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Frontiers in Pharmacology 2024Esketamine nasal spray (ESK-NS) is a new drug for treatment-resistant depression, and we aimed to detect and characterize the adverse events (AEs) of ESK-NS using the...
Esketamine nasal spray (ESK-NS) is a new drug for treatment-resistant depression, and we aimed to detect and characterize the adverse events (AEs) of ESK-NS using the Food and Drug Administration (FDA) adverse event reporting system (FAERS) database between 2019 Q1 and 2023 Q4. Reporting odds ratio (ROR), proportional reporting ratio (PRR), and multi-item gamma Poisson shrinker (MGPS) were performed to detect risk signals from the FAERS data to identify potential ESK-NS-AEs associations. A total of 14,606 reports on AEs with ESK-NS as the primary suspected drug were analyzed. A total of 518 preferred terms signals and 25 system organ classes mainly concentrated in psychiatric disorders (33.20%), nervous system disorders (16.67%), general disorders and administration site conditions (14.21%), and others were obtained. Notably, dissociation ( = 1,093, ROR 2,257.80, PRR 899.64, EBGM 876.86) exhibited highest occurrence rates and signal intensity. Moreover, uncommon but significantly strong AEs signals, such as hand-eye coordination impaired, feeling guilty, and feelings of worthlessness, were observed. Additionally, dissociative disorder ( = 57, ROR 510.92, PRR 506.70, EBGM 386.60) and sedation ( = 688, ROR 172.68, PRR 155.53, and EBGM 142.05) both presented strong AE signals, and the former is not recorded in the Summary of Product Characteristics (SmPC). In clinical applications, close attention should be paid to the psychiatric disorders and nervous system disorders, especially dissociation. Meanwhile, clinical professionals should be alert for the occurrence of AEs signals not mentioned in the SmPC and take preventive measures to ensure the safety of clinical use.
PubMed: 38948465
DOI: 10.3389/fphar.2024.1414703 -
Brain Sciences Jun 2024Glucagon-like peptide-1 (GLP-1) is involved in a range of central and peripheral pathways related to appetitive behavior. Hence, this study explored the effects of...
Glucagon-like peptide-1 (GLP-1) is involved in a range of central and peripheral pathways related to appetitive behavior. Hence, this study explored the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on substance and behavioral addictions, including alcohol, caffeine, nicotine, cannabis, psychostimulants, compulsive shopping, and sex drive/libido. Data were collected from various social platforms. Keywords related to GLP-1 RAs and substance/behavioral addiction were used to extract relevant comments. The study employed a mixed-methods approach to analyze online discussions posted from December 2019 to June 2023 and collected using a specialized web application. Reddit entries were the focus here due to limited data from other platforms, such as TikTok and YouTube. A total of 5859 threads and related comments were extracted from six subreddits, which included threads about GLP-1 RAs drugs and associated brand names. To obtain relevant posts, keywords related to potential substance use and compulsive behavior were selected. Further analysis involved two main steps: (1) manually coding posts based on users' references to the potential impact of GLP-1 RAs on substance use and non-substance habits, excluding irrelevant or unclear comments; (2) performing a thematic analysis on the dataset of keywords, using AI-assisted techniques followed by the manual revision of the generated themes. Second, a thematic analysis was performed on the keyword-related dataset, using AI-assisted techniques followed by the manual revision of the generated themes. In total, 29.75% of alcohol-related; 22.22% of caffeine-related; and 23.08% of nicotine-related comments clearly stated a cessation of the intake of these substances following the start of GLP-1 RAs prescription. Conversely, mixed results were found for cannabis intake, and only limited, anecdotal data were made available for cocaine, entactogens, and dissociative drugs' misuse. Regarding behavioral addictions, 21.35% of comments reported a compulsive shopping interruption, whilst the sexual drive/libido elements reportedly increased in several users. The current mixed-methods approach appeared to be a useful tool in gaining insight into complex topics such as the effects of GLP-1 RAs on substance and non-substance addiction-related disorders; some GLP-1 RA-related mental health benefits could also be inferred from here. Overall, it appeared that GLP-1 RAs may show the potential to target both substance craving and maladaptive/addictive behaviors, although further empirical research is needed.
PubMed: 38928616
DOI: 10.3390/brainsci14060617 -
International Journal of Molecular... Jun 2024NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative diseases, epilepsy, traumatic brain... (Review)
Review
NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative diseases, epilepsy, traumatic brain injury, substance abuse disorder (SUD), and major depressive disorder (MDD). ()-ketamine was the first of a novel class of antidepressants, rapid-acting antidepressants, to be approved for medical use. The stereoisomer, ()-ketamine (arketamine), is currently under development for treatment-resistant depression (TRD). The compound has demonstrated efficacy in multiple animal models. Two clinical studies disclosed efficacy in TRD and bipolar depression. A study by the drug sponsor recently failed to reach a priori clinical endpoints but post hoc analysis revealed efficacy. The clinical value of ()-ketamine is supported by experimental data in humans and rodents, showing that it is less sedating, does not produce marked psychotomimetic or dissociative effects, has less abuse potential than ()-ketamine, and produces efficacy in animal models of a range of neurological and psychiatric disorders. The mechanisms of action of the antidepressant effects of ()-ketamine are hypothesized to be due to NMDA receptor antagonism and/or non-NMDA receptor mechanisms. We suggest that further clinical experimentation with ()-ketamine will create novel and improved medicines for some of the neurological and psychiatric disorders that are underserved by current medications.
Topics: Ketamine; Humans; Animals; Antidepressive Agents; Nervous System Diseases; Receptors, N-Methyl-D-Aspartate; Mental Disorders; Stereoisomerism
PubMed: 38928508
DOI: 10.3390/ijms25126804 -
Cureus May 2024Dissociative identity disorder (DID), previously recognized as multiple personality disorder, impacts approximately 1.5% of the population. The Diagnostic and...
Dissociative identity disorder (DID), previously recognized as multiple personality disorder, impacts approximately 1.5% of the population. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), outlines various dissociative disorders (DDs), including depersonalization/derealization disorder, dissociative amnesia, DID, unspecified DD, and other specified DDs. Among these, DID stands out as the most severe, characterized by persistent depersonalization/derealization and dissociative amnesia. This case report explores the symptomatology of DID, available treatments, and the role of trauma.
PubMed: 38899275
DOI: 10.7759/cureus.60676 -
The International Journal of... Jun 2024
Topics: Ketamine; Humans; Dissociative Disorders; Depression; Excitatory Amino Acid Antagonists; Antidepressive Agents
PubMed: 38864154
DOI: 10.1093/ijnp/pyae024 -
BMJ Neurology Open 2024The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures multicentre randomised controlled trial is the... (Review)
Review
The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures multicentre randomised controlled trial is the largest, fully-powered study to test the clinical and cost-effectiveness of a psychotherapeutic intervention in this population. We also explored predictors or moderators of outcomes and investigated mechanisms of change in therapy. In this current review of findings, we discuss issues related to the design of the trial and consider the study's nested qualitative studies which were undertaken not only to shed light on the original research questions but to provide insights and recommendations for other researchers in the field of functional neurological disorder. Finally, we consider issues relating to the possible clinical application of our study findings.
PubMed: 38860230
DOI: 10.1136/bmjno-2024-000659 -
BMJ Neurology Open 2024Dissociative seizures often occur in the context of dysregulated affective arousal and entail dissociative symptoms such as a disintegration of bodily awareness....
INTRODUCTION
Dissociative seizures often occur in the context of dysregulated affective arousal and entail dissociative symptoms such as a disintegration of bodily awareness. However, the interplay between affective arousal and changes in interoceptive processing at the onset of dissociative seizures is not well understood.
METHODS
Using retrospective routine data obtained from video-electroencephalography telemetry in a university hospital epilepsy monitoring unit, we investigate ictal changes in cardiac indices of autonomic arousal and heartbeat evoked potentials (HEPs) in 24 patients with dissociative seizures.
RESULTS
Results show autonomic arousal during seizures with increased heart rate and a shift towards sympathetic activity. Compared with baseline, ictal HEP amplitudes over central and right prefrontal electrodes (F8, Fz) were significantly less pronounced during seizures, suggesting diminished cortical representation of interoceptive information. Significant correlations between heart rate variability measures and HEPs were observed at baseline, with more sympathetic and less parasympathetic activity related to less pronounced HEPs. Interestingly, these relationships weakened during seizures, suggesting a disintegration of autonomic arousal and interoceptive processing during dissociative seizures. In a subgroup of 16 patients, MRI-based cortical thickness analysis found a correlation with HEP amplitudes in the left somatosensory association cortex.
CONCLUSIONS
These findings possibly represent an electrophysiological hint of how autonomic arousal could negatively impact bodily awareness in dissociative seizures, and how these processes might be related to underlying brain structure.
PubMed: 38860229
DOI: 10.1136/bmjno-2024-000665 -
Bioinformation 2024The role of lacosamide (LCM) as add on treatment modality in dissociative disorders (DD) is of interest. It was a randomized control trial in which 300 patients...
The role of lacosamide (LCM) as add on treatment modality in dissociative disorders (DD) is of interest. It was a randomized control trial in which 300 patients diagnosed with dissociative disorders having treatment for the dissociative disorders were included. They were divided into two groups. Group one consisted of intervention group in which LCM was also administered along with conventional psychiatric medication for different dissociative disorders. Group two consisted of control group where the patients of dissociative disorders were found to have conventional medication. There was analysis of improvements in recovery of symptoms and quality of life. There was statistically significant increase in excellent, very good, good and fair quality of life and decrease in poor and satisfactory quality of life in intervention group after drug intervention. It was observed that symptoms of the patients improved in 50.67% cases in intervention group and 10.67% cases in control group. There was greater improvement in recovery of symptoms and quality of life in patients of DD in which LCM was administered as add on medication.
PubMed: 38854771
DOI: 10.6026/973206300200373 -
Medical Science Monitor : International... Jun 2024Daydreaming, a form of spontaneous and self-generated mental process, may lead to the disintegration of attention from the immediate external environment. In extreme... (Review)
Review
Daydreaming, a form of spontaneous and self-generated mental process, may lead to the disintegration of attention from the immediate external environment. In extreme cases, patients may develop maladaptive daydreaming comorbid with dissociation. The examination of dissociative alterations frequently occurs within the framework of complex cognitive processes. While dissociation may be a neurological and psychological dysfunction of integration, transient dissociative occurrences, i.e., momentary dissociation may signify a dynamic interplay between attentional division and orientation within the sensory cortex. Furthermore, previous studies have recorded the interactivity of attention by stimuli onset with P3 event-related potentials and the active suppression of distractor positivity. In this context, during auditory and visual mismatch negativity, the sensory cortex may interact with attentional orientation. Additionally, distractor positivity during task-relevant stimuli may play a crucial role in predicting momentary dissociation since sensory cortices share cerebral correlates with attentional fluctuations during mental imagery. Thus, this theoretical review investigated the cerebral activities associated with attentional orientation and may be extended to mindfulness. By integrating these findings, we aim to provide a comprehensive understanding of dissociative states which may lead to a resolution for dissociative psychopathology.
Topics: Humans; Attention; Dissociative Disorders; Electroencephalography; Evoked Potentials
PubMed: 38848281
DOI: 10.12659/MSM.944209 -
Seizure Jul 2024Psychological interventions are the most recommended treatment for functional/dissociative seizures (FDS); however, there is ongoing uncertainty about their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psychological interventions are the most recommended treatment for functional/dissociative seizures (FDS); however, there is ongoing uncertainty about their effectiveness on seizure outcomes.
METHODS
This systematic review and meta-analysis synthesises the available data. In February 2023, we completed a systematic search of four electronic databases. We described the range of seizure-related outcomes captured, used meta-analytic methods to analyse data collected during treatment and follow-up; and explored sources of heterogeneity between outcomes.
RESULTS
Overall, 44 relevant studies were identified involving 1,300 patients. Most were categorised as being at high (39.5 %) or medium (41.9 %) risk of bias. Seizure frequency was examined in all but one study; seizure intensity, severity or bothersomeness in ten; and seizure duration and cluster in one study each. Meta-analyses could be performed on seizure freedom and seizure reduction. A pooled estimate for seizure freedom at the end of treatment was 40 %, while for follow-up it was 36 %. Pooled rates for ≥50 % improvement in seizure frequency were 66 % and 75 %. None of the included moderator variables for seizure freedom were significant. At the group level, seizure frequency improved during the treatment phase with a moderate pooled effect size (d = 0.53). FDS frequency reduced by a median of 6.5 seizures per month. There was also evidence of improvement of the other (non-frequency) seizure-related measures with psychological therapy, but data were insufficient for meta-analysis.
CONCLUSIONS
The findings of this study complement a previous meta-analysis describing psychological treatment-associated improvements in non-seizure-related outcomes. Further research on the most appropriate FDS-severity measure is needed.
Topics: Adult; Humans; Dissociative Disorders; Psychotherapy; Seizures; Treatment Outcome
PubMed: 38824867
DOI: 10.1016/j.seizure.2024.05.016