Sertraline induced acute hepatocellular liver injury in patient with major depressive disorder: a case report.

This case report describes a patient with major depressive disorder (MDD) who developed acute hepatocellular liver injury after being treated with sertraline, a selective serotonin reuptake inhibitor (SSRI). The diagnosis of MDD was made two years prior, and the patient had previously responded partially to escitalopram and cognitive-behavioral therapy (CBT). Upon switching to sertraline 50 mg daily, the patient presented with severe symptoms indicative of acute liver injury, including elevated liver enzymes, jaundice, and gastrointestinal distress. Following the discontinuation of sertraline, the patient's liver function tests gradually normalized over a 90-day period, confirming the diagnosis of sertraline-induced hepatotoxicity. This case underscores the importance of continuous monitoring for potential liver injury in patients treated with sertraline. The findings contribute to the existing body of evidence on the hepatotoxic risks associated with SSRIs and highlight the need for personalized treatment strategies to mitigate adverse effects and enhance patient safety. Further research is needed to explore the long-term safety and efficacy of sertraline, particularly in vulnerable populations.

Yawning as a Rare Side Effect With Increased Escitalopram Dose: A Case Report.

Yawning is a normal physiological process that occurs naturally in all human beings in different settings, such as hunger, drowsiness, or stress. It is typically harmless, but abnormal yawning can be seen in many medical conditions. In psychiatry, it frequently occurs in disorders like depression, insomnia, and anxiety due to disturbed sleep. It has also been observed as an adverse reaction of some drugs, like escitalopram, a selective serotonin reuptake inhibitor. Escitalopram is a widely prescribed, well-tolerated antidepressant and antianxiety drug that can induce a range of side effects, one of which is excessive yawning. Its excessive occurrence can be distressing for patients, affecting their socio-occupational functioning. Clinically, differentiating yawning induced by escitalopram treatment from that in depression can be a diagnostic hurdle. Awareness and recognition of this lesser known side effect can improve patient outcomes by allowing for timely adjustments and easing the discomfort.

A Randomized Controlled Trial Comparing the Quality of Life and Medication Adherence in Patients on Antidepressant Monotherapy.

Background and objectives The quality of life declines with the growing severity of major depressive disorder (MDD). In depressed people, medication adherence and the quality of life are mutually corrosive. These concerns spurred the investigation of relationships between treatment outcomes and adherence levels. Limited studies are looking at how vortioxetine, escitalopram, and vilazodone affect these parameters. We aimed to detect how the Short Form-36 (SF-36) had changed 16 weeks after the baseline. The connection between treatment results (as expressed by the Hamilton Depression Rating Scale or HDRS) and medication adherence (as reflected by the Morisky Medication Adherence Scale-8 or MMAS-8) was also explored. Methods An open-label, randomized, three-arm trial with 96 MDD patients was conducted. For 16 weeks, the participants were put into three groups per a 1:1:1 ratio and administered tablets of vilazodone (20-40 mg/day), escitalopram (10-20 mg/day), or vortioxetine (5-20 mg/day). There were two test drugs: vilazodone and vortioxetine; the control was escitalopram. Four weeks apart, follow-up appointments were set after the baseline visit. The HDRS, mental and physical components of SF-36, and MMAS-8 scores were evaluated in the per-protocol (PP) population. Reduced HDRS scores were indicative of improved depression symptoms. Higher MMAS-8 and SF-36 scores indicated high drug adherence and enhanced quality of life. Our analysis used the Kruskal-Wallis test, the Bonferroni correction, and the Sankey diagram. In the Clinical Trial Registry-India (CTRI), we recorded this study prospectively (2022/07/043808). Results One hundred nine (81.34%) of the 134 individuals we examined were eligible. The PP population consisted of 96 (88.07%) of them who wrapped up the 16-week study. The mean age of the group was 46.3 ± 6.2 years. For each of the three groups, the SF-36 physical component scores revealed a median difference of 24.5 (23.8-26.0), 24.0 (22.8-25.3), and 27.0 (25.0-29.0) (p = 0.001). Accordingly, the mental components of their SF-36 scores showed a median difference of 32.0 (31.0-33.3), 31.0 (29.8-34.3), and 36.0 (33.0-38.0) (p = 0.001). A median difference of -15.0 (-16.0 to -14.0), -16.0 (-17.0 to -15.0), and -16.0 (-17.0 to -15.8) was observed in the HDRS scores after 16 weeks, with respect to the baseline (p < 0.001). The median MMAS-8 scores at 16 weeks were 6.0 (6.0-7.0), 6.8 (6.0-7.0), and 7.5 (6.5-8.0) (p = 0.031). The Sankey diagram illustrated the connection between better treatment results, increased medication compliance, and decreased symptoms of depression. Conclusion In comparison to vilazodone and escitalopram, vortioxetine demonstrated a statistically significant decrease in HDRS scores and an improvement in the physical and mental component scores of the SF-36. Clinical improvements were evident in the individuals' drug adherence levels. Larger-scale studies are advised to investigate the effects of these medications on the quality of life, medication adherence, and treatment outcomes.

Cutaneous Small-Vessel Vasculitis Induced by Escitalopram: A Case-Based Brief Review of the Literature.

A 65-year-old male with multiple comorbidities and recently diagnosed with diabetic kidney disease developed upper and lower extremity rash following escitalopram initiation for his depressive mood. Clinical assessment and skin biopsy confirmed cutaneous small-vessel vasculitis (CSVV), prompting drug discontinuation and oral methylprednisolone therapy. The resolution of the rash was achieved within a week. This rare case of CSVV induced by escitalopram highlights the importance of timely recognition and management of drug-induced CSVV and adds to the limited literature on selective serotonin reuptake inhibitor-associated CSVV.

Serum brain-derived neurotrophic factor, Val66Met polymorphism and open-label SSRI treatment response in Major Depressive Disorder.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been implicated in the therapeutic action of antidepressants and possibly in the pathophysiology of Major Depressive Disorder (MDD). Clinical studies of peripheral blood levels of BDNF in MDD have provided conflicting results, and there are also conflicting reports regarding the predictive value of peripheral BDNF levels for antidepressant treatment response. The present study investigated the association between serum BDNF levels, the BDNF Val66Met polymorphism (rs6265), clinical characteristics and SSRI treatment response. METHODS: This open-label clinical trial included 99 physically healthy, unmedicated MDD participants and 70 healthy controls. Following a baseline assessment, 53 of the MDD participants completed an eight-week, open-label course of SSRI antidepressant treatment. Serum BDNF levels and Hamilton Rating Scale for Depression (HDRS) ratings were examined at baseline and after eight weeks of treatment. Antidepressant response was defined as a decrease in HDRS ratings of > 50% from baseline to the end-of-treatment. Finally, serum BDNF levels and SSRI treatment response were compared between MDD participants who were heterozygous or homozygous for the Met allele ("Met-carriers") and individuals homozygous for the Val allele. RESULTS: Serum BDNF levels at baseline were significantly higher in the unmedicated MDD participants compared to healthy controls (15.90 ng/ml vs 13.75 ng/ml, t (167) = -2.041, p = 0.043). In a post-hoc analysis, this difference was seen in the female but not male participants (16.85 ng/ml vs 14.06 ng/ml, t (91) = -2.067, p = 0.042; 14.86 ng/ml vs 13.31 ng/ml, t (74) = -0.923, p = 0.359). Baseline serum BDNF levels were not associated with treatment responder status or with absolute change in depression ratings over the course of 8-week SSRI treatment (p = 0.599). In both Responders and Non-responders, no significant changes in serum BDNF levels were found over the 8-week period of SSRI-treatment (16.32 ng/ml vs 16.23 ng/ml, t (18) = 0.060, p = 0.953; 16.04 ng/ml vs 15.61 ng/ml, t (29) = 0.438, p = 0.665, respectively). Further, no differences were found in serum BDNF levels prior to treatment between MDD Met-carriers and MDD Val/Val homozygotes (15.32 ng/ml vs 16.36 ng/ml, t (85) = 0.747, p = 0.457), and no differences were found in post-treatment serum BDNF (F1,42= 0.031, p = 0.862). However, MDD Val/Val homozygotes showed significantly greater antidepressant responses at week 8 than did MDD Met-carriers (F1,46 = 4.366, p = 0.043). CONCLUSION: Our results do not support sufficient reliability of using peripheral BDNF to characterize depression or to predict antidepressant response in clinical use. The role of sex in moderating BDNF differences in depression, and the role of BDNF gene polymorphisms in predicting antidepressant response, remain to be further investigated. We conclude that, while central nervous system BDNF is likely involved in antidepressant efficacy and in aspects of MDD pathophysiology, its reflection in serum BDNF levels is of limited diagnostic or prognostic utility.

Exploring Esketamine's Therapeutic Outcomes as an FDA-Designated Breakthrough for Treatment-Resistant Depression and Major Depressive Disorder With Suicidal Intent: A Narrative Review.

The expansive spectrum of major depressive disorder (MDD) continues to pose challenges for psychiatrists to treat effectively. Oral antidepressant (OAD) medications that alter monoamine neurotransmitters, mainly selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs), have been the mainstay of therapy for decades. Although these drugs have been largely beneficial, a considerable subset of patients do not respond adequately to multiple conventional therapies administered for an appropriate length of time, leading to a diagnosis of treatment-resistant depression (TRD). Ketamine, a non-monoaminergic drug, has long been known for its beneficial effects on TRD when given intravenously (IV). Between 2019 and 2020, an intranasal formulation of the S (+) enantiomer of racemic ketamine, esketamine (ESK), was granted "breakthrough designation" by the FDA and approved for the indications of TRD and MDD patients exhibiting acute suicidal intent. The objective of this narrative review was to review the academic literature and collect clinical evidence that may corroborate intranasal ESK's effectiveness for its approved indications while addressing its safety and tolerability profile, adverse effects, and impact on cognition. An overview of the drug's origins, pharmacology, and standard treatment regimen are provided. The outcomes from double-blinded randomized control trials (DB-RCTs) of ESK are outlined to demonstrate the efficacy and safety data leading to its FDA approval, along with its long-term post-market safety outcomes. Comparative trials between ESK and ketamine are then evaluated to highlight ESK's consideration as a more practical alternative to ketamine in common clinical practice. The authors further discuss currently approved and developing therapies for TRD, propose future research directions, and identify the inherent limitations of the review and further research. To conduct the research required, three digital databases (PubMed, Medline, and ClinicalTrials.gov) were queried to search for key terms, including ketamine, esketamine, treatment-resistant depression, and biomarkers, using automation tools along with selective search engine results. After streamlining the results by title and abstract and removing duplicates, a total of 37 results were chosen, of which 18 are clinical trials. A reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) score was the primary efficacy endpoint for most of these clinical trials. In conclusion, intranasal ESK, when used as an adjunct to market OADs, shows greater efficacy in treating TRD and MDD with suicidal intent compared to OADs and placebo alone and provides a more suitable alternative to IV ketamine. It is important to note that further research is required to fully understand the novel mechanism of action of ESK, as well as the establishment of a consensus definition of TRD, which may facilitate better detection and treatment protocols. More focused quantitative and qualitative ESK studies are needed, as well as those pertaining to its use in patients with co-existing mental illnesses.

Design, synthesis, and biological evaluation of aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7.

Serotonin reuptake inhibition combined with the action targeting 5-hydroxytryptamine receptor subtypes can serve as a potential target for the development of antidepressant drugs. Herein a series of new aralkyl piperazines and piperidines were designed and synthesized by the structural modifications of the previously discovered aralkyl piperidine compound 1, targeting SSRI/5-HT1A/5-HT7. The results exhibited that compound 5a showed strong binding to 5-HT1A and 5-HT7 (Ki of 0.46 nM, 2.7 nM, respectively) and a high level of serotonin reuptake inhibition (IC50 of 1.9 nM), all of which were significantly elevated compared to 1. In particular, compound 5a showed weaker inhibitory activity against hERG than 1, and demonstrated good stability in liver microsomes in vitro. The preliminary screening using FST indicated that orally administered 5a, at a high dose, could reduce immobility time in mice markedly, indicating potential antidepressant activity.

Effect of Vortioxetine in Comparison to Fluoxetine on Metabolic Parameters in Patients With Depressive Disorder: A Randomized Controlled Trial.

Background Major depressive disorder (MDD) is a debilitating mood disorder that increases the risk of metabolic syndrome (MS), emphasizing the need for mental and physical health treatments. Although many studies have linked atypical antipsychotics to metabolic disturbances, there is limited evidence linking selective serotonin reuptake inhibitor use to MS. This study aimed to assess the risk of MS among patients with MDD who were administered vortioxetine and fluoxetine. Methodology This was a prospective, open-label, randomized controlled trial conducted in the psychiatry department. Using computer-generated random numbers, the physician assigned fluoxetine 20 mg or vortioxetine 10 mg and recorded MS parameters at baseline and each visit (4, 8, 12, 16, 20, and 24 weeks). This study was registered with CTRI (CTRI/2021/07/034892). Results A total of 122 participants were allocated randomly to the following two groups: group A (n = 60) and group B (n = 62). An independent-sample t-test showed a significant improvement in fasting plasma glucose (FPG) at week eight (p = 0.005), triglycerides (TGs) at week 16 (p = 0.005), high-density lipoprotein (HDL) at week 20 (p = 0.005), and waist circumference at week 24 (p = 0.005) in group A compared to group B. However, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were not significantly associated with either group (p = 0.126 and p = 0.793, respectively). Overall depression remission (Hamilton Depression Rating Scale (HAM-D)) and medication adherence rating scale scores were similar between groups (p = 0.337 and 0.325, respectively). Furthermore, most adverse drug reactions were possibly associated with the study drugs. Conclusions In comparison to group B, group A showed significant improvements in FPG, HDL, and waist circumference more effectively; however, both groups led to higher TG levels, with non-significant numerical improvements observed in SBP and DBP in both groups. In addition, both treatment groups reduced the HAM-D score and had a similar MDD remission rate.

Serotonergic Medication Error: A Case Report of Serotonin Syndrome.

Serotonin syndrome (SS) describes a life-threatening clinical condition that can develop within hours or days after taking serotonergic medication(s). Medication adverse reactions, overdose, or drug interactions can cause this syndrome. Patients often present with symptoms of hyperthermia, muscle rigidity, hyperreflexia, and clonus. Symptoms range broadly in severity, often influenced by polypharmacy and age. In this report, SS was diagnosed in an elderly patient who presented with diffuse urticaria and exacerbated tremor. These complaints were thought to be associated with Parkinson's disease due to a strong family history. Clinicians are encouraged to consider SS in their differential diagnosis when dealing with elderly patients with multiple medications, psychiatric diagnoses, conditions managed by other providers, and/or a strong family history of neurodegenerative diseases.

A multicenter, randomized controlled study on the efficacy of agomelatine in ameliorating anhedonia, reduced motivation, and circadian rhythm disruptions in patients with major depressive disorder (MDD).

OBJECTIVE: To evaluate the clinical efficacy and safety of Agomelatine in improving symptoms in patients with major depressive disorder (MDD), providing more scientific evidence for the treatment of depression, and offering more effective therapeutic options for patients. METHODS: A total of 180 MDD patients in acute phase from 10 psychiatric hospitals of Grade three in Zhejiang Province were enrolled in this 12-week study with the competitive and consecutive pattern, and they were randomized into two different groups treated with flexible-dosage antidepressants of selective serotonin reuptake inhibitors (SSRI) or agomelatine, respectively. The subjects were evaluated with psychological scales of HAMD-17, HAMA, SHAPS for anhedonia, MFI-20 for fatigue, PQSI for sleep quality and MEQ for disturbances in chronobiologic rhythms at baseline, 2, 4, 8 and 12-weekend points, and TESS was used for side-effect. The results were analyzed with repeated measurement analysis of variance. RESULTS: The two groups each had 90 participants, and there were no significant differences at baseline. The scores of various assessment scales showed statistically significant time main effects during the visits (P < 0.01). The Agomelatine group demonstrated faster efficacy within 2 weeks, with better improvement in SHAPS, MEQ, and PSQI compared to the SSRIs group. However, the remission rate at 12 weeks was lower in the Agomelatine group than in the SSRIs group (63.3% and 72.2%), but the difference between the groups was not statistically significant. The Agomelatine group had fewer adverse reactions (14.4% and 16.7%), but there was a slightly higher incidence of liver function impairment (6.7% and 4.4%), with no statistically significant difference between the groups. CONCLUSION: Agomelatine, as a novel antidepressant, shows certain advantages in improving depression and anxiety symptoms and is comparable to SSRIs in terms of safety. However, its long-term efficacy and safety on MDD or other depressive subtypes still require further observation and research.

Prevalence of Selective Serotonin Reuptake Inhibitor Use Among Pregnant Women From 2017 to 2020 in King Abdulaziz Medical City, Jeddah, Saudi Arabia: A Retrospective Study.

BACKGROUND: Perinatal depression is a mental health disorder that is associated with feelings of hopelessness, despair, and lack of motivation. Its effects on pregnant women are not limited to hemorrhage and hypertension and may lead to maternal mortality. As a result, maternal antidepressant usage during pregnancy has rapidly increased in the United States. Selective serotonin reuptake inhibitors (SSRIs) are considered one of the most prescribed antidepressants. Thus, this study aims to measure the prevalence of SSRI use during pregnancy. METHODS: A retrospective cross-sectional study was carried out in King Abdulaziz Medical City, Jeddah (KAMC-J), Saudi Arabia. The population consisted of all pregnant women aged 18 or older from the period of January 2017 to December 2020 (N=13484). The sampling technique was non-probability consecutive sampling. RESULTS: The study included 13,484 pregnant women, and further analysis revealed that 62 (0.459%) were exposed to at least one type of antidepressant during pregnancy. Of these, 12 (19.35%) had used more than one class of antidepressants. The majority of the sample, comprising 39 (62.90%) women, were between 34 and 44 years old. Furthermore, SSRIs were found to be the most commonly used antidepressant (41, 66.13%). In addition, fluoxetine was the most frequently prescribed antidepressant, with 23 (37.10%) patients receiving this medication. The dosage did not exceed 20 mg for the majority of the patients on SSRIs. CONCLUSION: This study measured the prevalence and patterns of SSRIs and use of different antidepressant classes during pregnancy. After calculating the prevalence of each class of antidepressants among 62 pregnant women exposed to antidepressants, the analysis concluded that SSRIs are the most prescribed antidepressant during pregnancy. This study contributes to the growing body of literature on the use of antidepressants during pregnancy and highlights the need for ongoing research in this area.

Post-traumatic Stress Disorder: A Narrative Review of Pharmacological and Psychotherapeutic Interventions.

Post-traumatic stress disorder (PTSD) is a complex mental health condition affecting individuals exposed to traumatic events. This paper is a narrative review of the existing literature on pharmacological and psychotherapeutic interventions for PTSD. Treatment includes selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and alpha-1 adrenergic receptor antagonists. By exploring the outcomes of these interventions, the review seeks to provide valuable insights into their potential as PTSD treatment options. The paper also highlights the importance of tailoring treatment plans to individual needs and discusses emerging treatments, such as mindfulness-based therapies, virtual reality therapy, and neurostimulation techniques. By integrating findings from various studies, it aims to offer valuable information to optimize treatment strategies and enhance outcomes for individuals suffering from PTSD. The goal is to support informed decision-making, ultimately leading to more effective and tailored approaches to address the challenges posed by this debilitating condition.

Gastrointestinal Symptoms in Pediatric Patients with Anxiety Disorders and Their Relationship to Selective Serotonin Reuptake Inhibitor Treatment or Placebo.

Gastrointestinal symptoms are commonly reported as adverse effects of selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacologic treatment for pediatric anxiety disorders; however, the temporal course of these symptoms during treatment, although believed to be transient, has never been prospectively evaluated. Additionally, rates of gastrointestinal symptoms and functional gastrointestinal syndromes in anxious youth are poorly understood. We examined gastrointestinal symptoms in youth with anxiety disorders during a double-blind, placebo-controlled trial of escitalopram (n = 51). Then, in a separate sample of prospectively treated children and adolescents with generalized, social and/or separation anxiety disorders (n = 56), we examined the frequency of gastrointestinal symptoms based on the Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS) and ROME III criteria and the association of these symptoms with clinical and demographic characteristics using logistic regression. The frequency/severity of abdominal pain, diarrhea, bloating constipation or total gastrointestinal symptoms did not differ between patients receiving placebo (n = 25) or escitalopram (n = 26). However, escitalopram-treated youth had transient changes in nausea/vomiting and total upper gastrointestinal symptoms during the first two weeks of treatment. ROME III criteria for functional gastrointestinal syndromes were present in 12/56 patients (21.4%). QPGS-related functional gastrointestinal syndromes and symptoms were unrelated to treatment, treatment type, or clinical or demographic variables. Gastrointestinal symptoms are common in youth with anxiety and SSRIs produce transient-rather than sustained-gastrointestinal symptoms. Assessing gastrointestinal symptoms prior to pharmacotherapy and discussing factors that increase (or decrease) the likelihood of transient SSRI-related symptoms in youth may decrease patient uncertainty related to side effects and decrease medication-related anxiety.

Review: The use of functional magnetic resonance imaging (fMRI) in clinical trials and experimental research studies for depression.

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that can be used to examine neural responses with and without the use of a functional task. Indeed, fMRI has been used in clinical trials and pharmacological research studies. In mental health, it has been used to identify brain areas linked to specific symptoms but also has the potential to help identify possible treatment targets. Despite fMRI's many advantages, such findings are rarely the primary outcome measure in clinical trials or research studies. This article reviews fMRI studies in depression that sought to assess the efficacy and mechanism of action of compounds with antidepressant effects. Our search results focused on selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed treatments for depression and ketamine, a fast-acting antidepressant treatment. Normalization of amygdala hyperactivity in response to negative emotional stimuli was found to underlie successful treatment response to SSRIs as well as ketamine, indicating a potential common pathway for both conventional and fast-acting antidepressants. Ketamine's rapid antidepressant effects make it a particularly useful compound for studying depression with fMRI; its effects on brain activity and connectivity trended toward normalizing the increases and decreases in brain activity and connectivity associated with depression. These findings highlight the considerable promise of fMRI as a tool for identifying treatment targets in depression. However, additional studies with improved methodology and study design are needed before fMRI findings can be translated into meaningful clinical trial outcomes.

Depression in Patients With Intracranial Hemorrhage Secondary to Traumatic Brain Injury.

This article discusses the prevalence of depression in patients with intracranial hemorrhage (ICH) and the relationship of selective serotonin reuptake inhibitor (SSRI) use with bleeding risk. A detailed account of the patient's psychiatric history and current hospital admission is also provided. This article then further explores the pathophysiological mechanisms that contribute to depression in ICH patients, the effect of SSRIs on outcomes in patients with ICH, and ways to treat depression in ICH patients. Based on the literature, the conclusion is that practitioners should avoid SSRIs in ICH patients with certain genetic markers and treat depression as seriously as one would treat a physical ailment. Ultimately, more research is necessary to explore how to treat depression in this patient population.

Serotonin Syndrome: The Role of Pharmacology in Understanding Its Occurrence.

Serotonin syndrome (SS) is a potentially fatal adverse drug reaction characterized by an exaggerated increase in serotonergic activity in the central and peripheral nervous systems. It presents a constellation of signs and symptoms related to behavioral changes, neuromuscular excitability, and autonomic instability. These symptoms can occur in both mild and severe forms. SS can be triggered by the therapeutic use of a drug that increases serotonin (5-HT) availability in the synaptic cleft or by the co-administration of two or more drugs that provide this increase. With the escalating use of antidepressants by the world's population, this adverse reaction may be more recurrent. However, SS is often overlooked by patients or not diagnosed by doctors. This review aims to improve awareness about SS and provide a pharmacological perspective to explain its occurrence. Evidence shows that other neurotransmitters may also be involved with the pathology of SS. Furthermore, SS and neuroleptic malignant syndrome (NMS) seem to be part of the same pathological spectrum, especially in atypical NMS cases. The emergence of the syndrome's symptoms may be closely related to pharmacokinetic and/or pharmacodynamic polymorphisms that lead to an increase in the 5-HT available to or 5-HT signaling by specific receptors, thus constituting an important area for future investigations.

Prenatal antidepressant exposure and emotional disorders until age 22: a danish register study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressants in pregnancy. Animal and some clinical studies have suggested potential increases in depression and anxiety following prenatal SSRI exposure, but the extent to which these are driven by the medication remains unclear. We used Danish population data to test associations between maternal SSRI use during pregnancy and children outcomes up to age 22. METHODS: We prospectively followed 1,094,202 single-birth Danish children born 1997-2015. The primary exposure was ≥ 1 SSRI prescription filled during pregnancy; the primary outcome, first diagnosis of a depressive, anxiety, or adjustment disorder, or redeemed prescription for an antidepressant medication. We used propensity score weights to adjust potential confounders, and incorporated data from the Danish National Birth Cohort (1997-2003) to further quantify potential residual confounding by subclinical factors. RESULTS: The final dataset included 15,651 exposed and 896,818 unexposed, children. After adjustments, SSRI-exposed had higher rates of the primary outcome than those of mothers who either did not use an SSRI (HR = 1.55 [95%CI:1.44,1.67] or discontinued the SSRI use ≥ 3 months prior to conception (HR = 1.23 [1.13,1.34]). Age of onset was earlier among exposed (9 [IQR:7-13] years) versus unexposed (12 [IQR:12-17] years) children (p < 0.01). Paternal SSRI use in the absence of maternal use during the index pregnancy (HR = 1.46 [1.35,1.58]) and maternal SSRI use only after pregnancy (HR = 1.42 [1.35,1.49]) were each also associated with these outcomes. CONCLUSIONS: While SSRI exposure was associated with increased risk in the children, this risk may be driven at least partly by underlying severity of maternal illness or other confounding factors.

Plasma concentrations of SSRI/SNRI after bariatric surgery and the effects on depressive symptoms.

Background: Depression and treatment with antidepressants SSRI/SNRI are common in people with morbid obesity who are candidates for bariatric surgery. There is few and inconsistent data about the postoperative plasma concentrations of SSRI/SNRI. The aims of our study were to provide comprehensive data about the postoperative bioavailability of SSRI/SNRI, and the clinical effects on depressive symptoms. Methods: Prospective multicenter study including 63 patients with morbid obesity and therapy with fixed doses of SSRI/SNRI: participants filled the Beck Depression Inventory (BDI) questionnaire, and plasma levels of SSRI/SNRI were measured by HPLC, preoperatively (T0), and 4 weeks (T1) and 6 months (T2) postoperatively. Results: The plasma concentrations of SSRI/SNRI dropped significantly in the bariatric surgery group from T0 to T2 by 24.7% (95% confidence interval [CI], -36.8 to -16.6, p = 0.0027): from T0 to T1 by 10.5% (95% 17 CI, -22.7 to -2.3; p = 0.016), and from T1 to T2 by 12.8% (95% CI, -29.3 to 3.5, p = 0.123), respectively.There was no significant change in the BDI score during follow-up (-2.9, 95% CI, -7.4 to 1.0; p = 0.13).The clinical outcome with respect to SSRI/SNRI plasma concentrations, weight change, and change of BDI score were similar in the subgroups undergoing gastric bypass surgery and sleeve gastrectomy, respectively. In the conservative group the plasma concentrations of SSRI/SNRI remained unchanged throughout the 6 months follow-up (-14.7, 95% CI, -32.6 to 1.7; p = 0.076). Conclusion: In patients undergoing bariatric surgery plasma concentrations of SSRI/SNRI decrease significantly by about 25% mainly during the first 4 weeks postoperatively with wide individual variation, but without correlation to the severity of depression or weight loss.

Advances in Pharmacotherapy for Pediatric Anxiety Disorders.

The evidence base for psychopharmacologic interventions in children and adolescents with anxiety disorders has significantly increased, and our understanding of the relative efficacy and tolerability of interventions has expanded contemporaneously. Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacologic treatment for pediatric anxiety due to their robust efficacy although other agents may have efficacy. This review summarizes the data concerning the use of SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, atypical anxiolytics (eg, 5HT1A agonists, alpha agonists), and benzodiazepines in pediatric anxiety disorder cases (ie, generalized anxiety disorder, separation anxiety disorder, social anxiety disorder, and panic disorder). The extant data suggest that SSRIs and SNRIs are effective and well tolerated. SSRIs as monotherapy and SSRIs + cognitive behavioral therapy reduce symptoms in youth with anxiety disorders. However, randomized controlled trials do not suggest efficacy for benzodiazepines or the 5HT1A agonist, buspirone, in pediatric anxiety disorder cases.

Neurobiology of Treatment in Pediatric Anxiety Disorders.

Both pharmacologic and psychotherapeutic treatment-related changes increase activity in brain regions implicated in prefrontal regulatory circuits, and the functional connectivity of these regions with the amygdala is enhanced following pharmacological treatment. This may suggest overlapping mechanisms of action across therapeutic modalities. The existing literature is best viewed as a partially constructed scaffold on which to construct a vigorous understanding of biomarkers in pediatric anxiety syndromes. As the field approaches leveraging "fingerprints" in neuroimaging with "outputs" in neuropsychiatric tasks and scale, we can move beyond one-size-fits-all selection of psychiatric interventions toward more nuanced therapeutic strategies that recognize individual differences.