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BACKGROUND: There is growing evidence for the therapeutic effects of the psychedelic drug psilocybin for major depression. However, due to the lack of safety data on combining psilocybin with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) and concerns that there may be a negative interaction on efficacy, participants enrolling in psychedelic trials are usually required to discontinue SNRI/SNRIs prior to enrolling. AIMS: Using data from a recent clinical trial examining the comparative efficacy the psychedelic drug psilocybin (P) combined with approximately 20 h of psychological support to a 6-week (daily) course of the SSRI escitalopram plus matched psychological support for major depressive disorder, we explored the effects of discontinuing SSRI/SNRIs prior to study enrolment on study outcomes. METHODS: Exploratory post hoc analyses using linear mixed effects model were performed to investigate the discontinuation effect on various validated depression symptom severity scales and well-being. The impact of SSRI/SNRIs discontinuation on the acute psychedelic experience was also explored. RESULTS/OUTCOMES: In the psilocybin group, there was a reduced treatment effect on all outcome measures for SSRI/SNRIs discontinuers compared with unmedicated patients at trial entry. However, no effects of discontinuation on measures of the acute psychedelic experience were found. CONCLUSION: Discontinuation of SSRI/SNRIs before psilocybin might diminish response to treatment; however, as we did not test SSRI/SNRI continuation in our trial, we cannot infer such causation. Moreover, the exploratory nature of the analyses makes them hypothesis generating, and not confirmatory. A controlled trial of SSRI/SNRI discontinuation versus continuation prior to psilocybin is urgently required.

Background: Avoidant/restrictive food intake disorder (ARFID), a DSM-5-introduced eating disorder, is increasingly prevalent and challenging to treat, primarily affecting children and adolescents, with limited adult case reports. This rarity in adults leads to misdiagnosis or underdiagnosis, and treatment experiences are scarce. Case presentation: This report details an adult ARFID case, where the patient's fear of food intake followed gastric damage from corn ingestion, resulting in a restrictive diet of rice porridge due to gastric pain. The behavior is driven by fear of eating-related adverse effects. Result: Based on clinical symptoms assessment, semi-structured interviews, and comprehensive testing, including PET/MRI scans to exclude secondary conditions, a diagnosis of ARFID was confirmed. ARFID, a newly introduced diagnosis in the DSM-5, is uncommon in adults with sparse case data. Differentiating it from gastrointestinal diseases and other psychiatric conditions is crucial for precise diagnosis and focused treatment. Conclusion: In this paper, we report on the clinical diagnosis, imaging manifestations, treatment, and follow-up of an adult ARFID case, highlighting the utility of neuroimaging in diagnosis and differentiation. It also assesses the therapeutic efficacy of olanzapine, escitalopram oxalate, and fluoxetine hydrobromide, offering clinical guidance for diagnosing and managing ARFID. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRI) are the primary treatment for premenstrual mood symptoms and particularly effective in reducing reactive aggression in the forms of irritability and anger. The present study examined whether behavioral responses in laboratory measures of reactive aggression are influenced by medication with the SSRI escitalopram in women reporting high levels of premenstrual irritability/anger. Participants (N = 34) rated the cardinal mood symptoms of premenstrual dysphoric disorder over three menstrual cycles. During the second and third cycles, participants received escitalopram (20 mg) or placebo in a single-blind, cross-over design. In the luteal phase of the intervention cycles, participants completed two aggression tasks: The Anger-Infused Ultimatum Game (AI-UG) and the Point Subtraction Aggression Paradigm (PSAP). Additionally, they rated expression and control of anger using the State-Trait Anger Expression Inventory-2 (STAXI-2) once in the luteal phase and once in the follicular phase. While irritability/anger was reduced in the treatment (vs. placebo) cycle, no effect of escitalopram was detected in the PSAP. Escitalopram decreased reactive aggressive behavior in the AI-UG but only for a subset of participants who experienced a sharp premenstrual rise in outwardly expressed anger and/or did not experience a premenstrual rise in inwardly expressed anger. The participants' symptoms were based on the severity of only premenstrual irritability/anger, limiting the generalizability to the broader group of PMDD patients. The results suggest that the behavioral consequences of severe premenstrual irritability/anger are not easily captured by traditional measures of reactive aggression and underline the importance of considering individual differences in symptom expression. • SSRI efficiently reduces premenstrual irritability/anger. • No differences in aggressive behavior were detected during SSRI (vs placebo). • Individual variations in anger expression may affect SSRI's effect on aggression. [ABSTRACT FROM AUTHOR]

Objectives: Given the unclear etiology and treatment mechanisms of depression, we aim to explore the metabolic differences between patients with major depressive disorder (MDD) and the healthy population, as well as before and after treatment with escitalopram (ESC). Methods: Recruit first-episode drug-naïve MDD (DN-MDD) patients and healthy controls (HCs). Clinical data and serum samples from all subjects were collected at baseline and patients’ samples were collected again after ESC monotherapy for four weeks. Perform non-targeted metabolomic analysis and apply MetaboAnalyst 5.0 to identify differential metabolites and execute KEGG pathway enrichment. Results: Through metabolomic analysis of serum samples, 904 differential metabolites were identified in the DN-MDD group compared to the HCs, and 455 metabolites in treated patients compared to DN-MDD patients. In the pathway analysis, DN-MDD state regulated functions of histidine, beta-alanine, aspartate, and tryptophan metabolism, while ESC treatment produced an influence on the biological process of aspartate and sphingolipid. Conclusion: We respectively depicted metabolism-related biomolecular changes in the serum of patients suffering from MDD and undergoing ESC treatment. Multiple amino acid metabolism pathways were adjusted in MDD patients, and levels of aspartate, arginine and sphingolipids were regulated after ESC monotherapy. These biomolecular changes may bring new insights into the biology and treatment of MDD from the perspective of the serum metabolites. [ABSTRACT FROM AUTHOR]

BACKGROUND: Post natal adaptation syndrome is well reported but early presentation of neurological symptoms severe enough to warrant detailed neurological work up is rare. Our aim was to evaluate and describe abnormal early neurological symptoms in infants following in-utero exposure to a varying combination of selective serotonin uptake inhibitor medication and other psychotropic medications, with negative seizure work-up. METHOD: Descriptive case series of infant exposed to selective serotonin uptake inhibitor medication and other psychotropic medications, presenting with early neurologic signs and symptoms within the first 24 hours of life concerning for seizures, who underwent an extensive neurologic evaluation. RESULTS: Five infants met criteria. Infant #1 : 39-weeks gestational age (GA), with escitalopram, clonazepam, gabapentin, methadone exposure, presented with generalized hypertonia and intermittent back-arching. #2 : 40-weeks GA with escitalopram and hydroxyzine exposure, with bilateral arm stiffening and sucking mouth movements. #3 : 34-weeks GA with fluoxetine, quetiapine and clonazepam exposure, presented with decerebrate posturing. #4 : 38-weeks GA with fluoxetine, clonazepam, clonidine, quetiapine and gabapentin exposure, presented with asynchronous tremoring of all extremities. #5 : 35-weeks GA with citalopram, quetiapine exposure, presented with increased tone and posturing of upper extremities. Electroencephalogram was negative for seizures in all infants. CONCLUSION: In-utero exposure to selective serotonin uptake inhibitor medication, especially in combination with other psychotropic medications, may be associated with significant abnormal neurological symptoms, which may not represent true seizures. [ABSTRACT FROM AUTHOR]

Exposure to chronic stress impairs memory. Also, escitalopram's impact on memory remains paradoxical. Therefore, this study examined how prolonged escitalopram administration affects input-output (I/O) functions, paired-pulse ratio (PPR), and long-term potentiation (LTP) in the hippocampal CA1 area in rats that underwent predictable and unpredictable chronic mild stress (PCMS and UCMS, respectively). Male rats were randomly assigned to different groups of control (Co), sham (Sh), PCMS and UCMS (PSt and USt, respectively; 2 h/day, for 21 consecutive days), escitalopram (Esc; 10 mg/kg, i.p., for 21 days), as well as PCMS and UCMS with escitalopram (PSt-Esc and USt-Esc, respectively). The fEPSP slope, amplitude, and area under the curve (AUC) were assessed in the hippocampal CA1 area using I/O functions, PP responses, and LTP. Serum corticosterone (CORT) levels were quantified in all experimental animals. The slope, amplitude, and AUC of fEPSP in the I/O functions, and all three PP phases prior and subsequent to LTP induction significantly declined in the USt and PSt groups. Escitalopram significantly enhanced these parameters in the PSt-Esc, but not in the USt-Esc group. Serum CORT levels corroborated the electrophysiological findings among experimental groups. Both PCMS and UCMS impaired neural excitability, neurotransmission, and memory within the hippocampal CA1 area. Escitalopram improved memory impairment only under PCMS, potentially attributed to reduced serum CORT levels. However, no influence on neural excitability, neurotransmission, and memory was observed under UCMS. This suggests different escitalopram doses might be required to ameliorate simultaneous mechanisms in response to various types of chronic mild stress. [ABSTRACT FROM AUTHOR]

Chronic stress is a key factor in the development of depression. It leads to hyperactivation of the hypothalamic–pituitary–adrenal (HPA) axis, which in turn increases the formation of glucocorticoids (GCs). Chronically elevated GC levels disrupt neuroplasticity and affect brain lipid metabolism, which may, ultimately, contribute to the development of depression. This study aimed to investigate the effects of the antidepressants St. John's Wort extract and escitalopram on lipid metabolism in vivo. Therefore, repeated corticosterone injections were used to induce depression-like behavior in rats. Male Sprague–Dawley rats were stressed with corticosterone injections (40 mg/kg, s.c.) over 22 consecutive days and were concomitantly treated with varying doses of the St. John's wort extract Ze 117 (30, 90 or 180 mg/kg, p.o.) or escitalopram (10 mg/kg, p.o.) and behavioral changes were evaluated using a modified forced swim test. The results indicate that repeated corticosterone injections significantly decreased the latency to first immobility. Furthermore, co-treatment of corticosterone with Ze 117 increased latency to first immobility significantly compared to rats treated with corticosterone alone. To further investigate the biochemical effects of corticosterone-induced stress, as well as the possible counter-regulation by antidepressants, the lipidomes of the plasma and hippocampus samples were analyzed by shotgun mass spectrometry. Corticosterone-induced stress significantly altered key lipid metabolites in the plasma but not in the hippocampal samples. In the hippocampus, however, specific glycerophospholipids such as lysophosphatidylethanolamines (LPEs) increased with escitalopram treatment and with Ze 117, both showing significant correlations with behavioral parameters. In summary, our study shows significant behavioral- and lipidome-altering processes with Ze 117 and escitalopram in rat plasma and hippocampal samples, thereby providing new targets and biomarker ideas for clinical diagnosis and antidepressant intervention. [ABSTRACT FROM AUTHOR]