Serotonin Reuptake Inhibitors Research Articles

Mastering Ejaculation Challenges Through Comprehensive Strategies: A Case Report

Background This case report explores the successful management of psychogenic anejaculation in a 31-year-old poultry farmer. Despite an 8-year history of anejaculation during intercourse, the patient achieved ejaculation during masturbation. Initial pharmacological intervention with duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, provided partial success. To address persisting challenges, dual sex therapy and sensate focus therapy were introduced, based on the work of Masters and Johnson. The integrated approach proved effective, leading to successful ejaculation and the conception of the patient's wife. This case emphasizes the necessity of a comprehensive approach to psychological anejaculation, combining pharmacological and psychotherapeutic interventions for successful outcomes.

Prevalence of Antidepressant Prescriptions for Community-Dwelling Adults Diagnosed with Depressive Disorder in the UK: A Systematic Review.

The UK National Institute for Health and Care Excellence (NICE) guidance for the treatment of depression is widely followed and has international influence. According to these guidelines, antidepressant medications are recommended for moderate to severe depression. Nonetheless, antidepressants are increasingly prescribed, including for cases of subthreshold and mild depression. This may indicate that a proportion of depressed patients uses pharmacological interventions with unclear evidence-base, though other factors such as physical and mental health comorbidities need to be accounted for. This study aims to investigate the prevalence and trends of antidepressant prescriptions among community-dwelling adults diagnosed with depression according to NICE recommendations. We conducted a systematic review of PsycInfo, PubMed/MEDLINE, and Scopus databases. Observational studies reporting on the prevalence of antidepressant treatments in UK adults diagnosed with depression were sought. Fifteen studies were included. The prevalence of antidepressants for depression treatment ranged from 30.8 to 95% and mainly concerned selective serotonin reuptake inhibitors (SSRIs) among classes of antidepressant drugs. Little information about depression severity as well as comorbid conditions was reported. High prevalence rates of antidepressant drug use highlight the widespread adoption of pharmacological interventions, while also raising concerns about compliance with NICE guidelines. Careful assessment of depressive illness severity and comorbidities is needed to ensure the delivery of adequate care to people with depression. Systematic Review Registration Number (PROSPERO) CRD42023448152.

Sexual dysfunctions (SD) and selective serotonin reuptake inhibitors (SSRIs): from preclinical studies to intervention strategies

In the light of existing literature, we reviewed the causes, management and potential therapeutic benefits of SSRI (Selective serotonin reuptake inhibitor) agents regarding sexual functions. (SSRIs) are the most commonly used medications for the treatment of depression, based on their effectiveness and safety profile. Sexual dysfunctions (SD) caused by SSRIs are one of the most important reasons for discontinuation of treatment in both genders. Knowing the intervention strategies in patients who develop SD is pivotal for the proper management of sexual side effects and the treatment adherence of patients. The effects of SSRIs on sexual functions can also be used to treat certain disorders. SSRIs have a high success rate in the treatment of premature ejaculation and their off-label use for this purpose is widely recognized.

Exploring The Relationship Between SSRIs, Falls, Fractures, And Bone Mineral Density In Older Irish Adults: Results From The TUDA Study

Abstract Background Selective Serotonin Reuptake Inhibitors (SSRIs) are associated with an increased risk of falls and fractures, though the results from studies are inconsistent. SSRIs may cause a decline in bone mineral density (BMD), but this remains unclear. We aimed to explore the relationship between SSRI use and falls, fractures and BMD in older Irish adults. Methods Study participants were from a cross-sectional study of adults aged >60 years; Trinity Ulster University Department of Agriculture (TUDA) study. Falls and falls resulting in fracture in the preceding year were self-reported so participants with an MMSE < 24 were excluded. The relationship between SSRIs and falls and falls with fractures was explored in multivariate logistic regression adjusting for relevant covariates and medications: loop and thiazide diuretics, alpha and beta blockers, calcium channel blockers, ACE-inhibitors, benzodiazepines, opioids. In a subgroup with no prior diagnosis of osteoporosis or on medications for same, the relationship with SSRI's and BMD (as assessed with DXA) was explored. Results There were 4521 participants, 67.6% female, mean age 73.3 ± 8.1 years, 9.4% (n=427) using SSRIs. SSRI use predicted an increased risk of falls in the last year both before and after multivariate adjustment (OR 1.71, 1.37-2.14, p<0.001). In participants with falls (n=1448), those who had a fall with fracture versus a fall with no fracture were no more likely to be using SSRIs. In a subsample, (n=2178) no relationship was found between SSRI use and BMD at the hip, neck of femur or spine. Conclusion SSRIs use was associated with a 71% increased risk of falls though did not predict BMD or fractures. However, duration of SSRI use was not known and there was no prospective follow up. It remains unclear whether increased fracture risk in SSRI users found elsewhere is explained solely by falls risk.

Managing Menopause: The Evolving Role of Estrogens, Selective Serotonin Reuptake Inhibitors, and Phytoestrogens in Balancing Hormonal Fluctuations.

Menopause is characterized by the cessation of menstruation for 12 consecutive months. In this narrative review, we describe the transitional stages of menopause, clinical presentation, pharmacological management of symptoms, and effects on fluctuating hormone levels. To standardize the stages of menopause, the Stages of Reproductive Aging Workshop + 10 (STRAW+10) system was designed with five distinct categories corresponding to symptom presentation and numerical years. Common clinical presentations consist of vasomotor hot flashes, mood changes, decreased libido, osteoporosis, and genitourinary changes, all of which are associated with changes in hormone levels.Because hormones play a major role in the mechanism of menopause, hormone replacement therapy with estrogen, progesterone, or a combination is explored and shown to demonstrate symptom reduction in a large percentage of women. Nonhormonal treatment and alternative therapies are used to treat vasomotor symptoms if contraindications present to hormone therapy or for those who prefer fewer side effects. Thus, many women experience uncomfortable symptoms during menopause, some of which cause significant changes in quality of life. In this regard, understanding the pathophysiology, symptomatology, and current treatment options with side effect profiles allows for continued research and discovery of advanced therapy for treating symptoms to ameliorate discomfort and pain in menopausal women.

Boosting Serotonin Synthesis Is Not Sufficient to Improve Motor Coordination of Mecp2 Heterozygous Mouse Model of Rett Syndrome.

Motor deficit is a core symptom of Rett syndrome, a rare neurological disease caused in most cases by mutations of the methyl-CpG-binding protein2 (MECP2) gene. Serotonin reuptake inhibitors improve motor coordination in Mecp2 heterozygous (Het) mice and serotonin depletion prevented this effect. Here, we assess alterations in indole levels in various brain regions and whether boosting brain serotonin synthesis with the serotonin precursors tryptophan, 5-hydroxytryptophan and α-lactalbumin rescued motor coordination deficit of Mecp2 Het mice. Motor coordination was assessed in the accelerated rotarod during and after systemic administration of serotonin precursors for 2-3 weeks. Since no data are available, the effect of α-lactalbumin on tryptophan, serotonin and 5-hydroxyindoleacetic acid levels was evaluated in various brain regions in order to identify the dose of ALAC to evaluate on motor coordination. As compared to WT, Mecp2 Het mice show reduced levels of serotonin in the whole brain, hippocampus, brainstem and cerebral cortex, but not the striatum. Reduced levels of 5-hydroxyindoleacetic acid were observed in the hippocampus and brainstem. Doses of serotonin precursors increasing brain tryptophan and/or serotonin production and metabolism had no effect on motor coordination. The results indicate that boosting serotonin synthesis is not sufficient to improve motor coordination of Mecp2 Het mice.

Mental disorders after myocardial infarction: potential mediator role for chemokines in heart-brain interaction?

Acute myocardial infarction (MI) remains one of the leading causes of mortality and morbidity in the global communities. A prevailing topic that has attracted increasing attentions over the past few decades is the so-called heart-brain interaction, in particular following a major traumatic event such as MI. Increased prevalence of depression and other mental disorders has been recognized in cardiac patients after MI, coronary catheterization, or cardiothoracic surgeries. In this review, we focus on the potential pathogenic mechanisms and pre-clinical transcriptomic evidence for identifying potential mediators of post-MI depression. We first summarize the conventional mechanistic understanding that leads to the current clinical management of post-MI depression with the use of selective serotonin reuptake inhibitors (SSRIs) and cognitive behavior and exercise therapies. We further envisage a possible role played by certain chemokines, e.g., Chemokine (C-X-C motif) ligand 12 (CXCL12) and Chemokine (C-C motif) ligand 2 (CCL22), in serving as signaling molecules to connect the MI-induced heart damage to the pro-depressive changes in brain during the post-MI period. Future in-depth investigations into this chemokine hypothesis will be instrumental in developing new chemokine-targeted therapies for better management of the cardiac patients suffering from post-MI depression.

The Effectiveness of Ketamine Treatment on Depression

As the diagnosis rate of depression continues to rise, effective treatment options for this condition have become one of the most researched areas in the field. Earlier antidepressants were primarily developed based on mechanisms that involve regulating imbalanced neurotransmitters. For example, the widely known Selective Serotonin Reuptake Inhibitors (SSRIs) and various tricyclic antidepressants work by adjusting the concentration of different neurotransmitters, such as dopamine and norepinephrine, in the synaptic cleft to alleviate depressive symptoms. Additionally, many therapeutic approaches have been developed and applied based on the widely accepted hormone hypothesis and neurotrophic factor hypothesis. Ketamine, a drug traditionally used as an anesthetic, has recently been discovered to possess antidepressant properties. Its efficacy and underlying neuroscientific mechanisms are currently under investigation. Unlike earlier antidepressants, Ketamine produces significant antidepressant effects within a short time after administration. Multiple studies have suggested that Ketamine's rapid and effective therapeutic results may be based on entirely new antidepressant mechanisms and targets that have yet to be fully understood. This provides a new solution for the treatment of treatment-resistant depression and offers new hope to patients who have tried various treatments without success. In this literature review, Ketamine's therapeutic effects and its underlying mechanisms will be thoroughly examined. The content will be divided into three sections: significant antidepressant effects, underlying principles and mechanisms, and factors relevant to the improvement of Ketamine therapy.

Drug-Drug Interactions of Selective Serotonin Reuptake Inhibitors: A Pharmacovigilance Study on Real-World Evidence from the EudraVigilance Database.

As the most common psychiatric symptom, depression represents a subject of high interest for the medical community. Background/Objectives: International guidelines consider selective serotonin reuptake inhibitors (SSRIs) the first-line treatment of depression. Although having better efficacy and tolerability in comparison to tricyclic antidepressants or monoamine oxidase inhibitors, the diversity and potential severity of adverse effects and interactions manifested by SSRIs, combined with the frequency of prescriptions, lead to the necessity of evaluating real-world data. The aim of this study was to identify and evaluate the drug interactions reported in EudraVigilance (EV) for the six SSRIs representatives that are authorized in Europe: fluoxetine (FXT), fluvoxamine (FVM), citalopram (CIT), escitalopram (ESC), paroxetine (PAR) and sertraline (SER). The entire class of SSRIs was examined as a comparator to identify whether one of the representatives was more prone to reporting. Methods: Descriptive analysis and disproportionality analysis were conducted on data extracted from the EV database. Results: A total of 326,450 adverse reactions (ADRs) were reported for the SSRIs group. Approximately a quarter of these (n = 83,201; 25.46%) were reported for SER and 22.37% (n = 73,131) for PAR. Of the total ADRs reported, 2.12% (n = 6925) represent preferred terms related to drug-drug interactions (DDIs): SER (n = 1474; 22.37%), CIT (n = 1272, 19.86), and FXT (n = 1309, 19.83%). Specific ADRs related to inhibitory activity represent 0.98%, and for potentiating activity, 1.89%. Conclusions: Although representing a small value of the total ADRs, DDIs may be related to severe outcomes. Awareness should be raised for this category of ADRs that can be reduced by the joined efforts of physicians and pharmacists.

A Discrepancy in the Reports on Life Events Between Parents and Their Depressed Children Is Associated with Lower Responsiveness to SSRI Treatment.

Introduction: Exposure to a range of stressful life events (SLE) is implicated in youth psychopathology. Previous studies point to a discrepancy between parents'/children's reports regarding stressful life events. No study systematically assessed the correlation between such discrepancies and psychopathology in depressed youth. This study was designed to assess parent-youth discrepancies regarding stressful life events and its association with severity of psychopathology at baseline and response to selective serotonin reuptake inhibitor (SSRI) treatment in depressed youth. Methods: Reports regarding stressful life events were assessed in children/adolescents suffering from depressive/anxiety disorders using the life events checklist (LEC), a self-report questionnaire measuring the impact of negative life events (NLE) and positive life events (PLE), as reported by the children and their parents. The severity of depression/anxiety disorders and response to antidepressant treatment were evaluated and correlated with both measures of LEC. Results: Participants were 96 parent-child dyads (39 boys, 57 girls) aged 6-18 years (mean = 13.90 years, SD = 2.41). Parents reported more NLE and higher severity of NLE events than their children (number of NLE: 7.51 ± 4.17 vs. 6.04 ± 5.32; Cumulative severity of NLE: 24.95 ± 14.83 vs. 17.24 ± 12.94). Discrepancy in PLE, but not NLE, was associated with more severe psychopathology and reduced response to treatment. Discussion: Discrepancy in informant reports regarding life events in depressed/anxious youth, especially regarding PLE, is associated with more severe psychopathology and reduced response to pharmacotherapy. It is essential to use multiple reporters in assessing stressful life events in children.

Exploring the Neuropharmacological Terrain of Depression and Anxiety: Mechanisms, Therapies, and Future Avenues

Depression and anxiety are prevalent mental health illnesses that have significant worldwide consequences, impacting millions of individuals who experience chronic feelings of melancholy, excessive worry, and significant limitations in their everyday activities. Major Depressive Disorder (MDD) and several anxiety disorders, such as Generalized Anxiety Disorder (GAD), panic disorder, and social anxiety disorder, are defined by severe symptoms that make their treatment more difficult, especially when these illnesses happen at the same time. Gaining a comprehensive understanding of the neuropharmacological mechanisms that are responsible for these illnesses is of utmost importance in order to facilitate the development of treatments that are very effective. The existing therapy approaches, such as Selective Serotonin Reuptake Inhibitors (SSRIs) and newer antidepressants, provide partial relief but do not work for everyone. This suggests that further research is necessary to explore the underlying neurological causes of these illnesses. Recent developments in the field of neuropharmacology have provided insights into the significance of imbalances in neurotransmitters, specifically serotonin, norepinephrine, and dopamine, in the underlying mechanisms of mood disorders. Disruption of the Hypothalamic-Pituitary-Adrenal (HPA) axis and neuroinflammation are also major factors in the development of these illnesses. This review offers a thorough examination of these pathways, emphasizing the functions of neurotransmitter systems, neurostimulation treatments, and developing pharmaceutical medicines. This study investigates the possibility of new neuropharmacological targets, including NMDA receptor antagonists, AMPA receptor modulators, and neurosteroids, to enhance the effectiveness of treatment. In addition, it discusses non-pharmacological methods such as Cognitive Behavioral Therapy (CBT), physical activity, and mindfulness, highlighting their neuropharmacological foundations and advantages.This review is to provide an in-depth investigation of the current understanding and approaches to addressing depression and anxiety by including latest research findings. The text discusses crucial therapeutic approaches and presents potential areas of future study that could improve treatment results for these prevalent mental health illnesses.

Incidence of Idiosyncratic Drug-Induced Liver Injury Caused by Prescription Drugs.

The incidence of drug-induced liver injury (DILI) is not known for most prescription medications. We aimed to estimate the incidence of DILI for commonly prescribed outpatient drugs. To establish a baseline estimate of DILI incidence, we used the estimated incidence (EI) of amoxicillin/clavulanate DILI from a previous population-based study in Iceland. This was combined with the multicenter prospective DILI Network (DILIN) cohort and the US population-based Medical Expenditure Panel Survey (MEPS). From 2005 to 2019, prescription drugs with at least five bona fide DILIN cases and data from at least 10 of the 15years from MEPS during that timeframe were included. The EI for 'drug A' was calculated as follows: RESULTS: In total, 30 drugs met the inclusion criteria, of which 11 were antibiotics, 4 were antiepileptic drugs (AEDs), 4 were statins, and 11 were other drug types. The highest EI was seen with azathioprine and older AEDs, with one DILI case per 349-2329 new prescriptions. The EI of antibiotics ranged greatly, with the highest risk seen for minocycline, amoxicillin/clavulanate, and nitrofurantoin (approximately 1:1000-2400 new prescriptions), and lowest risk for clindamycin, doxycycline, azithromycin, and amoxicillin (approximately 1:40,000-170,000 new prescriptions). The EI for commonly prescribed statins was approximately 1:10,000-50,000. Important medication classes with > 5 million new prescriptions from 2005 to 2019 but fewer than five DILIN cases included β-blockers, thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, selective serotonin reuptake inhibitors, and metformin, which presumably have very low DILI incidence. The highest EI was found for azathioprine, older antiepileptics, and minocycline. In contrast, many widely used drugs are rare causes of DILI. These findings may help clinicians better weigh potential benefits of medications against hepatotoxicity risk.

The Impact of Antidepressants on COVID-19 and Post-Acute COVID-19 Syndrome: A Scoping-Review Update

On May 20, 2024, this systematic scoping review in PUBMED identified 1016 articles related to AD and COVID-19, Long COVID and SARS-COV-2. These included 10 retrospective "large scale" studies (> 20000 chart reviews), 8 prospective clinical trials (plus 4 regarding Long COVID), 11 placebo-controlled randomized (RCT) (plus 2 regarding Long COVID) and 15 meta-analyses. COVID-19: Retrospective studies with cohorts taking AD primarily for psychiatric comorbidities or chronic pain conditions directly prior to SARS-COV-2 infection described that this substance class (most studied: Selective Serotonin Re-Uptake Inhibitors (SSRI) and Selective Serotonin Noradrenaline Re-Uptake Inhibitors (SSNRI)) were associated with (i) significantly fewer SARS-COV-2 infections and (ii) a milder course of COVID-19 ("COVID-19 protection"). Ten of the 11 RCTs found regarding COVID-19 tested fluvoxamine, as this old AD appeared suitable as a prophylactic agent against severe COVID-19, taking into account its in vitro potency against the progression of intracellular sepsis cascades. Therefore, most (12 out of 15) meta-analyses also referred to fluvoxamine. They found (iii) a significant (40-70% reduction) in mortality, intubation and hospitalization rates when fluvoxamine was used as an add-on to standard therapy for mild to moderate COVID-19. When this AD was used in the early stages of the disease, it was more successful than when it was given later in advanced, severe COVID-19 (e.g. severe pneumonia, final sepsis stages). A dose dependency was observed: 2x50 mg fluvoxamine over 15 days was less effective than 2x100 or even 3x100 mg with an adverse event profile still at the placebo level. Direct comparisons with drugs approved for COVID-19 do not yet exist. A first indirect meta-analytical comparison showed an advantage of paxlovid or molnupiravir versus fluvoxamine against the development of severe COVID-19: risk reduction of 95% (I2 = N/A, but only one study) or 78% (I2=0) versus 5+-5% (I2=48). However, an add-on of fluvoxamine was still significantly more efficacious than symptom-oriented standard therapy alone. Long COVID: A common Long COVID phenotype with dominant anxiety and depression symptoms, which responds to AD, relaxation therapy and/or psychotherapy, has now been identified. Casuistics report positive effects of AD on fatigue, cognitive and autonomic dysfunctions. A first large prospective open-label RCT has just shown significantly more favourable courses, less viral load and less pro-inflammatory cytokines in the treatment of mild to moderate COVID-19 with fluvoxamine versus standard treatment, also with regard to the subsequent development of neuropsychiatric and pulmonary Long COVID or fatigue. Overall, there is promising evidence of a preventive effect of AD (especially fluvoxamine) against progression to severe COVID-19 and against the development of Long COVID. It is likely, that the entire AD substance class could be effective here. This assumption is based on the results of retrospective large scale studies, but awaits verification by better controlled studies. The potential effectiveness/efficacy (currently low and moderate confidence of the evidence for the entire substance class and specifically fluvoxamine, respectively) of fluvoxamine as an add-on against COVID-19 and possibly also directly against Long COVID could stimulate similar projects in other infectious diseases that also have the potential to pose a lasting threat to the health of those affected. We consider the evidence to date to be sufficient to be able to emphasize a possible positive effect of these substances in the psychoeducation of patients with COVID-19 or Long COVID who are already receiving AD for other conditions - especially also against the symptoms associated with the viral disease or its consequences. In regions where neither vaccines nor antiviral agents currently approved for the prevention or treatment of COVID-19 are available, AD and in particular fluvoxamine would be a cost-effective alternative to protect against a severe course, even if this AD appears to have a smaller effect against COVID-19 than the currently approved antiviral agents, but with presumably better tolerability. A direct comparative clinical trial with approved antiviral agents is still pending and should be positive to further open the door for a guideline-based recommendation of fluvoxamine (or perhaps even AD) for COVID-19 or its aftermath.

Clinical effects of CYP2D6 phenoconversion in patients with psychosis.

Pharmacogenetics is considered a promising avenue for improving treatment outcomes, yet evidence arguing for the use of pharmacogenetics in the treatment of psychotic disorders is mixed and clinical usefulness is under debate. Many patients with psychosis use multiple medications, which can alter the metabolic capacity of CYP enzymes, a process called phenoconversion. In clinical studies, treatment outcomes of drugs for psychosis management may have been influenced by phenoconversion. Here we evaluate the impact and predictive value of CYP2D6 phenoconversion in patients with psychotic disorders under pharmacological treatment. Phenoconversion-corrected phenotype was determined by accounting for inhibitor strength. Phenoconversion-corrected and genotype-predicted phenotypes were compared in association with side effects, subjective well-being and symptom severity. Phenoconversion led to a large increase in poor metabolizers (PMs; 17-82, 16% of sample), due to concomitant use of the serotonin reuptake inhibitors fluoxetine and paroxetine. Neither CYP2D6-predicted nor phenoconversion-corrected phenotype was robustly associated with outcome measures. Risperidone, however, was most affected by the CYP2D6 genotype. Polypharmacy and phenoconversion were prevalent and accounted for a significant increase in PMs. CYP2D6 may play a limited role in side effects, symptoms and well-being measures. However, due to the high frequency of occurrence, phenoconversion should be considered in future clinical trials.

The safety and efficacy of N-acetylcysteine as an augmentation in the treatment of obsessive-compulsive disorder in adults: a systematic review and meta-analysis of randomized clinical trials.

Obsessive-compulsive disorder (OCD) ranks as the fourth most prevalent psychiatric disorder, with selective serotonin reuptake inhibitors (SSRIs) as its mainstay pharmacological treatment. However, approximately 40 to 60% of patients do not adequately respond to initial treatment, highlighting the need for alternative options. N-acetylcysteine (NAC) is one of the several medications that have been used in augmentation with SSRIs to enhance their efficacy. We aimed to investigate the safety and efficacy of NAC, a glutamate-modulating agent, as an augmentation in the treatment of moderate to severe OCD. We conducted a thorough search across PubMed, Scopus, Web of science, and ProQuest to identify relevant trials published until December 2023. The primary outcome of interest was the mean difference between the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores before and after administrating augmented NAC among patients with moderate to severe OCD. Furthermore, we compared the occurrence of adverse drug events between the experimental and control groups. We included six randomized controlled trials with 195 patients. The results of our study indicated a positive outcome for the experimental group in terms of the total Y-BOCS score when using the medication for a period of five to eight weeks (p-Value = 0.05). However, no significant difference was observed for durations shorter than five weeks or longer than 12 weeks. Additionally, no significant difference was found between the two groups in terms of the obsession and compulsion Y-BOCS scores. Furthermore, no significant differences were observed in terms of adverse events. Augmentation of NAC with SSRIs may benefit patients with moderate to severe OCD. However, it is necessary to conduct additional multi-center trials over extended periods to develop a comprehensive strategy for action. https://www.crd.york.ac.uk/prospero/, identifier CRD42023463683.

Relationship between selective serotonin reuptake inhibitors and hypertension

Relationship between selective serotonin reuptake inhibitors and hypertension

The minimal important difference in obsessive-compulsive disorder: An analysis of double-blind SSRI trials in adults.

The change in symptoms necessary to be clinically relevant in obsessive-compulsive disorder (OCD) is currently unknown. In this study, we aimed to create an empirically validated threshold for clinical significance or minimal important difference (MID). We analyzed individual participant data from short-term, double-blind, placebo-controlled registration trials of selective serotonin reuptake inhibitors in adult OCD patients. Data were collected from baseline to week 12. We used equipercentile linking to equate changes in the Clinical Global Impression (CGI) scale to changes in the Yale-Brown Obsessive-Compulsive Scale (YBOCS). We defined the MID as the YBOCS change linked to a CGI improvement of 3 (defined as "minimal improvement"). We included 7 trials with a total of 1216 patients. The CGI-scores and YBOCS were moderately to highly correlated. The MID corresponded to 4.9 YBOCS points (95% CI 4.4-5.4) for the full sample, or a 24% YBOCS-decrease compared to baseline. The MID varied with baseline severity, being lower in the group with mild symptoms and higher in the group with severe symptoms. By linking the YBOCS to the CGI-I, this is the first study to propose an MID in OCD trials. Having a clearly defined MID can guide future clinical research and help interpretation of efficacy of existing interventions. Our results are clinician-based; however, there is further need for patient-reported outcomes as anchor to the YBOCS.

Selective Serotonin Reuptake Inhibitors and Solitary Rectal Ulcer Syndrome: A Bloody Relationship.

Solitary rectal ulcer syndrome (SURS) is a poorly understood and uncommon benign disorder of the lower gastrointestinal tract. It presents with various symptoms, often misinterpreted as inflammatory bowel disease. To date, there is no association between the use of selective serotonin reuptake inhibitors (SSRIs) and SURS. A 29-year-old male on paroxetine for six months and with a non-contributory surgical history presented to the clinic due to three months of haematochezia, abdominal pain and mucoid discharge. Physical examination and a review of systems were unremarkable; a colonoscopy demonstrated a suspicious ulcerated lesion in the rectum, which was identified as SURS on biopsy. The patient was advised lifestyle and dietary modifications. In addition, paroxetine was discontinued, and patient was switched to venlafaxine, a serotonin-norepinephrine reuptake inhibitor. Subsequently, the patient's symptoms resolved gradually, and he did not report any signs of recurrence on follow-up. Literature confirms that SSRIs can increase the occurrence of GI ulceration yet focuses specifically on upper gastrointestinal bleeding rather than rectal bleeding. This finding raises the need for further research. SURS is often underdiagnosed or misdiagnosed as inflammatory bowel disease.The pathophysiology and aetiology behind SURS remain obscure.This case points to a potential correlation between SSRIs use and SURS development.

Impact of ante-mortem fluoxetine administration on estimation of post-mortem interval and insect activity in rabbit carcasses

BackgroundIncreasing the number of drug-related deaths has affected medico-legal death investigations. Drugs within a corpse have a great impact on the insects’ development rate which in turn will affect the rate of post-mortem decomposition and the estimation of the post-mortem interval. This explains the importance of the application of forensic entomotoxicology, which studies the impact of drugs and toxins on the development and succession patterns of insects. The current study aimed to determine the impact of fluoxetine, one of the selective serotonin reuptake inhibitors (SSRIs), on post-mortem decomposition, insects’ attraction, and its pattern of succession on carcasses. Sixteen healthy male and female Oryctolagus cuniculus rabbits were chosen to be included in this study. They were divided into a treated group of eight rabbits received oral fluoxetine for 28 days and a control group of eight rabbits received oral distilled water for 28 days. After oral administration of 10 mg/kg/day of fluoxetine and distilled water for 28 days, rabbits were sacrificed, and carcasses were transmitted to the roof of Research and Training Centre on Vectors of Diseases at faculty of Sciences, Ain Shams University, for following up the post-mortem decomposition process and insect’s attraction to carcasses for 60 days. Carcasses were put in two outdoor sites that differ in temperature to assess the effect of temperature on decomposition process.ResultsFluoxetine administration has accelerated the rate of post-mortem decomposition in the treated carcasses by 3–9 days compared to the control ones and affected the numbers and species of attracted insects, while it had no effect on the insects’ succession patterns. Exposure of carcasses to direct sunlight has accelerated the rate of decomposition in comparison to that of carcasses put in shade in the overall period of decomposition by about 14 to 16 days.ConclusionsFluoxetine has an important and effective role in post-mortem decomposition and estimation of post-mortem interval (PMI) and has a great impact on attracted insects to the treated carcasses. Temperature has a great effect on the rate of decomposition of carcasses. Higher temperature accelerates the rate of post-mortem decomposition.

Personalized therapy and its side effects in patients with multiple sclerosis with depressive disorders

Depressive disorders in multiple sclerosis are the leading syndrome, but they have not been sufficiently studied. The clinical recommendations contain only a list of medications that were previously prescribed to patients with depression. To date, there is no description of the preferred groups of drugs for the treatment of depressive disorders, the starting dosage and timing of use, as well as possible adverse reactions when prescribing therapy to multiple sclerosis patients with depression. The purpose of this study is to search for optimal therapy for the relief of depressive disorders in patients with multiple sclerosis. Patients and methods: The study involved 203 patients with a confirmed diagnosis of multiple sclerosis (MS). The age of the patients at the time of examination ranged from 15 to 60 years, with the mean age of 39.7±10.91 years. Taking into account the type of course of the disease, MS patients were distributed as follows: 179 patients with relapsing remitting multiple sclerosis (RRMS) and 24 patients with secondary progressive multiple sclerosis (SPMS). The mean age of the examined patients with RRMS was 38±10 years; the duration of the disease was on average 8.23±6.57. The mean age of the onset of the disease was 30.2±10.5. The average disability index was EDSS 2.30±1.40. The age of the examined patients with SPMS was 46±9.00 years. The average age of onset of the disease was 33.33±8.02 years, and the level of disability was EDSS 5.70±0.30. All participants received multiple sclerosis disease modifying drugs (DMDs) and signed informed consent before being included in the study. The Beck's Depression Inventory was used to identify depression. The diagnosis of depressive disorder was established in accordance with the criteria of ICD-10 by a psychiatrist. Results and discussion: The choice of an antidepressant was made taking into account the type and degree of depression. Preference was given to the group of selective serotonin reuptake inhibitors (SSRIs), since MS patients poorly tolerate drugs with a strong sedative effect. Escitalopram was more often prescribed for anxiety depression, agomelatine for melancholic and hypochondriac depression, sertraline for asthenic depression, and fluvoxamine for adynamic depression. The starting dosage of the antidepressant in MS patients was almost twice as different from the dosage in the clinical recommendations for the treatment of depressive disorder. Due to the severity of neurological disorders, in a number of MS patients with the introduction of the starting dosage of an antidepressant, signs of sensitive ataxia, increased anxiety, and headaches were noted, therefore, the administration of an antidepressant was performed with slow titration. The association of side effects with periventricular foci in the frontal and parietal lobes of the brain has been revealed, which must be taken into account when prescribing therapy. Conclusion: Starting from the period of diagnosis of multiple sclerosis, patients need to be diagnosed for affective disorders, and risk factors that can cause depression need to be identified. When prescribing antidepressant therapy, it is necessary to take into account the type of depressive disorder, as well as the dosage of the drug, in order to exclude undesirable side effects.