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Introduction: Despite advances in obstetric care, postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Prior reviews of studies published through 2016 suggest an association of antidepressant use during late pregnancy and increased risk of PPH. However, a causal link between prenatal antidepressants and PPH remains controversial. Objectives: This systematic literature review aimed to synthesize the empirical evidence on the association of antidepressant exposure in late pregnancy with the risk of PPH, including studies published before and after 2016. Methods: A systematic literature search was conducted using PubMed, OVID Medline, EMBASE, SCOPUS, PsycINFO, and CINAHL from inception to September 9, 2023. Original, peer-reviewed studies (published in English) that reported on the frequency or risk of PPH in women with evidence of antidepressant use during pregnancy and included at least one control group were included. Results: Twenty studies (eight published after 2016) met inclusion criteria, most of which focused on the risks of PPH associated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). The main findings from the individual studies were mixed, but the majority documented statistically significant associations of PPH with late prenatal exposure, especially for exposures occurring within 30 days of delivery, compared with unexposed deliveries. Fourteen studies addressed underlying antidepressant indications or their correlates. Few studies focused on prenatal antidepressants and the risk of well-defined severe PPH or on antidepressant dose changes and general PPH risk. None examined competing risks of antidepressant discontinuation on mental health outcomes. Conclusions: Late pregnancy exposure to antidepressants may be a minor risk factor for PPH, but it is unclear to what extent reported associations are causal in nature, as opposed to correlational (effects related to nonpharmacological factors including maternal indication). For patients needing antidepressants during pregnancy, current evidence does not favor routinely discontinuing antidepressants specifically to reduce the risk of PPH. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common malignancy in women worldwide. Depression is a common psychological issue among these patients as they experience significant stress, and it impacts their quality of life. In this regard, the efficacy of antidepressants in depression for breast cancer is not studied. Objective: The objective of the study was to study the efficacy of antidepressants in the management of depression in breast cancer. Methods: Our databases included PubMed, MEDLINE, PsycINFO, Cochrane, Scopus, and Gray literature published in English. Studies included were randomized, placebo-controlled, double-blind trials of antidepressants for women diagnosed with breast cancer and depression. Studies were excluded if they were nonrandomized trials, had an active comparator, or if the antidepressant drug was not primarily used for depression. The severity of depressive symptoms was measured using standardized rating scales for depression. The risk of bias was assessed using the Cochrane risk of bias 2 tool. Covidence and Microsoft Excel were used for data extraction and RevMan 5.4.1 for efficacy outcome estimates, heterogeneity, and sensitivity analysis. Results: Of a total of 155 studies, 13 studies (9 parallel design and 4 crossover) met the inclusion criteria for systematic review and seven for meta-analysis involving 595 participants. The risk of bias assessment showed that five studies had low risk, four studies had some concerns, and four studies had high risk of bias. The antidepressants noted to have a favorable outcome were fluoxetine, paroxetine, mianserin, and mirtazapine. The pooled analysis (standardized mean difference [SMD] −0.28 [confidence interval = −0.56, 0.01] z = 1.87 [P = 0.06]) and subgroup analysis (selective serotonin reuptake inhibitor) did not favor antidepressants (SMD = −0.23 [−0.52, 0.07], z = 1.51, [P = 0.13]). Sensitivity analysis did not show a significant difference in outcome measures between antidepressants and placebo. Considerable heterogeneity, with a value of 69%, was found to be statistically significant (P = 0.003). Conclusion: We conclude that based on the available research, there was no evidence that antidepressants were superior to placebo in the management of depression in breast cancer. The possible reasons for heterogeneity are variations in the duration of study periods and antidepressant administration, different stages of breast cancer, and different scales used for assessing depression in RCTs.

We describe the design, synthesis and structure–activity relationship of a novel series of 1-(4-(7-azaindole)-3,6-dihydropyridin-1-yl)alkyl-3-(1H-indol-3-yl)pyrrolidine-2,5-dione derivatives with combined effects on the serotonin (5-HT1A) and dopamine (D2) receptors and the serotonin (5-HT), noradrenaline (NA), and dopamine (DA) transporters as multi-target directed ligands for the treatment of depression. All of the tested compounds demonstrated good affinity for the serotonin transporter (SERT). Among them, compounds 11 and 4 emerged as the lead candidates because of their promising pharmacological profile based on in vitro studies. Compound 11 displayed a high affinity for the 5-HT1A (Ki = 128.0 nM) and D2 (Ki = 51.0 nM) receptors, and the SERT (Ki = 9.2 nM) and DAT (Ki = 288.0 nM) transporters, whereas compound 4 exhibited the most desirable binding profile to SERT/NET/DAT among the series: Ki = 47.0 nM/167.0 nM/43% inhibition at 1 µM. These results suggest that compounds 4 and 11 represent templates for the future development of multi-target antidepressant drugs. [ABSTRACT FROM AUTHOR]

Background: Clinical practice guidelines recommend early serum electrolyte monitoring when starting antidepressants in older adults due to the increased risk of hyponatremia. It is unclear whether this monitoring improves outcomes. Methods: Population‐based, retrospective cohort study of Ontario adults aged ≥66 years who initiated therapy with a selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) between April 1, 2013, and January 31, 2020. The index date was the date of the first such prescription, and the exposure of interest was serum electrolyte measurement during the subsequent 7 days. The primary outcome was any emergency department or hospital admission with hyponatremia within 8–60 days of antidepressant initiation. Poisson regression models compared individuals who had versus did not have their serum electrolytes tested in the week following SSRI/SNRI initiation, weighting by propensity score‐based overlap weights. Results: Among the 420,085 patients aged ≥66 years initiating treatment with an SSRI/SNRI, 26,808 (6.4%) had serum electrolytes measured in the subsequent 7 days and 6109 (1.5%) subsequently presented to hospital with hyponatremia. The time from drug initiation to hospitalization varied (median 29, interquartile range [IQR] 17–44 days), and the median sodium concentration measured in the community (136, IQR 133–138 mmol/L) was marginally higher than those at the time of hospitalization (132, IQR 130–134 mmol/L). Patients who underwent electrolyte testing in the week following SSRI/SNRI treatment were more likely to attend an emergency department (ED) or hospital with hyponatremia within 8–60 days relative to those who did not (relative risk = 2.31, 95% confidence interval: 2.16–2.46). Conclusions: Testing serum electrolytes in the week after starting an SSRI/SNRI is not associated with a reduced risk of a hospital visit with hyponatremia. These findings do not support current guidelines recommending routine electrolyte monitoring. [ABSTRACT FROM AUTHOR]

Background: Smoking and the use of non-steroidal anti-inflammatory drugs (NSAIDs) acetylsalicylic acid (ASA), proton pump inhibitors (PPIs), serotonin reuptake inhibitors (SSRIs), and statins have been associated with microscopic colitis (MC). Objectives: We investigated whether these factors were associated with repeated budesonide treatments in patients diagnosed with MC. Design: Retrospective observational study. Methods: All patients with a histologically verified diagnosis of MC at our clinic between the years 2006 and 2022 were identified. Baseline factors and drugs prescribed before and after diagnosis were registered. The influence of risk factors on the odds of having a prescription of oral budesonide and the odds of having a second course of budesonide was studied. Results: Patients with MC (n = 183) with a mean age of 62.3 years [standard deviation (SD): 13.3 years] were followed for a median of 5 years (25th–75th percentile 4–10 years) after diagnosis. In all, 138 patients (75%) had at least one prescription of budesonide after diagnosis, and 90 patients (49%) had at least one clinical relapse treated with budesonide. Patients who had been prescribed NSAIDs within 1 year before clinical relapse had higher odds for clinical relapse [odds ratio (OR): 3.70, 95% confidence interval (CI): 1.06–12.9] but there was no increased risk for clinical relapse for the use of ASA (OR: 0.99, 95% CI: 0.39–2.90), PPIs (OR: 1.09, 95% CI: 0.45–2.63), SSRI (OR: 1.41, 95% CI: 0.82–2.44), or statins (OR: 0.83, 95% CI: 0.35–1.99). No association was seen between being a smoker and/or being prescribed NSAID, ASA, PPI, SSRI, and statins at baseline and the odds of having a prescription of oral budesonide within 1 year after diagnosis. Conclusion: The risk of being prescribed a second course of budesonide is associated with receiving a prescription of NSAIDs but not with the use of ASA, PPIs, SSRIs, and statins. Plain language summary: The use of drugs and the odds for patients with microscopic colitis of having a second course of budesonide Microscopic colitis is a common cause of chronic diarrhea. Previous studies have shown that the use of non-steroidal anti-inflammatory drugs, acetylsalicylic acid, proton-pump inhibitors, serotonin reuptake inhibitors and statins are used more often in patients who later develop microscopic colitis. We aimed to study if these drugs also had an association to an increased risk of disease flares treated with budesonide in 183 patients with known microscopic colitis. Oral budesonide for 6-8 weeks are recommended for disease flares of microscopic colitis. In our study, 90 patients (49%) were prescribed a second course of budesonide probably due to a disease flare. We found a higher odds for being prescribed a second course of budesonide in patients with microscopic colitis who were prescribed non-steroidal anti-inflammatory drugs but no higher risk for the other 'risk drugs' for microscopic colitis. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) ranks first in cancer incidence among women. For successful treatment of BC, depending on the molecular type and stage of the disease, chemotherapy is used, the side effects of which are manifested by menopausal symptoms, sexual dysfunction, and depressive states. However, not all patients after BC receive appropriate therapy for menopausal symptoms, what significantly worsens their quality of life. One of the symptoms that brings the most severe discomfort is the vasomotor symptom, a form of temperature dysfunction with peripheral vasodilation and increased cutaneous blood flow that results in increased heat loss. There are several types of drugs that are used to prevent menopausal symptoms in patients taking endocrine chemotherapy, many of which are in the experimental phase of development. In this review, we will try to identify proven effective and safe methods for correcting menopausal symptoms in women who underwent chemotherapy and endocrine therapy for BC.

Infections caused by Cryptococcus gattii mainly affect immunocompetent individuals and the treatment presents important limitations. This study aimed to validate the efficacy of selective serotonin reuptake inhibitors (SSRI), fluoxetine hydrochloride (FLH), and paroxetine hydrochloride (PAH) in vitro against C. gattii. The antifungal activity of SSRI using the microdilution method revealed a minimal inhibitory concentration (MIC) of 31.25 µg/ml. The combination of FLH or PAH with amphotericin B (AmB) was analyzed using the checkerboard assay and the synergistic effect of SSRI in combination with AmB was able to reduce the SSRI or AmB MIC values 4–8-fold. When examining the effect of SSRI on the induced capsules, we observed that FLH and PAH significantly decreased the size of C. gattii capsules. In addition, the effects of FLH and PAH were evaluated in biofilm biomass and viability. The SSRI were able to reduce biofilm biomass and biofilm viability. In conclusion, our results indicate the use of FLH and PAH exhibited in vitro anticryptococcal activity, representing a possible future alternative for the cryptococcosis treatment. [ABSTRACT FROM AUTHOR]

Prenatal exposure to maternal depression and serotonin reuptake inhibitor (SRI) antidepressants both affect the development of the hypothalamic–pituitary–adrenal (HPA) system, possibly via the neurotransmitter serotonin (5HT). In a community cohort, we investigated the impact of two factors that shape prenatal 5HT signaling (prenatal SRI [pSRI] exposure and child SLC6A4 genotype) on HPA activity at age 6 years. Generalized estimating equation (GEE) models were used to study associations between cortisol reactivity, pSRI exposure, and child SLC6A4 genotype, controlling for maternal depression, child age, and sex (48 pSRI exposed, 74 nonexposed). Salivary cortisol levels were obtained at five time points during a laboratory stress challenge: arrival at the laboratory, following two sequential developmental assessments, and then 20 and 40 min following the onset of a stress‐inducing cognitive/social task. Cortisol decreased from arrival across both developmental assessments, and then increased across both time points following the stress challenge in both groups. pSRI‐exposed children had lower cortisol levels across all time points. In a separate GEE model, we observed a lower cortisol stress response among children with LG/S alleles compared with children with La/La alleles, and this was particularly evident among children of mothers reporting greater third trimester depressed mood. Our findings suggest that pSRI exposure and a genetic factor associated with modulating 5HT signaling shaped HPA reactivity to a laboratory stress challenge at school age. [ABSTRACT FROM AUTHOR]

Serotoninergic signaling is identified as a crucial player in psychiatric disorders (notably depression), presenting it as a significant therapeutic target for treating such conditions. Inhibitors of serotoninergic signaling (especially selective serotonin reuptake inhibitors (SSRI) or serotonin and norepinephrine reuptake inhibitors (SNRI)) are prominently selected as first-line therapy for the treatment of depression, which benefits via increasing low serotonin levels and norepinephrine by blocking serotonin/norepinephrine reuptake and thereby increasing activity. While developing newer heterocyclic scaffolds to target/modulate the serotonergic systems, imidazole-bearing pharmacophores have emerged. The imidazole-derived pharmacophore already demonstrated unique structural characteristics and an electron-rich environment, ultimately resulting in a diverse range of bioactivities. Therefore, the current manuscript discloses such a specific modification and structural activity relationship (SAR) of attempted derivatization in terms of the serotonergic efficacy of the resultant inhibitor. We also featured a landscape of imidazole-based development, focusing on SAR studies against the serotoninergic system to target depression. This study covers the recent advancements in synthetic methodologies for imidazole derivatives and the development of new molecules having antidepressant activity via modulating serotonergic systems, along with their SAR studies. The focus of the study is to provide structural insights into imidazole-based derivatives as serotonergic system modulators for the treatment of depression. [ABSTRACT FROM AUTHOR]

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Purpose of Review: When persistent postural-perceptual dizziness (PPPD) entered the diagnostic nomenclature in 2017, treatment options were adopted from its predecessors, including use of vestibular rehabilitation, psychotherapy, and serotonin reuptake inhibitors. Individualised treatment may require additional interventions to cover the full range of precipitating and perpetuating factors and medical and psychiatric comorbidities associated with PPPD. This article aims to review available and emerging treatment strategies for this prevalent functional neurological disorder and provides practical recommendations for personalising therapy. Recent Findings: As our knowledge of the underlying causes of PPPD continues to grow, evidence for the best treatment approach is still limited but accumulating. Vestibular rehabilitation, cognitive-behavioural therapy (CBT), and serotonin reuptake inhibitors, alone or in combination, can be beneficial with similar treatment effects in reducing dizziness handicap scores. Newer treatments that have been explored include self-help programmes of vestibular exercises, virtual reality, and electrical stimulation therapies. Summary: For individuals with PPPD, vestibular rehabilitation, CBT, and medication, and ideally for many patients a combination of more than one of these, can assist in breaking a cycle of maladaptive balance control that reinforces patient symptoms. Further evidence from larger randomised controlled studies with longer follow-up periods is needed. [ABSTRACT FROM AUTHOR]

ObjectiveIctal (ICA) and postconvulsive central apnea (PCCA) have been implicated in sudden unexpected death in epilepsy (SUDEP) pathomechanisms. Previous studies suggest that serotonin reuptake inhibitors (SRIs) and benzodiazepines (BZDs) may influence breathing. The aim of this study was to investigate if chronic use of these drugs alters central apnea occurrence in patients with epilepsy.MethodsPatients with epilepsy admitted to epilepsy monitoring units (EMUs) in nine centers participating in a SUDEP study were consented. Polygraphic physiological parameters were analyzed, including video-electroencephalography (VEEG), thoracoabdominal excursions, and pulse oximetry. Outpatient medication details were collected. Patients and seizures were divided into SRI, BZD, and control (no SRI or BZD) groups. Ictal central apnea and PCCA, hypoxemia, and electroclinical features were assessed for each group.ResultsFour hundred and seventy-six seizures were analyzed (204 patients). The relative risk (RR) for ICA in the SRI group was half that of the control group (p = 0.02). In the BZD group, ICA duration was significantly shorter than in the control group (p = 0.02), as was postictal generalized EEG suppression (PGES) duration (p = 0.021). Both SRI and BZD groups were associated with smaller seizure-associated oxygen desaturation (p = 0.009; p ≪ 0.001). Neither presence nor duration of PCCA was significantly associated with SRI or BZD (p ≫ 0.05).ConclusionsSeizures in patients taking SRIs have lower occurrence of ICA, and patients on chronic treatment with BZDs have shorter ICA and PGES durations. Preventing or shortening ICA duration by using SRIs and/or BZD in patients with epilepsy may play a possible role in SUDEP risk reduction.

Obsessive-compulsive disorder (OCD) affects 1–2% of children and is associated with functional impairment and diminished quality of life. Several treatments are efficacious: cognitive behavioral therapy (CBT) with exposure and response prevention, serotonin reuptake inhibitor (SRI) monotherapy, and combined treatment (SRI ​+ ​CBT). Expert clinician-informed practice parameters suggest that youth with mild to moderate OCD should be treated initially with CBT yet SRIs are frequently employed as the first-line intervention or in combination with psychotherapy in applied practice. Empirical data to guide SRI discontinuation in pediatric OCD are very limited. This study, Promoting OCD Wellness and Resiliency (POWER), aims to address this gap through a two phase, double-blinded, placebo-controlled, randomized controlled non-inferiority trial with the purpose of evaluating whether youth with OCD on an SRI can discontinue their medication after successful CBT augmentation and maintain wellness for a period of 24 weeks during which they receive maintenance CBT that models standard-of-care. In this paper we describe the rationale and methodological design of the POWER study.

Abstract Background Bleedings are frequent and dreaded complications in heart failure patients with ventricular assist devices (VAD). Serotonin reuptake inhibitor (SRI) antidepressants are widely used to treat depression in these patients, though they are attributed an increased risk of bleeding due to their modification of hemostasis. Evidence on bleeding risk of VAD patients under SRI medication is scarce and limited. We therefore aimed to assess if SRI use is associated with an elevated bleeding risk in this particularly vulnerable population. Methods We analyzed the medical records of 92 VAD patients at the University Heart Center Zurich between September 2004 and April 2018 for the occurrence of bleedings and the concomitant use of an SRI. Bleeding was defined as any type of post-implantation bleeding requiring medical treatment. We performed univariate analyses and linear mixed-effects models, adjusting for baseline clinical characteristics as potential predictors to identify differences in bleeding rates in patients with vs. without SRI intake. Results The cohort comprised 60.9% of patients with a continuous-flow VAD and 39.1% with a pulsatile-flow VAD. A total of 77.2% of patients experienced at least one bleeding incident. Overall, 28.6% of bleedings occurred under SRI therapy. A generalized linear mixed model showed a predictive effect of SRI medication on bleeding rate, independent of VAD type (z = 2.091, p = 0.037). Conclusions Bleeding events in heart failure patients occur frequently after VAD implantation. Patients with SRI medication were at increased risk of bleeding. The indication and use of SRI, therefore, should be considered carefully.

Background: Post-stroke depression (PSD) is the most frequent mental illness after stroke, affecting about 30% of stroke survivors and hampering rehabilitation outcome. While current guidelines recommend monitored antidepressant treatment (ADT) in PSD, the limited precision between the use and need of ADT in clinical practice remains underassessed and poorly understood. Methods: Depression according to DSM criteria and ADT was assessed in n = 294 stroke survivors from two German rehabilitation centers about one, six, and twelve months after stroke. At each measurement occasion, PSD and current use of ADT was assessed, leading to four subgroups: PSD (yes/no) and ADT (yes/no). Frequencies of ADT and PSD were examined and analyzed with regard to depression severity (minor/major). Intra-individual trajectories were used to assess the persistence in ADT over- and undertreatment from a longitudinal perspective. Results: After one, 6 and 12 months, 36.7%, 31.1% and 25.5% of stroke survivors fulfilled the criteria for depression. Across all measurement occasions, 53% of depressed stroke survivors did not receive ADT, while 12% of the non-depressed did. ADT between stroke survivors with major or minor depression differed at baseline but not thereafter. Between 15-40% of the depressed without ADT experienced persisting undertreatment and 25-50% the non-depressed with ADT had not fulfilled depression criteria at an earlier time point. Conclusions: Depression occurred in one in three stroke survivors. Among these, only one in two received ADT, irrespective of PSD severity after discharge. In contrast, one in eight stroke survivors without depressive disorder received ADT, about half of them in the absence of earlier PSD. In conclusion, we found evidence of both under- and overtreatment of PSD with ADT, which emphasizes the need for a more stringent implementation of current PSD guideline recommendations. [ABSTRACT FROM AUTHOR]

Background: Personality is one of the most important factors affecting the treatment course of patients with psychiatric disorders. Objective: The present study aimed to find the possible relationship between personality factors and response to selective serotonin reuptake inhibitors treatment for major depression. Method: One hundred and seven patients with mild or moderate major depression treated with citalopram, sertraline or fluoxetine for two months enrolled in the present prospective study. Every patients were evaluated by Hamilton depression test (as pre-test and post-test) and Temperament and Character Inventory questionnaire (as pre-test) and their response to treatment evaluated base on their Hamilton depression test. Results: The mean age of the patients was 39.7 years and most of the population were female (71.9%). The results showed that reward dependence (OR=1.18, P =0.05), age (OR=1.07, P=0.002) and cooperativeness (OR=0.76, P <0.001) had significant effect on the likelihood of being non-responsiveness to the treatment. Logistic regression showed that the effect of temperament and character, gender, age, and depression score at the beginning of the treatment indicated that only cooperativeness (B =-0.21, P<0.01) predicted response to treatment. Conclusion: Temperament and character or at least some of their traits may predispose response to depression treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Serotonin toxicity is a known side effect of selective serotonin reuptake inhibitors and has previously also been described as a possible side effect of 5-hydroxytryptamine receptor agonist (triptan) medications. However, the literature is conflicted about the risk of developing serotonin toxicity as a result of drug interaction between selective serotonin reuptake inhibitors and triptans. Case presentation A 30-year-old Caucasian woman with a history of depression on regular fluvoxamine presented to the emergency department with right-sided facial and lower limb twitching. The patient had recently been prescribed sumatriptan for migraines and had taken her first ever dose shortly prior to the onset of symptoms. She was tachycardic, diaphoretic, and hypertonic on initial assessment with bilateral lower limb and ocular clonus. Electrocardiogram showed sinus tachycardia with QT interval under the treatment interval, and pathology and imaging findings were unremarkable. Her symptoms improved with supportive management and cyproheptadine. Conclusions This patient’s presentation fulfilled both Sternbach and Hunter criteria for serotonin toxicity, illustrating a potential case of serotonin toxicity as a result of drug interaction between a selective serotonin reuptake inhibitor and a triptan.

Eating disorders, like binge eating, have a strong association with schizophrenia. Illness characteristics like disordered eating, cognition, and behavior can lead to eating disorders. Previous research highlighted the neurobiological structural similarity and the role of hormonal factors, like hypocretin, in the etiology of eating disorders in schizophrenia. Modifying the obesogenic environment by adapting healthy eating styles has been effective in reducing binging episodes. Antipsychotic medications also have a role in altering eating patterns that result in binge eating disorder. Adolescents with psychosis have a higher incidence of eating disorders. Here, we present an elderly female with schizophrenia who had obesogenic behaviors along with binge eating disorder. Interestingly, the patient had atypical age of onset and presentation and no psychopathological symptoms as a reason for binging.

Background: Brain ventricles have been reported to be enlarged in several neuropsychiatric disorders and in aging. Whether human cerebral ventricular volume can decrease over time with psychiatric treatment is not well-studied. The aim of this study was to examine whether inpatients taking serotonin reuptake inhibitors (SRI) exhibited reductions in cerebral ventricular volume. Methods: Psychiatric inpatients, diagnosed mainly with depression, substance use, anxiety, and personality disorders, underwent two imaging sessions (Time 1 and Time 2, approximately 4 weeks apart). FreeSurfer was used to quantify volumetric features of the brain, and ANOVA was used to analyze ventricular volume differences between Time 1 and Time 2. Inpatients' brain ventricle volumes were normalized by dividing by estimated total intracranial volume (eTIV). Clinical features such as depression and anxiety levels were collected at Time 1, Time 1.5 (approximately 2 weeks apart), and Time 2. Results: Inpatients consistently taking SRIs (SRI +, n = 44) showed statistically significant reductions of brain ventricular volumes particularly for their left and right lateral ventricular volumes. Reductions in their third ventricular volume were close to significance (p =.068). The inpatients that did not take SRIs (SRI-, n = 25) showed no statistically significant changes in brain ventricular volumes. The SRI + group also exhibited similar brain structural features to the healthy control group based on the 90% confidence interval comparsions on brain ventricular volume parameters, whereas the SRI- group still exhibited relatively enlarged brain ventricular volumes after treatment. Conclusions: SRI treatment was associated with decreased brain ventricle volume over treatment. [ABSTRACT FROM AUTHOR]

Background: Obsessive-compulsive disorder (OCD) symptom dimensions respond differently to behavioral and pharmacological interventions, and some dimensions are reported to be more resistant to treatment. Aim: We aimed to investigate the responses of three symptom dimensions (harm/sexual, symmetry/hoarding, and contamination/cleaning) to serotonin reuptake inhibitor (SRI) therapy in pediatric OCD. Methods: Children who were between 6 and 17 years old, diagnosed with OCD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, followed up at our clinic for at least 3 months, and received SRI treatment were included in our study. Response to treatment was assessed using the Clinical Global Impressions scale. Predictors of treatment response were analyzed using regression models. Results: Of the 102 children with a mean age of 11.84 ± 2.87 years, 57.8% were male and the mean follow-up period was 12.39 ± 9.55 months. The overall response rate to pharmacotherapy was 66.7%. Patients with symmetry/hoarding symptoms [relative risk (RR) = 0.66, 95% confidence interval (CI) (0.12–0.79), P = 0.015] did not respond as well to SRIs. Besides, adolescent age (RR = 0.65, 95% CI (0.10–0.73), P = 0.01) was associated with a less favorable SRI response. Conclusion: This study shows that symptom dimensions are one of the factors predicting response to pharmacotherapy in pediatric OCD. It is hypothesized that considering the dimensions is important to plan more appropriate treatment and provide more accurate prognostic information when assessing children with OCD. [ABSTRACT FROM AUTHOR]

Introduction Obsessive-Compulsive Disorder (OCD) is a common mental disorder and a major cause of disability worldwide. Typically, it has a chronic course, marked by recurrent intrusive thoughts (obsessions) and repetitive behaviors (compulsions). Its pharmacological first line of treatment has been well established for several years now, with the Serotonin Reuptake Inhibitors (SRIs). However, about half of the patients are resistant to this approach, representing a therapeutic challenge for clinicians. Evidence suggests that other medications can augment SRIs, enhancing its effects and achieving a bigger efficacy in these patients’ treatment. Also, there is an increasing interest in neurosurgical interventions in these patients. Objectives The main goal of this work was to assess the clinical efficacy of adjunctive therapeutic strategies in patients with OCD resistant to SRIs. Methods A literature review was conducted searching PubMed and ScienceDirect databases from the 1st of January 2000 to the 1st of September 2021 to identify clinical trials comparing an active drug/neurosurgical intervention with placebo as an adjunctive therapeutic strategy in SRI-resistant OCD. Results Sixteen studies were selected for data extraction, including a total of 585 patients. Risperidone, aripiprazole, N-acetylcysteine, lamotrigine, pindolol, riluzole, memantine and methylphenidate were efficacious for augmenting SRIs in OCD. Ablative surgery (ABL) and deep brain stimulation (DBS) were equal effective in the treatment of refractory OCD. Conclusions Several therapeutic options presented as potentially effective in OCD when it is resistant to SRIs, although this is still an area for further research. Disclosure No significant relationships.

Background: Bleedings are frequent and dreaded complications in heart failure patients with ventricular assist devices (VAD). Serotonin reuptake inhibitor (SRI) antidepressants are widely used to treat depression in these patients, though they are attributed an increased risk of bleeding due to their modification of hemostasis. Evidence on bleeding risk of VAD patients under SRI medication is scarce and limited. We therefore aimed to assess if SRI use is associated with an elevated bleeding risk in this particularly vulnerable population.Methods: We analyzed the medical records of 92 VAD patients at the University Heart Center Zurich between September 2004 and April 2018 for the occurrence of bleedings and the concomitant use of an SRI. Bleeding was defined as any type of post-implantation bleeding requiring medical treatment. We performed univariate analyses and linear mixed-effects models, adjusting for baseline clinical characteristics as potential predictors to identify differences in bleeding rates in patients with vs. without SRI intake.Results: The cohort comprised 60.9% of patients with a continuous-flow VAD and 39.1% with a pulsatile-flow VAD. A total of 77.2% of patients experienced at least one bleeding incident. Overall, 28.6% of bleedings occurred under SRI therapy. A generalized linear mixed model showed a predictive effect of SRI medication on bleeding rate, independent of VAD type (z = 2.091, p = 0.037).Conclusions: Bleeding events in heart failure patients occur frequently after VAD implantation. Patients with SRI medication were at increased risk of bleeding. The indication and use of SRI, therefore, should be considered carefully. [ABSTRACT FROM AUTHOR]

Objective: Sexual dysfunctions (SD) are very common in patients with psychiatric disorders and may be due to the side effects of the disease or medications used. Current scales cannot distinguish whether SDs are due to psychiatric illness or medications use. The Psychotropic Associated Sexual Dysfunction Questionnaire (PRSexDQ) is a customized scale for screening SD due to drug use. Our aim is to conduct a validity and reliability study of PRSexDQ in patients using selective serotonin reuptake inhibitors (SSRIs)., Method: One hundred patients who applied to psychiatry outpatient clinic and received SSRI treatment for at least 1 month were included in the study. These patients were evaluated by a psychiatrist, and completed the PRSexDQ-T, Arizona Sexual Experience Scale (ASEX), Golombok Rust Inventory Sexual Satisfaction (GRISS)., Result: The Cronbach's Alpha coefficient was calculated as 0.906 for the analysis performed to evaluate the internal consistency of the PRSexDQ-T. In the item-total score analysis, the correlation of all items with the total score was found to be quite high (above 0.7). Correlation coefficients were found between 0.939 and 0.985, which was used to determine the test-retest correlation for each item, and all values were statistically significant (p<0.01). In the Pearson correlation analysis performed for validity analysis, a large positive correlation was found between PRSexDQ-T and ASEX and GRISS male-female total and subscale scores., Conclusion: The Turkish version of PRSexDQ is a valid and reliable measurement tool in the sample of patients using SSRIs to evaluate the level of sexual dysfunction.

This study examined the cost-effectiveness of deep transcranial magnetic stimulation (dTMS) for treatment refractory obsessive-compulsive disorder (OCD) relative to other established treatment options, including antidepressant medication (ADM), ADM + antipsychotic augmentation, real-world cognitive-behavioral therapy (ADM + CBT Effectiveness), clinical trial CBT (ADM + CBT), intensive outpatient program (IOP), partial hospitalization program (PHP), and PHP to IOP stepdown. A decision analytic model was developed to evaluate the cost-effectiveness of dTMS relative to other established treatment alternatives for adults (18–64 years old) with refractory OCD. Building on Gregory et al. (2018), the model was parameterized with probabilistic and deterministic parameters from the literature and an outcomes database to perform a Monte Carlo simulation of a hypothetical cohort of 100,000 adults with OCD to estimate costs, and incremental cost-effectiveness ratio (ICER) for dTMS relative to each treatment strategy. Encounters took place from 2012 to 2015. Data for dTMS were taken from a recent multisite study. Although dTMS fit between ADM and ADM + CBT in overall costs, ADM + CBT had the lowest ICER and thus would be chosen before dTMS. dTMS was determined to be more cost effective relative to PHP/IOP stepdown, PHP, and IOP. dTMS is cost-effective, along the treatment continuum from outpatient medication management and CBT to more intensive, facilities-based approaches, and may be an incremental strategy to employ when higher intensity strategies are either not available, not financially feasible, or whilst on extended waits for admission to these higher levels of care. [ABSTRACT FROM AUTHOR]

Objective: Meta‐analyses have established a heightened risk of suicidality for youth treated with selective serotonin reuptake inhibitors (SSRIs). The present study investigates the risk and possible predictors of suicidality and non‐suicidal self‐injury (NSSI) associated with SSRI treatment in a clinical sample of children and adolescents. Methods: An observational, longitudinal, retrospective study using a within‐subject study design including in‐ and outpatients aged 0–17 years treated with SSRIs. Data were obtained from digital medical records and prescription software. Results: N = 365 patients were included (64.1% female), mean (SD) age 14.5 (2.04) years, with primary depression, anxiety or obsessive‐compulsive disorder. No suicides occurred. When comparing the 6‐week period immediately prior to versus following SSRI initiation, the patient proportion with broadly defined suicidality decreased (38.5% vs. 24.2%, p < 0.001) while the proportion with suicide attempts was stable (2.8% vs. 2.8%, p = 1.000). The proportion with NSSI decreased statistically non‐significantly (12.4% vs. 8.4%, p = 0.067). Results from individually standardized observation periods were similar; however, the proportion with suicide attempts decreased statistically non‐significantly and the proportion with NSSI decreased significantly. Suicidality during SSRI treatment was associated with previous suicidality (OR[CI] = 6.0 [2.4–14.8], p < 0.001), depression as indication for SSRI treatment (OR[CI] = 2.1 [1.2–3.7], p = 0.01), female sex (OR[CI] = 2.1 [1.1–4.1], p = 0.02) and previous NSSI (OR[CI] = 2.0 [1.2–3.5], p = 0.01). Conclusion: Suicidality was common in youth treated with SSRIs. The patient proportion with overall suicidality decreased, and the proportion with attempted suicide was stable in the weeks following SSRI initiation. Previous suicidality, depression, female sex and previous NSSI are important predictors for suicidality during SSRI treatment in youth. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder (MDD) and anxiety disorders are both common and especially challenging during pregnancy. Considering possible risks of intrauterine drug exposure of the child, the role of psychopharmacological treatment is ambiguous and various negative obstetric outcomes were inconsistently associated with medication. Consequently, a critical examination of peri‐ and postnatal phenomena associated with intrauterine exposure to antidepressants based on serotonin reuptake inhibition (SRI) and subsumed under the term "poor neonatal adaptation syndrome" (PNAS) is urgently called for. Methods: A comprehensive literature search was conducted, revealing a total number of 33 relevant studies and 69 individual outcomes among 3025 screened studies. Seventeen outcomes allowed meta‐analytic evaluation (random effects model). Measures for heterogeneity (I2) and contour‐enhanced funnel plots were generated. Results: Single studies showed increased risks for deficits in neurological functioning and autonomous adaptation in SRI exposed infants. Meta‐analytical evaluation showed increased symptom occurrence or severity in exposed neonates for low APGAR scores, birth weight, size for gestational age, preterm delivery, neuromuscular and autonomous regulation, and higher rates of admission to specialized care. Mostly, increased risk after SRI exposure was supported by comparison to unexposed infants born to mothers diagnosed with depression. Conclusion: Whereas statistically significant evidence for various effects of intrauterine exposure to SRI was found, the clinical relevance remains unresolved because of inherently low data quality in this research domain and insufficiently defined samples and outcomes. More systematic research under ethical considerations is required to improve multiprofessional counseling in the many women dealing with MDD during pregnancy and the peripartum. [ABSTRACT FROM AUTHOR]

About half of the patients with Obsessive-compulsive disorder (OCD) do not respond to serotonin reuptake inhibitors (SRIs) or have a partial improvement in their symptoms. This study aimed to compare the efficiency and safety of aripiprazole, olanzapine, and L-methyl folate in patients with resistant OCD. The study consisted of an open-label prospective phase of 12-weeks to ascertain resistance to SRIs and a second 6-week open-label addition phase for non or, partial responders of the first phase. One-hundred-fifteen patients entered the 16-week open-label phase. Fifty patients (43.47%) responded to the SRIs monotherapy, two patients developed adverse effects and another three were lost to the follow up. Sixty patients (52.2%) were considered treatment-resistant and entered the 6-week open-label aripiprazole, olanzapine, or L-methyl folate addition phase; Patients showed a significant improvement over 6-week study period in olanzapine and aripiprazole group as measured by YBOCS total score (p < 0.001) while there was no change in the L-methyl folate group at the end as compared with baseline (p = 0.150). Clinical Global Impression-Severity decreased from 4.90 to 2.90 in olanzapine and aripiprazole group at the end of 6 weeks while there was no change in the L-methyl folate group. The CGI-I was significant in the olanzapine and aripiprazole group (p < 0.001) while it was insignificant in the L-methyl folate group (p = 0.088). Augmentation of SRIs with olanzapine or aripiprazole could be a promising option for resistant OCD. L-methyl folate though shown to be effective in resistant depression was not effective in treatment resistant OCD. [ABSTRACT FROM AUTHOR]