The use of sertraline to treat an adolescent of dystonia comorbid with major depressive disorder with psychotic features.

Dystonia is characterized by sustained or intermittent involuntary muscle contractions. Psychiatric symptoms are essential non-motor features of dystonia, and higher risks of depressive and anxiety disorders have been reported. The precedence of psychiatric to motor symptoms in some patients and the dopaminergic and serotonergic system involvement in both the motor and psychiatric aspects suggest these psychiatric disorders may be intrinsic to the neurobiology of dystonia. Nevertheless, psychiatric comorbidities are often construed as secondary reactions to motor disabilities and the negative bio-psycho-social impacts of dystonia, leading to underdiagnosis and undertreatment. Research on antidepressant use in dystonia is scarce, especially in children and adolescents. This report presents a 17-year-old female with dystonia comorbid with depression with psychotic features, whose motor symptoms improved but psychiatric symptoms persisted with dopaminergic pharmacotherapy. Sertraline was finally added 5 years after the onset and successfully managed her psychotic depression without worsening motor symptoms. Early detection, prompt diagnosis, and timely holistic treatment with dopaminergic agents, antidepressants, and psychosocial interventions are critical for the mental health of dystonia patients.

From Waterloo to the Great Wall: A retrospective, multicenter study on the clinical practice and cultural attitudes in the management of premature ejaculation, in China.

Premature ejaculation (PE), despite its wide prevalence, is largely underdiagnosed and undertreated. Being a multifactorial dysfunction with strong cultural characteristics, PE requires skillful attitudes in the psychosexological support, necessary to manage the patient's and the couple's expectations, as well as in the medical treatment. Dapoxetine is a short-acting selective serotonin reuptake inhibitor approved for use in lifelong and acquired PE in a number of countries. Opinions, not always generated by the evidence-based medicine, impacted the attitudes of Western andrologists, as a nocebo effect which produced a drug's Waterloo, characterized by low prescription rates much more built on the patients' and doctors' expectations than on costs, side effects, and efficacy. In the present study, we retrospectively reviewed real-life data from eight Andrology and Sexual Medicine Public Centers in China to assess the prevalence of PE among attending patients, its association with erectile dysfunction, its subtype, and the proposed treatments. In 2019, among 156,486 patients coming to the centers, 32,667 visits having PE as the chief complaint were performed (20.9%). Almost all patients received treatment prescriptions (32,641 patients, 99.92%); 23,273 patients came back for a follow-up visit in the subsequent 12 months (71.2% of those who initially received treatment). Dapoxetine, either alone or in combination with another therapy, was the most prevalent treatment, prescribed to 22,767 patients (69.7% of treated patients), followed by traditional Chinese medicine (TCM) (39.4%). At follow-up, 8174 patients were unsatisfied with treatment, and a new treatment was proposed (35.12%). Dapoxetine was the best treatment, with an overall 27.1% switching rate when used either alone or in combination: Although the switching rate for Dapoxetine alone was 44.2%, the association of the same drug with psychotherapy resulted in much lower rates (19.5%) and reached a minimum of 12% when also combined with TCM demonstrating how cultural aspects and medical attitudes may dramatically impact on the therapy of a multifaceted, complex, and culture-grounded sexual symptom such as PE. In conclusion, taking switching rates as surrogate markers of treatment failure, this real-life study-the largest in the field-shows that in a more patient-oriented (as in Chinese medical culture), and less symptom-oriented (as in Western medical attitudes), Dapoxetine is a successful treatment for PE patients, with higher reliability when used alone or as part of combined and integrated therapies.

Fluoxetine treatment during the postpartal period may have short-term impacts on murine maternal skeletal physiology.

Postpartum depression affects many individuals after parturition, and selective serotonin reuptake inhibitors (SSRIs) are often used as the first-line treatment; however, both SSRIs and lactation are independently associated with bone loss due to the role of serotonin in bone remodeling. Previously, we have established that administration of the SSRI fluoxetine during the peripartal period results in alterations in long-term skeletal characteristics. In the present study, we treated mice with either a low or high dose of fluoxetine during lactation to determine the consequences of the perturbation of serotonin signaling during this time period on the dam skeleton. We found that lactational fluoxetine exposure affected both cortical and trabecular parameters, altered gene expression and circulating markers of bone turnover, and affected mammary gland characteristics, and that these effects were more pronounced in the dams that were exposed to the low dose of fluoxetine in comparison to the high dose. Fluoxetine treatment during the postpartum period in rodents had short term effects on bone that were largely resolved 3 months post-weaning. Despite the overall lack of long-term insult to bone, the alterations in serotonin-driven lactational bone remodeling raises the question of whether fluoxetine is a safe option for the treatment of postpartum depression.

Effects of Aphrodite (an Herbal Compound) on SSRI-Induced Sexual Dysfunctions and Depression in Females with Major Depressive Disorder: Findings from a Randomized Clinical Trial.

Background and Objectives: Almost by default, people with major depression disorder (MDD) also report sexual health issues. This holds even more true when sexual dysfunctions are SSRI-induced. Herbal compounds may have the power to counterbalance such sexual dysfunctions, though research is still scarce. Therefore, we assessed females with diagnosed MDD treated with a standard SSRI (sertraline) and reporting SSRI-induced sexual dysfunctions, and we asked whether compared to placebo, Aphrodite (a blend of ginger, saffron, cinnamon, thistle, and Tribulus terrestris) may favorably impact on sexual dysfunctions, and on symptoms of depression, anxiety, and sleep disturbances. Materials and Methods: A total of 41 females (mean age: 35.05 years) with diagnosed MDD, treated with sertraline (a standard SSRI) at therapeutic dosages, and reporting SSRI-induced sexual dysfunction, were randomly assigned either to Aphrodite or to the placebo condition. At baseline and four and eight weeks later (study end), participants completed a series of self-rating questionnaires covering symptoms of sexual dysfunction, depression, anxiety, and sleep complaints. Results: Symptoms of sexual dysfunction, depression, and anxiety decreased over time, but more so in the Aphrodite condition, compared to the placebo condition (significant p-values and large effect sizes). Over time, sleep disturbances decreased irrespective of the study condition. Conclusions: The pattern of results suggests that compared to placebo, Aphrodite appeared to improve symptoms of sexual dysfunction, depression, and anxiety among females with diagnosed MDD and SSRI-induced sexual dysfunction. Further and similar studies should investigate the underlying psychophysiological mechanisms.

Assessing the effect of Alpinia galanga extract on the treatment of SSRI-induced erectile dysfunction: A randomized triple-blind clinical trial.

Objective: SSRIs are considered the first line in the medical treatment of depression and anxiety disorders. One of their most common side effects, sexual dysfunction, has led many patients to discontinuing their medication and treatment course. Alpinia galanga, a plant from the ginger family, has been shown to enhance androgenic activity and sexual function. This study aimed to assess whether the addition of Alpinia galanga extract to the treatment regimen of adult males consuming SSRIs can improve SSRI-induced erectile dysfunction. Materials and methods: This triple-blind randomized clinical trial was conducted on 60 adult males who were being treated with SSRIs at the time of the study. The participants were divided into two groups, a group of 30 people receiving 500 mg of Alpinia galanga extract and a group of 30 subjects receiving placebo. The population were re-assessed on week 2 and week 4 of the study using the international index of erectile function (IIEF), the Beck Depression Inventory, and the Beck Anxiety Inventory. In all the tests, a p-value of 0.05 was considered as the cut-off for significance. Results: At the beginning of the study, the IIEF scores of the placebo group and the intervention group were 10.6 ± 3.8 and 11.2 ± 4.8, respectively, which were not significantly different (p-value = 0.577). By week 4 of the study, the IIEF scores of the control group and the Alpinia galanga group had increased to 13.7 ± 4.3 and 17.4 ± 3.7 respectively, which demonstrates a remarkably larger increase in the group receiving Alpinia galanga extract in comparison to the placebo group (p-value < 0.001). Conclusion: In this study, the effect of the addition of Alpinia galanga extract to the treatment regimen of male patients using SSRIs on the sexual dysfunction experienced by this group has been promising. Similar results, if proven, can aid both patients and clinicians in making and following better treatment plans with more pleasant outcomes. Clinical trial registration: [https://clinicaltrials.gov/], identifier [IRCT20101130005280N41].

SSRI/SNRI -induced Hyponatremia: A Case Series of 26 Patients in a Single Institution from 2018 to 2020.

Antidepressant medications are widely used by patients with depression or a depressive disorder. In spite of a generally favorable safety profile of selective serotonin reuptake inhibitors or serotonin - norepinephrine reuptake inhibitors (SSRI/SNRI), several cases of a possible connection between SSRI/SNRI and hyponatremia have been reported. To describe the clinical characteristics of patients with hyponatremia after SSRI/SNRI exposure, and to examine the association between SSRI/SNRI exposure and the presence of hyponatremia in a Chinese population. A retrospective single-center case series study. We performed a retrospective evaluation of inpatients with SSRI/SNRI-induced hyponatremia from a single institution in China between 2018 and 2020. Clinical data were obtained through review of medical records. Patients who met the initial inclusion criteria but did not develop hyponatremia acted as controls. The study was approved by the Clinical Research Ethics Board of Beijing Hospital (Beijing, P.R. China). We identified 26 patients with SSRI/SNRI-induced hyponatremia. The incidence rate of hyponatremia was 1.34% (26/1937) in the study population. The mean age at diagnosis was 72.58 (±12.84) years, with a male: female ratio of 1:1.42. The duration between SSRI/SNRI exposure and the onset of hyponatremia was 7.65 (±4.88) days. The minimum serum sodium level was 2328.23 (±107.25) mg/dL in the study group. Seventeen patients (65.38%) received sodium supplements. Four patients (15.38%) switched to another antidepressant. Fifteen patients (57.69%) recovered by the time of discharge. There were significant differences in serum potassium, serum magnesium and serum creatinine level between the two groups (p < 0.05). The rate of use of sertraline was significantly higher in the study group compared with the control group (p < 0.05). This pattern was not found in other SSRI/SNRI (p > 0.05). The results of our study show that SSRI/SNRI exposure, in addition to hyponatremia, may also affect the level of serum potassium, serum magnesium and serum creatinine. A history of hyponatremia and exposure to SSRI/SNRI may be potential risk factors for the development of hyponatremia. Future prospective studies are needed to validate these findings.

The Effect of SSRI Exposure in Pregnancy on Early Respiratory and Metabolic Adaptation in Infants Born Preterm.

Selective serotonin reuptake inhibitors (SSRIs) are increasingly used for maternal depression during pregnancy; however, their use has been linked to adverse effects in newborns. Respiratory and feeding problems, jaundice, metabolic and temperature dysregulation and hypoglycemia have been described in term infants. However, scarce data exists on early neonatal adaptation in exposed infants born prematurely. We aimed to assess the effects of SSRI exposure on early neonatal adaptation measures in infants born prematurely. Data from preterm infants exposed to maternal SSRIs during pregnancy and from matched controls were retrospectively collected. Forty-two infants comprised the final cohort: 21 infants with SSRI exposure and 21 matched controls. 1 min Apgar score was significantly lower in the exposed group compared to the non-exposed group (p = 0.043). No differences were found in 5 min Apgar scores, cord pH, need for delivery room resuscitation, rate of hypoglycemia, hyponatremia, hyperbilirubinemia, need for phototherapy, temperature stability and maximal oxygen requirements. No differences were found in the total time of respiratory support, time to reaching full enteral feeds, length of stay and complications of prematurity. Unlike studies in term infants, no significant differences were found in adaptation and short-term outcomes between preterm infants with and without SSRI exposure in pregnancy.

Does acupuncture therapy affect peripheral inflammatory cytokines of major depressive disorder? A protocol for the systematic review and meta-analysis.

Background: Acupuncture is widely used as adjuvant therapy for major depressive disorder (MDD). There is robust evidence that inflammation is closely associated with MDD. To date, only a few numbers of studies have investigated the potential relationship between acupuncture and the change of inflammatory biomarkers in patients with MDD. Additionally, the results are inconsistent among studies. The current study aims to provide a comprehensive, systematic review of the association between acupuncture and changes in peripheral inflammation of patients with MDD, and clarify the alterations of inflammatory cytokines before and after acupuncture treatment by meta-analysis. Methods and analysis: This study will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible randomized controlled trials (RCTs) reporting acupuncture, with inflammatory cytokines as the outcome measured before and after intervention in patients with MDD, were searched in electronic databases, such as PubMed, Embase, Cochrane, SINOMED, Wanfang, China national knowledge infrastructure (CNKI), and Chongqing VIP (CQVIP). Primary outcomes of interest will be validated to measure the levels of inflammatory cytokines before and after acupuncture treatment in patients with MDD. Discussion: Acupuncture can drive anti-inflammatory effects, as well as symptom changes in MDD, which may represent a viable, multi-faceted treatment approach in MDD. Systematic review registration: [PROSPERO], identifier [CRD42021289207 on 04 December 2021].

Impact of Fluoxetine Treatment and Folic Acid Supplementation on the Mammary Gland Transcriptome During Peak Lactation.

Serotonin is a key regulator of mammary gland homeostasis during lactation. Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat peripartum depression, but also modulates mammary gland serotonin concentrations and signaling in part through DNA methylation. The objective of this study was to determine mouse mammary transcriptome changes in response to the SSRI fluoxetine and how methyl donor supplementation, achieved by folic acid supplementation, affected the transcriptome. Female C57BL/6J mice were fed either breeder diet (containing 4 mg/kg folic acid) or supplemented diet (containing 24 mg/kg folic acid) beginning 2 weeks prior to mating, then on embryonic day 13 mice were injected daily with either saline or 20 mg/kg fluoxetine. Mammary glands were harvested at peak lactation, lactation day 10, for transcriptomic analysis. Fluoxetine but not folic acid altered circulating serotonin and calcium concentrations, and folic acid reduced mammary serotonin concentrations, however only fluoxetine altered genes in the mammary transcriptome. Fluoxetine treatment altered fifty-six genes. Elovl6 was the most significantly altered gene by fluoxetine treatment along with gene pathways involving fatty acid homeostasis, PPARγ, and adipogenesis, which are critical for milk fat synthesis. Enriched pathways in the mammary gland by fluoxetine revealed pathways including calcium signaling, serotonin receptors, milk proteins, and cellular response to cytokine stimulus which are important for lactation. Although folic acid did not impact specific genes, a less stringent pathway analysis revealed more diffuse effects where folic acid enriched pathways involving negative regulation of gene expression as expected, but additionally enriched pathways involving serotonin, glycolysis, and lactalbumin which are critical for lactation. In conclusion, peripartal SSRI use and folic acid supplementation altered critical genes related to milk synthesis and mammary gland function that are important to a successful lactation. However, folic acid supplementation did not reverse changes in the mammary gland transcriptome altered by peripartal SSRI treatment.

Sex-Based Impact of Creatine Supplementation on Depressive Symptoms, Brain Serotonin and SSRI Efficacy in an Animal Model of Treatment-Resistant Depression.

BACKGROUND: Rates of major depressive disorder (MDD) increase with living at altitude. In our model, rats housed at moderate altitude (in hypobaric hypoxia) exhibit increased depression-like behavior, altered brain serotonin and a lack of antidepressant response to most selective serotonin reuptake inhibitors (SSRIs). A forebrain deficit in the bioenergetic marker creatine is noted in people living at altitude or with MDD. METHODS: Rats housed at 4500 ft were given dietary creatine monohydrate (CRMH, 4% w/w, 5 weeks) vs. un-supplemented diet, and impact on depression-like behavior, brain bioenergetics, serotonin and SSRI efficacy assessed. RESULTS: CRMH significantly improved brain creatine in a sex-based manner. At altitude, CRMH increased serotonin levels in the female prefrontal cortex and striatum but reduced male striatal and hippocampal serotonin. Dietary CRMH was antidepressant in the forced swim test and anti-anhedonic in the sucrose preference test in only females at altitude, with motor behavior unchanged. CRMH improved fluoxetine efficacy (20 mg/kg) in only males at altitude: CRMH + SSRI significantly improved male striatal creatine and serotonin vs. CRMH alone. CONCLUSIONS: Dietary CRMH exhibits sex-based efficacy in resolving altitude-related deficits in brain biomarkers, depression-like behavior and SSRI efficacy, and may be effective clinically for SSRI-resistant depression at altitude. This is the first study to link CRMH treatment to improving brain serotonin.

Folate as adjunct therapy to SSRI/SNRI for major depressive disorder: Systematic review & meta-analysis.

OBJECTIVE: Evaluate depression scores, response, and remission rates in patients with major depression receiving adjunct therapy with folate (L-Methylfolate or folic acid) compared to selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor (SSRI or SNRI) monotherapy. METHODS: Academic Search Premier, CINAHL Complete, Cochrane Database of Systematic Reviews, Medline with Full Text, PsychInfo, PubMed, ClinicalTrials.org, and Google Scholar were searched utilizing specific key words. Identified studies were independently screened for inclusion by two reviewers, were assessed for risk of bias using the Revised Cochrane risk-of-bias tool (RoB2), then meta-analyzed using a random effects model with Review Manager (5.4) software. RESULTS: The initial search revealed 293 articles with 6 randomized control trials ultimately meeting inclusion criteria. In patients with depression, analysis of 5 studies revealed a significantly lower Hamilton Depression Rating Scale (HAM-D) score in individuals treated with adjunct therapy with l-Methylfolate/folic acid [Mean Difference (MD): -2.16 (95 % CI -3.62 to -0.69), p = 0.004], as well a combined HAM-D and Beck Depression Inventory-II (BDI-II) scores [standardized mean difference (SMD): -0.61 (95 % Confidence Interval {CI} -0.97 to -0.24), p = 0.002]. This adjunct therapy also yielded an improved response rate [Risk Ratio (RR): 1.36 (95 % CI: 1.16-1.59) P = 0.0001], increase in remission rate [RR: 1.39 (95 % CI: 1.00-1.92) P = 0.05], and reduction in depression scores after varying durations of treatment, 4 week: [SMD = -0.38 (95 % CI: -0.55 to -0.22) P ≤ 0.00001]; 6 week: [SMD = -0.94 (95 % CI: -1.85 to -0.03) P = 0.04]; ≥ 8 week: [SMD= -0.57 (95 % CI: -0.91 to -0.23) P = 0.0009]. CONCLUSION: Adjunct therapy with l-Methylfolate or folic acid improves depression scale scores, patient response, and remission rates.

Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?

Different mechanisms forwarded to understand anosmia and ageusia in coronavirus patients are not adequate to explain reversible anosmia and ageusia, which are resolved quickly. In addition, the reason behind the impaired chemesthetic sensations in some coronavirus patients remains unknown. In the present paper it is proposed that SARS-CoV-2 patients suffer from depletion of tryptophan, as ACE2, a key element in the process of absorption of tryptophan from the food, is significantly reduced in the patients as coronavirus uses ACE2 as the receptor to enter the host cells. The tryptophan depletion leads to a deficit of serotonin (5-HT) in SARS-COV-2 patients because tryptophan is the precursor in the synthesis of 5-HT. Such 5-HT deficiency can explain anosmia, ageusia and dysfunctional chemesthesis in COVID-19, given the fact that 5-HT is an important neuromodulator in the olfactory neurons, taste receptor cells and transient receptor potential channels (TRP channels) involved in chemesthesis. In addition, 5-HT deficiency worsens silent hypoxemia and depresses hypoxic pulmonary vasoconstriction leading to increased severity of the disease. Also, the levels of anti-inflammatory melatonin (synthesized from 5-HT) and nicotinamide adenine dinucleotide (NAD+, produced from niacin whose precursor is the tryptophan) might decrease in coronavirus patients resulting in the aggravation of the disease. Interestingly, selective serotonin reuptake inhibitors (SSRIs) may not be of much help in correcting the 5-HT deficiency in COVID-19 patients, as their efficacy goes down significantly when there is depletion of tryptophan in the system. Hence, tryptophan supplementation may herald a radical change in the treatment of COVID-19 and accordingly, clinical trials (therapeutic / prophylactic) should be conducted on coronavirus patients to find out how tryptophan supplementation (oral or parenteral, the latter in severe cases where there is hardly any absorption of tryptophan from the food) helps in curing, relieving or preventing the olfactory, gustatory and chemesthetic dysfunctions and in lessening the severity of the disease.

Cannabis and cannabidiol (CBD) for the treatment of fibromyalgia.

Fibromyalgia is a complex disease process that is as prevalent as it is poorly understood. Research into the pathophysiology is ongoing, and findings will likely assist in identifying new therapeutic options to augment those in existence today that are still insufficient for the care of a large population of patients. Recent evidence describes the use of cannabinoids in the treatment of fibromyalgia. This study provides a systematic, thorough review of the evidence alongside a review of the seminal data regarding the pathophysiology, diagnosis, and current treatment options. Fibromyalgia is characterized by widespread chronic pain, fatigue, and depressive episodes without an organic diagnosis, which may be prevalent in up to 10% of the population and carries a significant cost in healthcare utilization, morbidity, a reduced quality of life, and productivity. It is frequently associated with psychiatric comorbidities. The diagnosis is clinical and usually prolonged, and diagnostic criteria continue to evolve. Some therapies have been previously described, including neuropathic medications, milnacipran, and antidepressants. Despite some level of efficacy, only physical exercise has strong evidence to support it. Cannabis has been used historically to treat different pain conditions since ancient times. Recent advances allowed for the isolation of the active substances in cannabis and the production of cannabinoid products that are nearly devoid of psychoactive influence and provide pain relief and alleviation of other symptoms. Many of these, as well as cannabis itself, are approved for use in chronic pain conditions. Evidence supporting cannabis in chronic pain conditions is plentiful; however, in fibromyalgia, they are mostly limited. Only a handful of randomized trials exists, and their objectivity has been questioned. However, many retrospective trials and patient surveys suggest the significant alleviation of pain, improvement in sleep, and abatement of associated symptoms. Evidence supporting the use of cannabis in chronic pain and specifically in fibromyalgia is being gathered as the use of cannabis increases with current global trends. While the current evidence is still limited, emerging data do suggest a positive effect of cannabis in fibromyalgia. Cannabis use is not without risks, including psychiatric, cognitive, and developmental as well as the risks of addiction. As such, clinical judgment is warranted to weigh these risks and prescribe to patients who are more likely to benefit from this treatment. Further research is required to define appropriate patient selection and treatment regimens.

Implementation research for public sector mental health care scale-up (SMART-DAPPER): a sequential multiple, assignment randomized trial (SMART) of non-specialist-delivered psychotherapy and/or medication for major depressive disorder and posttraumatic stress disorder (DAPPER) integrated with outpatient care clinics at a county hospital in Kenya.

BACKGROUND: Mental disorders are a leading cause of global disability, driven primarily by depression and anxiety. Most of the disease burden is in Low and Middle Income Countries (LMICs), where 75% of adults with mental disorders have no service access. Our research team has worked in western Kenya for nearly ten years. Primary care populations in Kenya have high prevalence of Major Depressive Disorder (MDD) and Posttraumatic Stress Disorder (PTSD). To address these treatment needs with a sustainable, scalable mental health care strategy, we are partnering with local and national mental health stakeholders in Kenya and Uganda to identify 1) evidence-based strategies for first-line and second-line treatment delivered by non-specialists integrated with primary care, 2) investigate presumed mediators of treatment outcome and 3) determine patient-level moderators of treatment effect to inform personalized, resource-efficient, non-specialist treatments and sequencing, with costing analyses. Our implementation approach is guided by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework. METHODS/DESIGN: We will use a Sequential, Multiple Assignment Randomized Trial (SMART) to randomize 2710 patients from the outpatient clinics at Kisumu County Hospital (KCH) who have MDD, PTSD or both to either 12 weekly sessions of non-specialist-delivered Interpersonal Psychotherapy (IPT) or to 6 months of fluoxetine prescribed by a nurse or clinical officer. Participants who are not in remission at the conclusion of treatment will be re-randomized to receive the other treatment (IPT receives fluoxetine and vice versa) or to combination treatment (IPT and fluoxetine). The SMART-DAPPER Implementation Resource Team, (IRT) will drive the application of the EPIS model and adaptations during the course of the study to optimize the relevance of the data for generalizability and scale -up. DISCUSSION: The results of this research will be significant in three ways: 1) they will determine the effectiveness of non-specialist delivered first- and second-line treatment for MDD and/or PTSD, 2) they will investigate key mechanisms of action for each treatment and 3) they will produce tailored adaptive treatment strategies essential for optimal sequencing of treatment for MDD and/or PTSD in low resource settings with associated cost information - a critical gap for addressing a leading global cause of disability. TRIAL REGISTRATION: ClinicalTrials.gov NCT03466346, registered March 15, 2018.

VITamin D and OmegA-3 TriaL (VITAL) bone health ancillary study: clinical factors associated with trabecular bone score in women and men.

We investigated the association of clinical variables with TBS at baseline in the bone health sub-cohort of the VITamin D and OmegA-3 TriaL (VITAL). Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, high alcohol intake, and presence of diabetes; there was a trend towards significance between lower TBS and history of fragility fractures. INTRODUCTION: We investigated whether TBS differs by sex, race, body mass index (BMI), and other clinical variables. METHODS: The VITamin D and OmegA-3 TriaL (VITAL) is determining effects of vitamin D3 and/or omega-3 fatty acid (FA) supplements in reducing risks of cancer and cardiovascular disease. In the VITAL: Effects on Bone Structure/Architecture ancillary study, effects of these interventions on bone will be investigated. Here, we examine the associations of clinical risk factors with TBS assessments at baseline in the bone health sub-cohort, comprised of 672 participants (369 men and 303 women), mean (± SD) age 63.5 ± 6.0 years; BMI ≤ 37 kg/m2, no bisphosphonates within 2 years or other bone active medications within 1 year. RESULTS: TBS was greater in men than women (1.311 vs. 1.278, P < 0.001) and lower with elevated BMIs (P < 0.001), higher age (P = 0.004), diabetes (P = 0.008), SSRI use (P = 0.044), and high alcohol intake (P = 0.009). There was a trend for history of fragility fractures (P = 0.072), and lower TBS. TBS did not vary when analyzed by race, smoking, history of falls, and multivitamin or caffeine use. CONCLUSIONS: Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, alcohol use, and presence of diabetes; there was a trend between lower TBS and history of fragility fractures. TBS may be useful clinically to assess structural changes that may be associated with fractures among patients who are overweight or obese, those on SSRIs, or with diabetes. Ongoing follow-up studies will clarify the effects of supplemental vitamin D3 and/or FA's on TBS and other bone health measures. TRIAL REGISTRATION: NCT01747447.

Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review.

INTRODUCTION: Generalized anxiety disorder (GAD) often begins during adolescence or early adulthood and persists throughout the lifespan. Randomized controlled trials support the efficacy of selective serotonin and selective serotonin norepinephrine reuptake inhibitors (SSRIs and SNRIs, respectively), as well as benzodiazepines, azapirones, anti-adrenergic medications, melatonin analogs, second-generation antipsychotics, kava, and lavender oil in GAD. However, psychopharmacologic treatment selection requires clinicians to consider multiple factors, including age, co-morbidity, and prior treatment. Areas covered: The authors review the literature concerning pharmacotherapy for pediatric and adult patients with GAD with specific commentary on the efficacy and tolerability of selected agents in these age groups. The authors describe an algorithmic approach to the pediatric and adult patient with GAD and highlight considerations for the use of selected medications in these patients. Expert opinion: In adults with GAD, SSRIs and SNRIs represent the first-line psychopharmacologic treatment while second-line pharmacotherapies include buspirone, benzodiazepines, SGAs, and pregabalin. In pediatric patients with GAD, SSRIs should be considered the first line pharmacotherapy and psychotherapy enhances antidepressant response.

Disordered eating and obesity: associations between binge-eating disorder, night-eating syndrome, and weight-related comorbidities.

Binge-eating disorder (BED) and night-eating syndrome (NES) are two forms of disordered eating associated with overweight and obesity. While these disorders also occur in nonobese persons, they seem to be associated with weight gain over time and higher risk of diabetes and other metabolic dysfunction. BED and NES are also associated with higher risk of psychopathology, including mood, anxiety, and sleep problems, than those of similar weight status without disordered eating. Treatments are available, including cognitive behavior therapy (CBT), interpersonal psychotherapy, lisdexamfetamine, and selective serotonin reuptake inhibitors (SSRIs) for BED; and CBT, SSRIs, progressive muscle relaxation, and bright light therapy for NES.

Antidepressants Rescue Stress-Induced Disruption of Synaptic Plasticity via Serotonin Transporter-Independent Inhibition of L-Type Calcium Channels.

BACKGROUND: Long-term synaptic plasticity is a basic ability of the brain to dynamically adapt to external stimuli and regulate synaptic strength and ultimately network function. It is dysregulated by behavioral stress in animal models of depression and in humans with major depressive disorder. Antidepressants have been shown to restore disrupted synaptic plasticity in both animal models and humans; however, the underlying mechanism is unclear. METHODS: We examined modulation of synaptic plasticity by selective serotonin reuptake inhibitors (SSRIs) in hippocampal brain slices from wild-type rats and serotonin transporter (SERT) knockout mice. Recombinant voltage-gated calcium (Ca2+) channels in heterologous expression systems were used to determine the modulation of Ca2+ channels by SSRIs. We tested the behavioral effects of SSRIs in the chronic behavioral despair model of depression both in the presence and in the absence of SERT. RESULTS: SSRIs selectively inhibited hippocampal long-term depression. The inhibition of long-term depression by SSRIs was mediated by a direct block of voltage-activated L-type Ca2+ channels and was independent of SERT. Furthermore, SSRIs protected both wild-type and SERT knockout mice from behavioral despair induced by chronic stress. Finally, long-term depression was facilitated in animals subjected to the behavioral despair model, which was prevented by SSRI treatment. CONCLUSIONS: These results showed that antidepressants protected synaptic plasticity and neuronal circuitry from the effects of stress via a modulation of Ca2+ channels and synaptic plasticity independent of SERT. Thus, L-type Ca2+ channels might constitute an important signaling hub for stress response and for pathophysiology and treatment of depression.

[Hyponatremia associated with SSRI/NRSI: Descriptive and comparative epidemiological study of the incidence rates of the notified cases from the data of the French National Pharmacovigilance Database and the French National Health Insurance]. / Les hyponatrémies sous ISRS/IRSNA : étude épidémiologique descriptive et comparative des taux d'incidence de cas notifiés à partir des données de la Banque nationale de pharmacovigilance et de l'Assurance maladie.

INTRODUCTION: Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are frequently prescribed. These antidepressants can potentially induce serious hyponatremia through the SIADH syndrome. That seems to concern all molecules of these classes but the individual risk of each molecule is not well known. The aims of the study were to compare the incidence rate of each molecule in order to identify the existence of molecules more at risk of inducing hyponatremia and to characterize a profile of patients at risk for hyponatremia during a treatment with a SSRI or a SNRI. METHOD: The cases of hyponatremia under SSRI/SNRI were extracted from the French pharmacovigilance database (BPNV). The exposition to the different SSRIs/SNRIs in the French population was estimated from the French National Health Insurance database (SNIIRAM) using a sampled database (Echantillon Généralistes des Bénéficiaires). The study ran from 01/01/2011 to 31/12/2013. The primary study endpoint was the incidence rate of notifications of the hyponatremia cases in patients treated by SSRI/SNRI and recorded into the BNPV database, related to the average annual number of corresponding treatments initiated during the same period. RESULTS: The number of cases of hyponatremia included in the study was 169 for 3 749 800 adult patients initiating treatment. The incidence rate of cases was 1.64 for 100 000 persons per year (PY). The standardized incidence rates between the different molecules showed no difference except for duloxetine (2.79/100 000 PY p > 0.03). Identified risk factors were age, with a large increase of incidence rate from 75 years old (incidence 12.5 higher) and female gender. CONCLUSIONS: Comparison of the incidence rates from spontaneous reports indicates a greater risk of hyponatremia for duloxetine for 2011-2013. This result needs to be confirmed by other studies. The advanced age and female sex are risk factors, irrespective of the molecule.

Post-SSRI Sexual Dysfunction: A Literature Review.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are a widely used class of drug. Post-SSRI sexual dysfunction (PSSD) is a condition in which patients continue to have sexual side effects after discontinuation of SSRI use. The prevalence of persistent sexual side effects after discontinuing SSRIs is unknown. The recognition and study of PSSD will increase our knowledge base of this underreported and distressing condition. AIM: To provide coverage of the current literature on PSSD, update information on the pathophysiology of PSSD, and discuss potential management options. METHODS: Comprehensive review of literature pertaining to PSSD. MAIN OUTCOME MEASURES: The symptoms, classification, pathophysiology, diagnostic considerations, and management of PSSD were reviewed. RESULTS: Common PSSD symptoms include genital anesthesia, pleasure-less or weak orgasm, decreased sex drive, erectile dysfunction, and premature ejaculation. Different theories have been proposed to explain the pathophysiology of PSSD: epigenetic gene expression theory, cytochrome actions, dopamine-serotonin interactions, proopiomelanocortin and melanocortin effects, serotonin neurotoxicity, downregulation of 5-hydroxytryptamine receptor 1A, and hormonal changes in the central and peripheral nervous systems. The diagnosis of PSSD is achieved by excluding all other etiologies of sexual dysfunction. Treating PSSD is challenging, and many strategies have been suggested and tried, including serotonergic antagonists and dopaminergic agonists. There is still no definitive treatment for PSSD. Low-power laser irradiation and phototherapy have shown some promising results. CONCLUSION: PSSD is a debilitating condition that adversely affects quality of life. Further studies are warranted to investigate the prevalence, pathophysiology, and treatment of PSSD. Bala A, Nguyen HMT, Hellstrom WJG. Post-SSRI Sexual Dysfunction: A Literature Review. Sex Med Rev 2018;6:29-34.