,and recon⁃solidation of trauma-related fear memory,whereas sertraline only reduced fear-memory retrieval.Neither CBD nor sertraline influenced the acquisi⁃tion of trauma-related fear memory.CONCLU⁃SION CBD produced anti-PTSD-like actions in mice,and could disrupt trauma-related fear mem⁃ory by interfering with multiple aspects of fear memory processing in mice.These findings indi⁃cate that CBD may be a promising candidate for treating PTSD.

Sex-Dependent Effects of Prenatal Stress on Learned Helplessness and Anxiety-Related Behaviours in Wistar Rats

There has been an increasing importance of studies that link sex to stress coping processes. Recently, we reported that male and female Wistar rats responded differently to prenatal stress (PS) under basal conditions. The aim of the present study was to determine the influence of sex on behaviour and coping strategies, as an effect of gestational adversity in rats that were exposed to an uncontrollable stressor. Once the animals reached adulthood, the offspring from stressed/non-stressed dams were subjected or not to antidepressant treatment with Sertraline. After that, they were exposed to a single inescapable shock (IS) session, in which the rats were further tested for escape behaviour along 10 days, as a model of learned helplessness (LH). In prenatally stressed animals after the IS, behavioural differences appeared in a sex specific manner. Males proved to be more susceptible to the adverse context than females, exhibiting behavioural despair in a large percentage of the cases. Surprisingly, PS did not affect shock escape failure, but did affect learning performance in a sex dependent manner. In females, PS led them to learn to avoid shocks, learning better than controls, and by contrast, PS males did not learn to avoid shocks and displayed some signs of anhedonia. Sertraline did not help animals to avoid shocks, but helped them to escape from it. Our data indicate the existence of sex dependent behavioural differences in PS animals when facing an uncontrollable stress situation, in which the changes induced by PS were not only different, but opposite between sexes.

Serotonin syndrome and acute hyponatremia, complex overlapping syndromes, a case report and review

Objective: To report the first case of simultaneous serotonin syndrome and acute hyponatremia secondary to sertraline and drug interactions resulting in patients’ death (Naranjo ADR probability score 7). Case Summary: An 83-year-old female on sertraline for 5 years for depression was admitted for left tibial plateau fracture. She had a history of short bowel syndrome, total parenteral nutrition and CKD stage 3 secondary to vascular disease. 2 weeks post operatively, she developed into difficulty concentrating, tachycardia, hyperreflexia and clonus in context of opioids and antiemetic use but was afebrile and haemodynamically stable. She also developed into acute hyponatremia from 133 mmol/L to 127 mmol/L within 24 hours. Sertraline and antiemetic medications were stopped and cyproheptadine and diazepam were started to treat serotonin syndrome. The patient deteriorated after an initial improvement. She developed into aspiration pneumonia later and passed away in ICU. Discussion: Both acute hyponatremia and serotonin syndrome share SSRIs as common etiology, which have acute onset and rapid resolution and show multiple overlapping neurological features. Hunter criteria are more accurate than Sternbach criteria due to less emphasis on mental features to diagnose serotonin syndrome with overlapping conditions with similar presentation. Hyponatremia causes muscle weakness with hyporeflexia compared to serotonin syndrome with hyperreflexia and clonus. Conclusion: Clinicians should be aware of possibility of both acute hyponatremia and serotonin syndrome secondary to SSRIs interacting with opioids and ondansetron. The use of Hunter criteria would aid in prompting diagnosis and initiation of timely treatment.