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Harvard Review of PsychiatryFirst-line treatment for obsessive-compulsive disorder (OCD) includes exposure and response prevention behavioral therapy and serotonin reuptake inhibitors, particularly...
INTRODUCTION
First-line treatment for obsessive-compulsive disorder (OCD) includes exposure and response prevention behavioral therapy and serotonin reuptake inhibitors, particularly in combination. New and more effective treatments are needed, give that recent studies suggest that glutamatergic neurotransmission contributes to the pathophysiology of the disorder. In these circumstances, ketamine, as a potent N-methyl-D-aspartate receptor antagonist and glutamate modulator, offers alternative possibilities for OCD treatment.
METHODS
This systematic review aims to investigate the effects of ketamine in OCD, following the Preferred Reporting Items for Systematic Review and Meta-analyses Protocols (PRISMA-P). Searches were carried out using the PubMed/MEDLINE, Embase, and PsycINFO databases.
RESULTS
Nine articles were included, of which three were randomized controlled trials, three case reports, two open-label trials, and one a retrospective chart review. Reported data have shown a potential for fast onset of action and good tolerability of ketamine for OCD, even though the principal studies used only single-session racemic ketamine treatments, administered intravenously, and the results have been erratic. In addition, none of the available evidence demonstrates whether racemic ketamine, S-ketamine, or R-ketamine has the best efficacy in controlling OCD symptoms, and only sparse evidence suggests that a combination of ketamine and psychotherapy could benefit patients with OCD.
CONCLUSION
In order to advance clinical practice regarding the use of ketamine in treating OCD, future randomized, double-blind, placebo-controlled trials are required. These trials need to use larger samples to explore ketamine and its enantiomers, with different methods of administration, multiple sessions, and appropriate washout periods.
Topics: Humans; Ketamine; Obsessive-Compulsive Disorder; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 35267254
DOI: 10.1097/HRP.0000000000000330 -
Psychiatry Research Oct 2021Robust evidence suggests that depression, and risk for depression, are associated with the generation of stressful life events. This tendency to generate stress may be... (Review)
Review
AIM
Robust evidence suggests that depression, and risk for depression, are associated with the generation of stressful life events. This tendency to generate stress may be genetically determined. This systematic review aimed to identify specific molecular genetic markers associated with the generation of interpersonal stressful life events, at least in part dependent on individuals' behavior.
METHOD
We followed the PRISMA guidelines in searching six electronic databases (PubMed, MEDLINE, PsycINFO, CINAHL, Cochrane, and EMBASE) from inception to January 2021, and we reviewed the reference lists of eligible articles for additional records. We restricted eligibility to empirical studies involving at least one genetic marker and including proximal life events. We evaluated the risk of bias using the Newcastle Ottawa Scale for observational studies. The outcome permitted a distinction between life events dependent on the individual's agency versus independent events.
RESULTS
Seven studies, including 3585 participants, met eligibility criteria. Three were longitudinal, and four were cross-sectional; six included adolescents and young adults, and one focused on middle adulthood. Four examined the serotonin-transporter-linked promoter region (5-HTTLPR), two examined the rs53576 single nucleotide polymorphism of the oxytocin receptor gene (OXTR), and one examined a multilocus genetic profile score including four hypothalamic-pituitary-adrenal (HPA) axis genes. There were no significant direct correlations between genotype and life events in any study. Instead, their relation was significantly moderated by symptoms, exposure to early adversity, or attachment. Consistent with the stress generation hypothesis, this moderation relation was significant in predicting exposure to dependent life events but was not significant in predicting independent life event exposure.
CONCLUSIONS
There is evidence that genetic variation in the serotonin, HPA axis, and oxytocin systems moderates the effects of psychosocial vulnerability markers on the generation of proximal, dependent life events. Future research should examine additional genetic markers in systems known to confer risk for stress generation.
PROSPERO
CRD42019136886.
Topics: Adolescent; Adult; Cross-Sectional Studies; Genetic Markers; Genotype; Humans; Hypothalamo-Hypophyseal System; Life Change Events; Pituitary-Adrenal System; Serotonin Plasma Membrane Transport Proteins; Stress, Psychological; Young Adult
PubMed: 34371296
DOI: 10.1016/j.psychres.2021.114139 -
European Journal of Pain (London,... Apr 2022Evidence for perioperative methods to prevent persistent postsurgical pain (PPP) is uncertain, in part because few treatments have been directly compared. Here we have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Evidence for perioperative methods to prevent persistent postsurgical pain (PPP) is uncertain, in part because few treatments have been directly compared. Here we have used component network meta-analysis (cNMA) to incorporate both direct and indirect evidence in the evaluation of the efficacy and tolerability of pharmacological and neural block treatments.
DATABASES AND DATA TREATMENT
We searched the Cochrane Central Registry of Controlled Trials, Embase, MEDLINE, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry up to January 2021 for randomized, double-masked, controlled trials that reported the prevalence of PPP. We assessed trial quality with the Cochrane risk of bias tool (RoB 2.0). We analysed the results with frequentist cNMA models. The primary outcome was the relative risk (RR) of PPP. We assessed efficacy in relation to a clinically important effect size of RR = 0.9, which is a 10% improvement with treatment.
RESULTS
The analysis included 107 trials (13,553 participants) of 13 treatments. The effects of complex interventions were the multiplicative effects of their components. Compared with placebo, serotonin-norepinephrine reuptake inhibitors (SNRIs), neural block alone, or in combination with NMDA receptor blockers or gabapentanoids were effective. Treatments with benefit in the immediate post-operative period predicted a reduced risk of PPP.
CONCLUSIONS
Several treatments and treatment combinations effectively reduce PPP prevalence. Pain outcomes in the immediate postoperative period are an important mediator of PPP. Multimodal interventions can be analysed using cNMA.
SIGNIFICANCE
Systematic reviews of PPP prevention usually focus on the efficacy of specific treatments in comparison with control interventions. In this study we used component network meta-analysis to compare interventions to each other, including both pharmacological and neural block techniques, and multimodal interventions. Interventions that are not effective alone may improve the efficacy of multimodal interventions that include neural block techniques. Immediate postoperative benefit was an important mediator for reduction of PPP.
STUDY REGISTRATION
PROSPERO: CRD42018085570 https://www.crd.york.ac.uk/prospero/.
Topics: Humans; Nerve Block; Network Meta-Analysis; Pain, Postoperative; Selective Serotonin Reuptake Inhibitors
PubMed: 35090077
DOI: 10.1002/ejp.1915 -
Acta Gastro-enterologica Belgica 2021Intestinal pseudo obstruction both acute and chronic is an uncommon severe motility disorder that affect both children and adults, can lead to significant morbidity... (Review)
Review
BACKGROUND
Intestinal pseudo obstruction both acute and chronic is an uncommon severe motility disorder that affect both children and adults, can lead to significant morbidity burden and have no standard management strategy. Prucalopride a highly selective serotonin receptor agonist is an effective laxative with reported extra colon action. We aim to report our experience in children with acute and chronic intestinal pseudo obstruction who responded to prucalopride and systemically review the use of prucalopride in intestinal pseudo obstruction.
METHODS
A report of clinical experience and systemic review of the relevant medical databases to identify the outcome of usage of prucalopride in patients with acute and chronic intestinal pseudo obstruction. Studies meeting the selection criteria were reviewed including abstract only and case reports.
RESULTS
All reported cases showed clinical response to prucalopride. There were three full text, two abstracts only and three case reports all reporting clinical improvement with prucalopride.
CONCLUSION
Prucalopride appears to show promising results in children and adults with acute and chronic intestinal pseudo obstruction.
Topics: Adult; Benzofurans; Child; Colon; Humans; Intestinal Pseudo-Obstruction; Laxatives
PubMed: 34599567
DOI: 10.51821/84.3.002 -
Cureus Apr 2023Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that affects approximately 2% of the human population. Traditional treatment of OCD includes selective... (Review)
Review
Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that affects approximately 2% of the human population. Traditional treatment of OCD includes selective serotonin reuptake inhibitor (SSRI) or serotonin reuptake inhibitor (SRI) treatment along with cognitive behavioral therapy (CBT). Nearly 25%-30% of OCD patients do not respond to SSRIs. Glutamatergic agents are currently being studied for the treatment of OCD due to the glutamatergic pathway in the brain, related to OCD, and the role of the cortico-striato-thalamic circuit (CSTC). This review assesses the clinical effectiveness of N-methyl-D-aspartate (NMDA) antagonists, ketamine/esketamine, memantine, and amantadine, for adult patients with OCD. Inclusion criteria include human studies published within the last 15 years, with patients diagnosed with OCD, aged over 18 years, with only psychiatric comorbidities, and full-text articles. Papers that included interventions other than CBT, exposure with response prevention (ERP), and SSRI/SRI were excluded. Articles were searched for using PubMed, PubMed Central, Medical Literature Analysis and Retrieval System Online, GeorgiA LIbrary LEarning Online, EBSCO Information Services, OpenAthens, Multidisciplinary Digital Publishing Institute, and Google Scholar databases, last searched on December 2, 2022. The risk of bias was assessed using Cochrane Risk of Bias tools, the Scale for the Assessment of Narrative Review Articles (SANRA) checklist for literature reviews, and the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for quasi-experimental studies. Results were presented and synthesized by Excel spreadsheet analysis. The database search yielded 4,221 articles, which was cut down to 18 articles by inclusion/exclusion criteria, including duplications. 80% of the ketamine studies resulted in a significant reduction of obsessions and compulsions based on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and each of the memantine and amantadine studies displayed clinical effectiveness, also. Limitations include the small number of amantadine studies and the limited availability of other NMDA receptor (NMDAR) antagonist-focused studies. This systematic review shows that ketamine is an effective drug for the treatment of non-refractory, mild to moderate OCD, and memantine and amantadine are effective augmentation agents for the treatment of mild to severe OCD.
PubMed: 37213965
DOI: 10.7759/cureus.37833 -
Schizophrenia Research. Cognition Dec 2023In a previous meta-analysis, the use of serotonin(5-HT) receptor partial agonists of the azapirone class as an add-on therapy was associated with beneficial effects on...
BACKGROUND
In a previous meta-analysis, the use of serotonin(5-HT) receptor partial agonists of the azapirone class as an add-on therapy was associated with beneficial effects on positive symptoms and attention/processing speed in schizophrenia patients. This meta-analysis builds on that study by examining the effects of adjunctive treatment with 5-HT partial agonists in improving other domains of neurocognitive function in schizophrenia patients.
METHODS
A literature search was performed from 1987 to May 2023 to identify randomized controlled trials. The standardized mean difference (SMD) with 95 % confidence intervals (CI) was calculated when there were two or more studies. Four studies, involving 313 patients, met the inclusion criteria and were used in the analysis.
RESULTS
5-HT partial agonists (buspirone or tandospirone) did not have a significant effect on verbal learning (SMD = 0.08, 95 % CI = -0.31 to 0.47) or working memory (SMD = 0.15, 95 % CI = -0.09 to 0.39). Regarding executive functions (Wisconsin Card Sorting Test), positive but non-significant results were seen with the category number (SMD = 0.26, 95 % CI = -0.81 to 1.32), while non-significant effects were noted for percent preservation errors (SMD = -0.10, 95 % CI = -0.53 to 0.33).
CONCLUSIONS
The absence of any significant benefits in the cognitive domains studied here may have been due to the variance in the concomitant medication (typical vs atypical antipsychotic drugs), the level of cognition at baseline, or other factors. Further studies with various types of 5-HT agonists are warranted to examine the potential cognitive efficacy of stimulating these receptors.
PubMed: 37732133
DOI: 10.1016/j.scog.2023.100290 -
Progress in Neuro-psychopharmacology &... Dec 2020Global reports estimate the number of betel quid (BQ) chewers up to 600 million. The proportion of betel quid dependence (BQD) is 20%-90% among current users. BQD...
BACKGROUND
Global reports estimate the number of betel quid (BQ) chewers up to 600 million. The proportion of betel quid dependence (BQD) is 20%-90% among current users. BQD mechanisms are not fully understood, and no pharmacological solution exists for its cessation therapy.
METHODS
We present a systematic review on BQD mechanisms and examine potential cessation therapeutic drugs. We conducted a systematic literature search in PubMed and Web of Science databases and identified the latest 10 years' relevant articles for reviews.
RESULTS
Functional magnetic resonance imaging results demonstrate that neurological mechanisms link the brain reward, cognitive, and impulsive systems in BQ or BQD users. The use of the areca nut increases both brain serotonin and noradrenaline levels, whereas arecoline, a potentially addictive areca nut component, has monoamine oxidase-A (MAO-A) inhibitor-like properties. MAO-A inhibitors prevent neurotransmitter breakdown and increase dopamine and serotonin concentrations in the brain. A reduction of daily BQ use was observed among patients with depression after antidepressant therapy, including MAO-A inhibitor and selective serotonin reuptake inhibitor (SSRI). Arecoline is a nicotinic acetylcholine receptor agonist expressed in Xenopus oocytes. However, relatively negligible amounts of nicotine are detected in the areca nut.
CONCLUSION
In conclusion, the current evidence provides a better understanding of the neurological and pharmacological mechanisms behind BQD. Arecoline, an MAO-A inhibitor, may account for BQD. Future translational studies are needed to verify the efficacy of potential BQD cessation drugs. MAO-A inhibitor and SSRI would thus be potentially promising targets for clinical trials.
Topics: Animals; Areca; Arecoline; Behavior, Addictive; Brain Chemistry; Humans; Magnetic Resonance Imaging; Monoamine Oxidase Inhibitors; Substance-Related Disorders
PubMed: 32454163
DOI: 10.1016/j.pnpbp.2020.109982 -
Nutrients Jun 2023Evidence is emerging for the role of intestinal tryptophan metabolism in the development of inflammatory bowel disease (IBD). In order to identify the role of altered... (Meta-Analysis)
Meta-Analysis Review
The Involvement of Intestinal Tryptophan Metabolism in Inflammatory Bowel Disease Identified by a Meta-Analysis of the Transcriptome and a Systematic Review of the Metabolome.
Evidence is emerging for the role of intestinal tryptophan metabolism in the development of inflammatory bowel disease (IBD). In order to identify the role of altered intestinal tryptophan metabolism in IBD pathogenesis, a meta-analysis of the transcriptome was performed to identify differentially expressed genes involved in the tryptophan metabolism pathways in intestinal biopsies of IBD as compared to non-IBD controls. Moreover, a systematic review of the metabolome was performed to identify the concurrent changes in tryptophan metabolites. Integration of the transcriptome and metabolome identified various alterations in intestinal tryptophan metabolism during active disease in IBD patients, including decreased intestinal tryptophan absorption, enhanced kynurenine pathway, increased interstitial serotonin availability, changed indole pathway, and activated aryl hydrocarbon receptor signaling. Therefore, a network of intestinal tryptophan metabolism pathways in IBD could be established, helping to assess the potential of genes and metabolites involved in these pathways as diagnostic markers and targets for IBD management.
Topics: Humans; Tryptophan; Transcriptome; Inflammatory Bowel Diseases; Intestines; Metabolome
PubMed: 37447212
DOI: 10.3390/nu15132886 -
Epilepsy & Behavior : E&B Feb 2021Depression is a relatively common comorbidity in people with epilepsy with a lifetime history identified in 1 in 4 individuals. In this paper, we aimed to provide a... (Review)
Review
OBJECTIVE
Depression is a relatively common comorbidity in people with epilepsy with a lifetime history identified in 1 in 4 individuals. In this paper, we aimed to provide a systematic review of structural and functional brain region-specific group differences of adults with epilepsy and depression and to discuss existing evidence as compared to that in people with depression.
METHODS
We undertook a systematic review of neuroimaging studies of depression in adults with epilepsy through MEDLINE/PubMed, Embase and PsycInfo searches until June 2020.
RESULTS
A total of 44 studies were included in the qualitative synthesis: 21 on structural neuroimaging, 9 on functional, and 14 on pharmaco/metabolic neuroimaging. Almost all studies focused on temporal lobe epilepsy (TLE). Patterns of changes in the hippocampi and subcortical structures seem to be different from those reported in depression outside epilepsy. Cortical changes are grossly similar as well as the lack of any laterality effect. Serotonin dysfunction seems to be due to different mechanisms with reduced synaptic availability for depression in epilepsy as compared to reduced 5HT1 receptor density outside epilepsy. Depressive symptoms seem to correlate with a dysfunction in temporolimbic structures contralateral to the epileptogenic zone especially in patients with de novo postsurgical depression.
CONCLUSIONS
Depression, at least in TLE, seems to be associated with a different pattern of brain changes as compared to major depression, potentially supporting the notion of phenomenological peculiarities of depression in epilepsy.
Topics: Adult; Depression; Epilepsy; Epilepsy, Temporal Lobe; Hippocampus; Humans; Magnetic Resonance Imaging; Neuroimaging
PubMed: 33348194
DOI: 10.1016/j.yebeh.2020.107695 -
CNS Spectrums Apr 2022Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral... (Review)
Review
BACKGROUND
Blood platelets, due to shared biochemical and functional properties with presynaptic serotonergic neurons, constituted, over the years, an attractive peripheral biomarker of neuronal activity. Therefore, the literature strongly focused on the investigation of eventual structural and functional platelet abnormalities in neuropsychiatric disorders, particularly in depressive disorder. Given their impact in biological psychiatry, the goal of the present paper was to review and critically analyze studies exploring platelet activity, functionality, and morpho-structure in subjects with depressive disorder.
METHODS
According to the PRISMA guidelines, we performed a systematic review through the PubMed database up to March 2020 with the search terms: (1) platelets in depression [Title/Abstract]"; (2) "(platelets[Title]) AND depressive disorder[Title/Abstract]"; (3) "(Platelet[Title]) AND major depressive disorder[Title]"; (4) (platelets[Title]) AND depressed[Title]"; (5) (platelets[Title]) AND depressive episode[Title]"; (6) (platelets[Title]) AND major depression[Title]"; (7) platelet activation in depression[All fields]"; and (8) platelet reactivity in depression[All fields]."
RESULTS
After a detailed screening analysis and the application of specific selection criteria, we included in our review a total of 106 for qualitative synthesis. The studies were classified into various subparagraphs according to platelet characteristics analyzed: serotonergic system (5-HT2A receptors, SERT activity, and 5-HT content), adrenergic system, MAO activity, biomarkers of activation, responsivity, morphological changes, and other molecular pathways.
CONCLUSIONS
Despite the large amount of the literature examined, nonunivocal and, occasionally, conflicting results emerged. However, the findings on structural and metabolic alterations, modifications in the expression of specific proteins, changes in the aggregability, or in the responsivity to different pro-activating stimuli, may be suggestive of potential platelet dysfunctions in depressed subjects, which would result in a kind of hyperreactive state. This condition could potentially lead to an increased cardiovascular risk. In line with this hypothesis, we speculated that antidepressant treatments would seem to reduce this hyperreactivity while representing a potential tool for reducing cardiovascular risk in depressed patients and, maybe, in other neuropsychiatric conditions. However, the problem of the specificity of platelet biomarkers is still at issue and would deserve to be deepened in future studies.
Topics: Antidepressive Agents; Biomarkers; Blood Platelets; Depressive Disorder, Major; Humans; Serotonin
PubMed: 33092669
DOI: 10.1017/S1092852920001959