Effects Of Selective Serotonin Reuptake Inhibitors Research Articles

Unraveling the Serotonergic Mechanism of Stress-Related Anxiety: Focus on Co-Treatment with Resveratrol and Selective Serotonin Reuptake Inhibitors

Background/Objectives: In post-traumatic stress disorder (PTSD), anxiety-like symptoms are often associated with elevated noradrenaline levels and decreased serotonin. Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat anxiety, but elevated serotonin has been observed in some anxiety disorders. This study investigates stress-induced anxiety as an immediate effect of chronic stress exposure using the predator stress paradigm. Methods: We examined serotonin levels, serotonin transporter (SERT), and 5-HT3A receptor gene expression in response to stress. The effects of SSRIs (paroxetine, sertraline) and resveratrol on these parameters were also analyzed, alongside co-treatment with resveratrol and sertraline. Results: Chronic stress exposure led to a significant increase in serotonin levels and upregulation of SERT and 5-HT3A receptor expression. SSRIs failed to prevent anxiety or reduce serotonin levels, partly due to suppressed SERT expression. Resveratrol downregulated SERT and 5-HT3A expression less than SSRIs but effectively reduced anxiety and restored serotonin, likely by upregulating MAO-A expression. Co-treatment with resveratrol and sertraline produced the strongest anxiolytic effect. Conclusions: Elevated serotonin and increased expression of SERT and 5-HT3A receptor genes are key factors in stress-related anxiety. Resveratrol and SSRIs target these mechanisms, suggesting potential therapeutic strategies for anxiety disorders. Future research will focus on further elucidating the serotonergic mechanisms involved and identifying new anxiolytic drug targets.

The Effects of SSRIs and Antipsychotics on Long COVID Development in a Large Veteran Population

The development of Long COVID is a complex disease process that may be partially driven by neuroinflammation. Antipsychotics have been shown to exert neuroprotective effects under certain conditions. Our study aimed to determine if veterans treated with antipsychotics and/or selective serotonin reuptake inhibitors (SSRIs) for a psychiatric condition had a reduced risk of developing long-term COVID. We conducted a retrospective cohort study with two cohorts of patients based on the COVID-19 wave in which the patient’s initial infection occurred (Cohort 1: alpha/beta waves, and Cohort 2: delta/omicron waves) with stratification by age. A multivariate logistic regression model was used to evaluate the association between the use of antipsychotics and Long COVID diagnosis. In Cohort 1, antipsychotic use was associated with 43% and 34% reductions in the odds of developing Long COVID in patients aged <65 and >65 years, respectively. This association was reduced in the second cohort to 11% in patients aged <65 years and without an association over 65 years of age. SSRIs showed no benefit in either age group or cohort. Our results show that antipsychotic use for the treatment of a mental health condition was associated with a reduction in the risk of developing Long COVID, and the magnitude of this reduction varied between COVID-19 cohorts.

Effects of selective serotonin reuptake inhibitors on platelet functions: a literature review.

Many epidemiological studies have evidenced an increased bleeding risk associated with selective serotonin reuptake inhibitors (SSRIs), yet the underlying mechanisms remain unclear. This review summarizes data on SSRIs' effects on platelet functions assessed with assays used in clinical practice and highlights the areas that deserve further investigation. Conflicting results of SSRI effects on platelet aggregation were observed irrespectively of the agonist used, the antidepressant drug or the study type. Alike, discrepant results were reported with flow-cytometry-based assays assessing either platelet surface glycoprotein levels, integrin activation, agonist-induced secretion of intraplatelet granule content or membrane anionic phospholipid exposure. Other tests may have detected a platelet function defect in SSRIs samples, however, results were largely inconsistent. Critical literature examination unveils very low certainty of evidence on potential SSRI effect on platelet functions. Findings are often inconsistent even when similar methods are used, most likely because of differences in study design, included patients (age, comorbid conditions), SSRIs' type and dose, uncontrolled confounding factors, and statistical analysis power. Further studies are needed to disentangle any intrinsic antiplatelet effect of SSRIs and the multiple confounding factors, mainly the depression control itself and the degree of platelet SERT inhibition.

8429 Serotonin Receptor Antagonist Alleviates Vascular Defects Produced by Selective Serotonin Reuptake Inhibitor Treatment During Gestation

Abstract Disclosure: L.P. Agnew: None. R. Domingues: None. A. Weichmann: None. L.L. Hernandez: None. Maternal mental health is critical for both mother and infant and often antidepressant therapy outweighs the potential risks of selective serotonin reuptake inhibitor (SSRI) treatment; however, SSRI use is associated with adverse neonatal outcomes. Preliminary work in our laboratory revealed placental apoptosis in pregnant dams treated with fluoxetine (FLX) and dams genetically deficient for the serotonin transporter gene. We hypothesize that SSRIs decrease placental blood flow, causing apoptosis and organ death via signaling through the serotonin 2A/2C receptors. Pregnant female C57BL6 mice were randomized to be treated daily, via I.P. injection, from E10-17.5 with saline (CON; n=6), 2 mg/kg FLX (n=5), or 2 mg/kg ketanserin plus 2 mg/kg FLX (n=5). On E17.5, using high-resolution ultrasound imaging, we identified the uterine artery, individual umbilical cords, and placental disc blood vessels. We calculated blood pressure, blood volume, blood flow rate, and heart rate in the uterine artery, umbilical cord, and placental disc. FLX (decreased blood volume in the uterine artery compared to ketanserin plus FLX (48.42 ± 18.26, 116.54 ± 45.25; p=0.0077), and decreased average (89.38 ± 31.50) and peak (130.36 ± 39.05) blood velocity in the uterine artery compared to ketanserin plus FLX average (162.76 ± 68.46; p=0.0322) and peak (236.77 ± 92.43; p=0.0242) blood velocity. FLX decreased average (0.04 + 0.02) and peak (0.07 ± 0.04) blood pressure in the uterine artery compared to ketanserin and FLX treated animals average (0.12 ± 0.10; p=0.0634) and peak (0.25 ± 0.19; p=0.0412) blood pressure. Ketanserin plus FLX (391 ± 38.29) decreased heart rate (BPM) in the placental disc compared to untreated controls (450.67 ± 26.08; p=0.0128). In the umbilical cord, ketanserin plus FLX (393 ± 28.25) decreased BPM compared to CON (450.17 ± 29.44; p=0.0078) and compared to FLX treatment alone (437.20 ± 17.28; p=0.0450). FLX treatment of dams during pregnancy reduces blood flow volume, heart rate, and blood flow velocity to the placenta via the uterine artery. The use of ketanserin, an inhibitor of serotonin receptor 2A/2C signaling, in combination with FLX, reduced the effects of FLX on the uterine artery. These data suggest that treatment with ketanserin could be utilized to alleviate the reproductive side effects of antidepressant usage for pregnant mothers while allowing the mother to remain on antidepressants. Future research should further investigate the effects of SSRI and ketanserin on blood flow to the fetus through the umbilical cord. Presentation: 6/2/2024

8429 Serotonin Receptor Antagonist Alleviates Vascular Defects Produced by Selective Serotonin Reuptake Inhibitor Treatment During Gestation

Abstract Disclosure: L.P. Agnew: None. R. Domingues: None. A. Weichmann: None. L.L. Hernandez: None. Maternal mental health is critical for both mother and infant and often antidepressant therapy outweighs the potential risks of selective serotonin reuptake inhibitor (SSRI) treatment; however, SSRI use is associated with adverse neonatal outcomes. Preliminary work in our laboratory revealed placental apoptosis in pregnant dams treated with fluoxetine (FLX) and dams genetically deficient for the serotonin transporter gene. We hypothesize that SSRIs decrease placental blood flow, causing apoptosis and organ death via signaling through the serotonin 2A/2C receptors. Pregnant female C57BL6 mice were randomized to be treated daily, via I.P. injection, from E10-17.5 with saline (CON; n=6), 2 mg/kg FLX (n=5), or 2 mg/kg ketanserin plus 2 mg/kg FLX (n=5). On E17.5, using high-resolution ultrasound imaging, we identified the uterine artery, individual umbilical cords, and placental disc blood vessels. We calculated blood pressure, blood volume, blood flow rate, and heart rate in the uterine artery, umbilical cord, and placental disc. FLX (decreased blood volume in the uterine artery compared to ketanserin plus FLX (48.42 ± 18.26, 116.54 ± 45.25; p=0.0077), and decreased average (89.38 ± 31.50) and peak (130.36 ± 39.05) blood velocity in the uterine artery compared to ketanserin plus FLX average (162.76 ± 68.46; p=0.0322) and peak (236.77 ± 92.43; p=0.0242) blood velocity. FLX decreased average (0.04 + 0.02) and peak (0.07 ± 0.04) blood pressure in the uterine artery compared to ketanserin and FLX treated animals average (0.12 ± 0.10; p=0.0634) and peak (0.25 ± 0.19; p=0.0412) blood pressure. Ketanserin plus FLX (391 ± 38.29) decreased heart rate (BPM) in the placental disc compared to untreated controls (450.67 ± 26.08; p=0.0128). In the umbilical cord, ketanserin plus FLX (393 ± 28.25) decreased BPM compared to CON (450.17 ± 29.44; p=0.0078) and compared to FLX treatment alone (437.20 ± 17.28; p=0.0450). FLX treatment of dams during pregnancy reduces blood flow volume, heart rate, and blood flow velocity to the placenta via the uterine artery. The use of ketanserin, an inhibitor of serotonin receptor 2A/2C signaling, in combination with FLX, reduced the effects of FLX on the uterine artery. These data suggest that treatment with ketanserin could be utilized to alleviate the reproductive side effects of antidepressant usage for pregnant mothers while allowing the mother to remain on antidepressants. Future research should further investigate the effects of SSRI and ketanserin on blood flow to the fetus through the umbilical cord. Presentation: 6/2/2024

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.

Comparing Selective Serotonin Reuptake Inhibitors (SSRIs) Alone and in Combination With Beta-Blockers for Treating Panic Disorders: A Prospective Cohort Study.

Background Panic disorders are prevalent psychiatric conditions affecting 1.6% to 2.2% of the global population. While selective serotonin reuptake inhibitors (SSRIs) are the first line of treatment, their initial exacerbation of symptoms presents challenges. Beta-blockers have shown promise in managing panic symptoms, but research comparing the efficacy of combined SSRI and beta-blocker therapy to SSRI monotherapy is limited, particularly in Saudi Arabia. Objective To assess the effectiveness of SSRIs combined with beta-blockers vs. SSRI monotherapy in improving panic disorder symptoms severity in patients at King Abdul-Aziz Hospital, Makkah, Saudi Arabia. Methods This prospective cohort study included 62 patients with panic disorder, divided into two groups: SSRI monotherapy (n=29) and SSRIs with beta-blockers (n=33). Panic disorder severity was assessed using the Panic Disorder Severity Scale (PDSS) after three months of treatment. Secondary outcomes included depression and anxiety symptoms, measured by the Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder Scale (GAD-7), respectively.Statistical analysis involved Mann-Whitney U tests for comparing PDSS scores between the groups due to non-parametric distributionand Chi-square tests for categorical variables. Relative risks (RR) were calculated to assess the likelihood of abnormal PDSS, PHQ-9, and GAD-7 scores between the groups. Multivariable linear regression was used to adjust for potential confounding factors. Results No statistically significant difference in PDSS scores was found between SSRI monotherapy (median=6,interquartile range (IQR)=3-9) and combination therapy (median=8, IQR=3-13) groups (p=0.188). The relative risk of abnormal PDSS scores was 1.8 times higher in the combination therapy group (p=0.077). No significant differences in depression (p=0.386) or anxiety (p=0.182) symptoms were observed. Additionally, 66.7% of combination therapy patients had abnormal PDSS scores compared to 33.3% in the SSRI group. The mean PHQ-9 score was 11.08±6.93, and the mean GAD-7 score was 10.69±6.41 for the total sample. Conclusion This study found no significant difference in the effectiveness of SSRIs combined with beta-blockers vs. SSRI monotherapy for treating panic disorders. However, the trend towards higher PDSS scores in the combination therapy group suggests further investigation is needed. Study limitations included small sample size, single-center design, short follow-up period, and lack of randomization. Despite these, the study provided valuable insights into treatment approaches for panic disorders in the Saudi population. Larger, randomized controlled trials with longer follow-up periods and multi-center designs are recommended for future research.

Effects of selective serotonin reuptake inhibitors on endocrine system (Review).

Selective serotonin reuptake inhibitors (SSRIs) are typically prescribed for treating major depressive disorder (MDD) due to their high efficacy. These drugs function by inhibiting the reuptake of serotonin [also termed 5-hydroxytryptamine (5-HT)], which raises the levels of 5-HT in the synaptic cleft, leading to prolonged activation of postsynaptic 5-HT receptors. Despite the therapeutic benefits of SSRIs, this mechanism of action also disturbs the neuroendocrine response. Hypothalamic-pituitary-adrenal (HPA) axis activity is strongly linked to both MDD and the response to antidepressants, owing to the intricate interplay within the serotonergic system, which regulates feeding, water intake, sexual drive, reproduction and circadian rhythms. The aim of the present review was to provide up-to-date evidence for the proposed effects of SSRIs, such as fluoxetine, citalopram, escitalopram, paroxetine, sertraline and fluvoxamine, on the endocrine system. For this purpose, the literature related to the effects of SSRIs on the endocrine system was searched using the PubMed database. According to the available literature, SSRIs may have an adverse effect on glucose metabolism, sexual function and fertility by dysregulating the function of the HPA axis, pancreas and gonads. Therefore, considering that SSRIs are often prescribed for extended periods, it is crucial to monitor the patient closely with particular attention to the function of the endocrine system.

Fluoxetine, but not paroxetine, alters the jaw-closing muscle activity during non-rapid eye movement sleep in mice

Sleep bruxism is an involuntary, exaggerated jaw-closing activity during sleep. Selective serotonin reuptake inhibitor (SSRI) use is a risk factor for bruxism. However, the effect of various SSRIs on masseter (jaw-closing) muscle activity remains unclear. Here, we examined the effects of long-term administration of two SSRIs, fluoxetine (FLX) and paroxetine (PRX), for 14 days on masseter muscle activity during wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep for 24 h in mice. Vigilance states were scored based on electroencephalographic, electrooculography and neck electromyographic (EMG) activities. The EMG activity of the masseter muscle was quantified in 6 h periods. FLX and PRX did not affect the duration of the three vigilance states. Both drugs significantly prolonged the REM sleep episode duration while decreasing the number of episodes. FLX significantly increased REM sleep onset latency. Neither FLX nor PRX affected the mean masseter EMG activity during wakefulness. FLX significantly increased the relative time of masseter muscle activity in NREM sleep during 02:00–08:00 and 08:00–14:00, while PRX did not affect three vigilance states. Overall, FLX had a limited but significant effect on masseter muscle activity in NREM sleep during specific periods.

Incidence of Hematoma Following Breast Reduction in Patients Taking Selective Serotonin Reuptake Inhibitor or Serotonin-Norepinephrine Reuptake Inhibitor: A Retrospective Review.

Background Selective serotonin reuptake inhibitor (SSRI) and serotonin-norepinephrine reuptake inhibitor (SNRI) use is more common in the plastic surgery population compared to the general population. This study was designed to assess the theoretical effect of SSRIs and SNRIs on platelet function and the potential for increased bleeding risk. This study sought to establish the incidence of postoperative bleeding following routine bilateral breast reduction for patients on SSRIs or SNRIs. The outcomes of this study contribute to the discussion of whether these medications should be discontinued before elective surgery. Methodology A retrospective chart review of all patients who received bilateral breast reduction surgery over a 10-year period was performed. Patient charts were reviewed for postoperative hematoma formation as well as medications being used around the time of surgery. The rate of hematoma formation in patients actively taking SSRIs or SNRIs at the time of surgery was compared with the rest of the study population. Results A total of 1,022 patients met the inclusion criteria for the study. The overall incidence of postoperative hematoma was 7.7%. Of these, 1.9% of patients had clinically significant hematomas that required operative evacuation, and the remaining were treated conservatively. The only variable associated with a significantly higher risk of hematoma formation was advanced age (p = 0.005). Conclusions There was no significant difference in hematoma incidence after breast reduction in patients taking SNRIs or SSRIs compared with the general population. This contradicts some of the previously published literature and can hopefully guide clinicians in counseling their patients preoperatively.

Selective Serotonin Reuptake Inhibitors for the Treatment of Depression in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Although selective serotonin reuptake inhibitors (SSRIs)are usually considered safe to use in patients with Parkinson's disease (PD), there are mixed data about their effectiveness, and only a few investigations have led to a total improvement of depressive symptoms in patients with PD. We aimed to conduct a comprehensive systematic review and meta-analysis of all studies that investigated the effectiveness of SSRIs in treating depression in the context of PD. From its commencement to June 2024, the databases of MEDLINE via PubMed, Scopus, Embase, and Google Scholar were electronically searched for the relevant papers. All full-text journal articles assessing the effectiveness of SSRIs in treating depression in patients with PD were included. The tool developed by the Cochrane Collaboration was utilized to evaluate the bias risk. Data were analyzed utilizing a pair-wise comparison meta-analysis using the standardized mean difference. A total of 19 articles and 22 separate interventions were included. We found that SSRI treatment attenuated depression in patients with PD (1.242 standardized mean difference, 95% confidence interval 0.956, 1.529, p < 0.001). The general heterogeneity of the studies was medium (ϰ2 = 72.818, T2 = 0.317, df = 21, I2 = 71.15%, p < 0.001). The funnel plot was reasonably symmetrical. However, three studies were trimmed to the left of the mean. Begg's test (p = 0.080), Egger's test (p = 0.121), and funnel plot showed no significant risk of publication bias. The meta-regression showed that the treatment effect increased as a function of paroxetine treatment duration (slope p = 0.001) but decreased as a function of sertraline treatment duration (slope p = 0.019). There are few controlled antidepressant trials on the PD population, even though patients with PD frequently experience depression and use antidepressants. Clinical studies that are larger and better structured are needed in the future to determine if antidepressants are useful for treating patients with PD with depression.

A Comprehensive Review of Analytical Methods Developed for Selective Serotonin Reuptake Inhibitors (SSRIs)

: Selective Serotonin Reuptake Inhibitors (SSRIs) are a key development in psychological pharmacology and treatment. It has been demonstrated that serotonin (5-HT) has a pharmacological role in a variety of anxiety- and mood-related conditions. Fluvoxamine, citalopram, escitalopram, paroxetine, sertraline, and fluoxetine are the six primary SSRIs now available in the United States for the treatment of depression and anxiety or mood-related disorders. Despite having a different chemical structure, these compounds function in an analogous fashion. The main mechanism by which SSRIs work is by preventing serotonin from being reabsorbed presynaptically at the serotonin transporter, which raises serotonin at the postsynaptic membrane, which is found in the serotonergic synapse. In order to ensure the effectiveness, safety, and quality control of SSRIs in pharmaceutical formulations, it is crucial to quantify them precisely. The present article provides an overview of the main analytical techniques developed to evaluate SSRIs in different matrices. It covers both conventional and hyphenated approaches and concentrates on the analytical methodologies developed to quantify SSRIs. It offers a general overview of the methods that have been developed and standardized for the evaluation of SSRIs in drug formulations and various matrices. It focuses on the major components of SSRI analysis, such as the solvents used for analysis, chromatographic column selections, detection wavelength, and validation parameters. It also discusses various validation parameters, such as accuracy, precision, retention duration, maximum absorbance wavelength (λmax), range, limit of detection (LOD), and limit of quantitation (LOQ).

SSRI Induced Sleep Bruxism and Jaw Muscle Dystonia- Management with Low Dose Quetiapine Along with Occlusal Guards (D9944, D9945)- Two Case Reports

Background: Long term use of SSRIs (selective serotonin re uptake inhibitors) sometimes induces a problem called nocturnal or sleep bruxism which is nothing but uncoordinated jaw muscle movements which leads to grinding and clenching of teeth. The undesired effect of SSRIs produces a muscle stiffness, jaw and neck muscle tenderness, continuous toothache, hypersensitivity, tooth fracture and TMJ pain. Different treatment modalities are there to manage this kind of problem without hampering the psychiatric prognosis of the patient. Here two cases of SSRI induced sleep bruxism along with successful managements are discussed which will throw some light to the potential treatment approaches of such rare disorders.

Evidence of the Immunomodulatory Effects of Selective Serotonin Reuptake Inhibitors in Patients With Depression Through a Systematic Review.

Depression is a common illness, affecting >264 million people worldwide. According to the literature, depression patients have baseline subclinical inflammation. The immunomodulatory effects of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), are largely unclear and poorly understood. Using evidence-based medicine, this study aimed to determine the immunomodulatory effects of SSRIs by assessing changes in immunomodulatory markers following SSRI treatment. Using the PubMed website, a literature search was conducted with various terminologies related to the treatment of depression and various markers of inflammation. Out of 387 retrieved articles, after critical appraisal and screening based on inclusion and exclusion criteria, 17 were selected. Qualitative synthesis and quantitative analysis were carried out. RevMan 5 software was used to synthesize and evaluate the data. Microsoft Word and Excel (Microsoft Corporation, Redmond, Washington, United States) were used for generating tables and figures. We extracted data from a total of 839 patients in 17 studies. A highly significant reduction in interleukins-6 (IL-6) (standardised mean difference (SMD) = 1.32 (95% confidence interval (CI): 0.58, 2.06), Z = 3.48, P = 0.0005), a significant reduction in tumor necrosis factor-alpha (TNF-α) (SMD = 1.29 (95% CI: 0.19, 2.39), Z = 2.30, P = 0.02) but no change in overall C-reactive protein (CRP) (SMD = 0.40 (95% CI: -0.26, 1.07), Z = 1.19, P = 0.23) levels were observed by using the random-effects model. There was substantial heterogeneity found between the studies. SSRIs have an immunomodulatory effect in patients with depression by significantly reducing the peripheral pro-inflammatory cytokine markers of IL-6 and TNF-α, which may contribute to ameliorating the response to antidepressant drug treatment. In contrast, no effects of SSRIs on acute-phase protein CRP were found.

ADHD medication adherence reduces risk of committing minor offenses in adolescents.

This study aimed to investigate the association between adolescents' adherence to attention-deficit/hyperactivity disorder (ADHD) medication and their risk of committing minor offenses. Using two Dutch databases, Statistics Netherlands (CBS) and the Foundation for Pharmaceutical Statistics (SFK), we aimed to investigate the association between adherence to ADHD medication and registered minor offenses between 2005 and 2019 of 18,234 adolescents (12-18 years). We used Cox regression analyses to compare the rate of committing minor offenses of adolescents during periods of high ADHD medication adherence compared to periods of low adherence (i.e., periods with or without sufficient amounts of dispensed medication). We additionally tested associations with adherence to selective serotonin reuptake inhibitors (SSRIs) as control medication and analyzed potential reverse causation. High ADHD medication adherence was associated with a reduced risk of committing a minor offense of between 33% and 38% compared to low adherence periods of ≥3 months (hazard ratio [HR] 0.67, confidence interval [CI] 0.64-0.71) or ≥6 months (HR 0.62, CI 0.59-0.65). The reduction in risk can likely be attributed to ADHD medication, given the absence of effects of SSRIs and no reverse causation. The reduction rate remained between 16% and 55% per sex, stimulant versus non-stimulant medication, different offense categories and further sensitivity analyses. Among adolescents using ADHD medication, rates of criminality were lower during periods of high medication adherence, suggesting that adherence to ADHD medication may contribute to prevention of minor offenses in adolescents.

Evaluation of selective-serotonin reuptake inhibitors and anti-androgens to manage sexual compulsivity in individuals serving a custodial sentence for a sexual offence

ABSTRACT The UK prison system offers a medical treatment pathway for people suffering from problematic sexual arousal (PSA) who have committed a sexual offence(s). The two main medications are Anti-androgens (AAs) and Selective-Serotonin Reuptake Inhibitors (SSRIs). Currently, evidence of the effectiveness of SSRIs is not sufficiently robust for them to be licensed in the UK for that purpose. Instead, SSRIs are prescribed ‘off-label’, and physicians must adhere to additional obligations in prescribing them. Yet SSRIs have fewer side effects than AAs and may be a better treatment option for many patients. The present study examined the effectiveness of AAs and SSRIs in incarcerated individuals with PSA (n = 77); the unmedicated comparison group (n = 58) resided at the same prison which houses people convicted of a sexual offence. Both medicated groups demonstrated reduced levels of PSA 3 months post-baseline; the comparison group did not. The findings provide evidence for the effectiveness of SSRIs in reducing PSA. The authors argue a randomised control trial is required to underpin the use of SSRIs in treating PSA and (potentially) its subsequent licensing. The latter would enable wider prescription in prison and community and make a substantive contribution to the prevention of sexual abuse.

The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial.

Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety. Participants (N = 655) performed an affective Go/NoGo task three times during the trial and computational models were used to infer reinforcement learning processes. There was poor task performance: only 54% of the task runs were informative, with more informative task runs in the placebo than in the active group. There was no evidence for the preregistered hypothesis that Pavlovian inhibition was affected by sertraline. Exploratory analyses revealed that in the sertraline group, early increases in Pavlovian inhibition were associated with improvements in depression after 12 weeks. Furthermore, sertraline increased how fast participants learned from losses and faster learning from losses was associated with more severe generalized anxiety symptoms. The study findings indicate a relationship between aversive reinforcement learning mechanisms and aspects of depression, anxiety, and SSRI treatment, but these relationships did not align with the initial hypotheses. Poor task performance limits the interpretability and likely generalizability of the findings, and highlights the critical importance of developing acceptable and reliable tasks for use in clinical studies. This article presents research supported by NIHR Program Grants for Applied Research (RP-PG-0610-10048), the NIHR BRC, and UCL, with additional support from IMPRS COMP2PSYCH (JM, QH) and a Wellcome Trust grant (QH).

Effects of selective serotonin reuptake inhibitors (SSRIs) on suicide: A network meta-analysis of double-blind randomized trials

The relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and suicide risk in patients with mental disorders remains controversial. We conducted a network meta-analysis to examine the effects of SSRIs on suicide risk in patients with mental disorders. A comprehensive search was conducted across PubMed, Web of Science, PsycINFO, CENTRAL, Wanfang Database, and China National Knowledge Infrastructure for articles published until December 19, 2023. The main outcomes were suicidal ideation and instances of suicidal behavior. We included 29 double-blind randomized trials in our analysis. The findings suggest that SSRIs primarily offer short-term protection against suicidal ideation. By week 2, paroxetine, fluoxetine, escitalopram, and non-SSRI treatments were linked to a decreased suicide risk compared with a placebo, with the exception of sertraline. This protective effect was diminished by week 8. In contrast, studies on instances of suicidal behavior from weeks 1 to 10 found no significant difference in efficacy between SSRIs, non-SSRIs, and placebo. These results indicate that SSRIs may offer short-term protection against suicidal ideation. However, their long-term effectiveness in mitigating suicidal ideation and preventing suicidal behaviors is limited.

An Examination of the Effectiveness of SSRIs with clomipramine on OCD Patients

Most psychiatrists begin pharmacotherapy for Obsessive Compulsive Disorder (OCD) treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) because they tend to lead to fewer side effects than other symptom-alleviating medications such as clomipramine. SSRIs have been shown to produce response rates of up to 60% in patients with OCD (Paxos, 2022). However, this leaves a considerable number of patients in need of other treatments. clomipramine may be used as either a monotherapy or in combination with an SSRI, as evidence has highlighted the positive impact it has on patients with OCD (Andrade, 2013). Previous research shows that clomipramine and SSRIs are roughly equivalent in benefit when taken alone (Mago, 2017). That said, less is known about the combination of these two medicines. This review will examine the literature comparing individuals with OCD medicated by either SSRIs or clomipramine alone, as well as those taking both in tandem in order to see which prescription best augments exposure and response prevention-based treatment. In addition, this review will briefly describe alternate treatments to examine other possible approaches to effective psychopharmacology.

Microdosing ketamine in Drosophila does not block serotonin reuptake, but causes complex behavioral changes mediated by glutamate and serotonin receptors.

Microdosing ketamine is a novel antidepressant for treatment-resistant depression. Traditional antidepressants, like selective serotonin reuptake inhibitors (SSRIs), inhibit serotonin reuptake, but it is not clear if ketamine shows a similar mechanism. Here, we tested the effects of feeding ketamine and SSRIs to Drosophila melanogaster larvae, which has a similar serotonin system to mammals and is a good model to track depressive behaviors, such as locomotion and feeding. Fast-scan cyclic voltammetry (FSCV) was used to measure optogenetically stimulated serotonin changes, and locomotion tracking software and blue dye feeding to monitor behavior. We fed larvae various doses (1-100 mM) of antidepressants for 24 h and found that 1 mM ketamine did not affect serotonin, but increased locomotion and feeding. Low doses (≤10 mM) of escitalopram and fluoxetine inhibited dSERT and also increased feeding and locomotion behaviors. At 100 mM, ketamine inhibited dSERT and increased serotonin concentrations, but decreased locomotion and feeding because of its anesthetic properties. Since microdosing ketamine causes behavioral effects, we further investigated behavioral changes with a SERT16 mutant and low doses of other NMDA receptor antagonists and 5-HT1A and 2 agonists. Feeding and locomotion changes were similar to ketamine in the mutant, and we found NMDA receptor antagonism increased feeding, while serotonin receptor agonism increased locomotion, which could explain these effects with ketamine. Ultimately, this work shows that Drosophila is a good model to discern antidepressant mechanisms, and that ketamine does not work on dSERT like SSRIs, but effects behavior with other mechanisms that should be investigated further.