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JAMA Psychiatry Dec 2022Whether ketamine is as effective as electroconvulsive therapy (ECT) among patients with major depressive episode remains unknown. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Whether ketamine is as effective as electroconvulsive therapy (ECT) among patients with major depressive episode remains unknown.
OBJECTIVE
To systematically review and meta-analyze data about clinical efficacy and safety for ketamine and ECT in patients with major depressive episode.
DATA SOURCES
PubMed, MEDLINE, Cochrane Library, and Embase were systematically searched using Medical Subject Headings (MeSH) terms and text keywords from database inception through April 19, 2022, with no language limits. Two authors also manually and independently searched all relevant studies in US and European clinical trial registries and Google Scholar.
STUDY SELECTION
Included were studies that involved (1) a diagnosis of depression using standardized diagnostic criteria, (2) intervention/comparator groups consisting of ECT and ketamine, and (3) depressive symptoms as an efficacy outcome using standardized measures.
DATA EXTRACTION AND SYNTHESIS
Data extraction was completed independently by 2 extractors and cross-checked for errors. Hedges g standardized mean differences (SMDs) were used for improvement in depressive symptoms. SMDs with corresponding 95% CIs were estimated using fixed- or random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed.
MAIN OUTCOMES AND MEASURES
Efficacy outcomes included depression severity, cognition, and memory performance. Safety outcomes included serious adverse events (eg, suicide attempts and deaths) and other adverse events.
RESULTS
Six clinical trials comprising 340 patients (n = 162 for ECT and n = 178 for ketamine) were included in the review. Six of 6 studies enrolled patients who were eligible to receive ECT, 6 studies were conducted in inpatient settings, and 5 studies were randomized clinical trials. The overall pooled SMD for depression symptoms for ECT when compared with ketamine was -0.69 (95% CI, -0.89 to -0.48; Cochran Q, P = .15; I2 = 39%), suggesting an efficacy advantage for ECT compared with ketamine for depression severity. Significant differences were not observed between groups for studies that assessed cognition/memory or serious adverse events. Both ketamine and ECT had unique adverse effect profiles (ie, ketamine: lower risks for headache and muscle pain; ECT: lower risks for blurred vision, vertigo, diplopia/nystagmus, and transient dissociative/depersonalization symptoms). Limitations included low to moderate methodological quality and underpowered study designs.
CONCLUSIONS AND RELEVANCE
Findings from this systematic review and meta-analysis suggest that ECT may be superior to ketamine for improving depression severity in the acute phase, but treatment options should be individualized and patient-centered.
Topics: Humans; Electroconvulsive Therapy; Ketamine; Depressive Disorder, Major; Suicide, Attempted; Randomized Controlled Trials as Topic
PubMed: 36260324
DOI: 10.1001/jamapsychiatry.2022.3352 -
British Journal of Clinical Pharmacology Oct 2022There is a growing interest in the psychiatric properties of the dissociative anaesthetic ketamine, as single doses have been shown to have fast-acting mood-enhancing... (Review)
Review
There is a growing interest in the psychiatric properties of the dissociative anaesthetic ketamine, as single doses have been shown to have fast-acting mood-enhancing and anxiolytic effects, which persist for up to a week after the main psychoactive symptoms have diminished. Therefore, ketamine poses potential beneficial effects in patients with refractory anxiety disorders, where other conventional anxiolytics have been ineffective. Ketamine is a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor, which underlies its induction of pain relief and anaesthesia. However, the role of NMDA receptors in anxiety reduction is still relatively unknown. To fill this paucity in the literature, this systematic review assesses the evidence that ketamine significantly reduces refractory anxiety and discusses to what extent this may be mediated by NMDA receptor antagonism and other receptors. We highlight the temporary nature of the anxiolytic effects and discuss the high discrepancy among the study designs regarding many fundamental factors such as administration routes, complementary treatments and other treatments.
Topics: Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Humans; Ketamine; Receptors, N-Methyl-D-Aspartate
PubMed: 35510346
DOI: 10.1111/bcp.15374 -
Neurotoxicology Sep 2019Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the most represented phytocannabinoids in Cannabis sativa plants. However, CBD may present with a different... (Review)
Review
Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the most represented phytocannabinoids in Cannabis sativa plants. However, CBD may present with a different activity compared with the psychotomimetic THC. Most typically, CBD is reported to be used in some medical conditions, including chronic pain. Conversely, the main aim of this systematic review is to assess and summarise the available body of evidence relating to both efficacy and safety of CBD as a treatment for psychiatric disorders, alone and/or in combination with other treatments. Eligible studies included randomized controlled trials (RCT) assessing the effect of CBD in a range of psychopathological conditions, such as substance use; psychosis, anxiety, mood disturbances, and other psychiatric (e.g., cognitive impairment; sleep; personality; eating; obsessive-compulsive; post-traumatic stress/PTSD; dissociative; and somatic) disorders. For data gathering purposes, the PRISMA guidelines were followed. The initial search strategy identified some n = 1301 papers; n = 190 studies were included after the abstract's screening and n = 27 articles met the inclusion criteria. There is currently limited evidence regarding the safety and efficacy of CBD for the treatment of psychiatric disorders. However, available trials reported potential therapeutic effects for specific psychopathological conditions, such as substance use disorders, chronic psychosis, and anxiety. Further large-scale RCTs are required to better evaluate the efficacy of CBD in both acute and chronic illnesses, special categories, as well as to exclude any possible abuse liability.
Topics: Anxiety; Cannabidiol; Humans; Mental Disorders; Randomized Controlled Trials as Topic
PubMed: 31412258
DOI: 10.1016/j.neuro.2019.08.002 -
Psychiatry and Clinical... Sep 2022Reduced memory specificity (i.e., overgeneral memory) is a characteristic of autobiographical memories widely studied in clinical populations, and it is explained by... (Review)
Review
BACKGROUND
Reduced memory specificity (i.e., overgeneral memory) is a characteristic of autobiographical memories widely studied in clinical populations, and it is explained by rumination, functional avoidance, and executive dysfunction. Though the relationship of autobiographical memory specificity with mood and anxiety disorders has been shown, how it relates to dissociation is not well-established. Thus, we aimed to investigate whether dissociative experiences are related to overgeneral memory while considering concurrent depression as a possible confounding factor.
METHODS
We conducted a systematic review in compliance with The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and searched PubMed and Web of Science databases using autobiograph* and dissoc* as our keywords.
RESULTS
Of the 768 studies identified, 9 studies fulfilled the inclusion criteria. A meta-regression analysis was conducted to analyze the relationship between dissociative experiences and depression scores with autobiographical memory test scores. Our research revealed that depression scores, but not dissociative experiences, are significantly related to reduced memory specificity.
CONCLUSION
While the possible overlap between dissociation and depression should be considered in the interpretation of the findings, dissociative experiences do not seem to pose vulnerability for reduced specificity of autobiographical memory. The number of studies on the topic is limited, and they do not have longitudinal follow-ups. The heterogeneous reporting of memory scores and low scores of dissociative experiences in the samples are also limitations of the existing studies.
PubMed: 38766667
DOI: 10.5152/pcp.2022.21285 -
The American Journal of Drug and... Mar 2023Although the misuse of ketamine constitutes a worldwide issue, ketamine is quickly taking its place as a therapeutic option in the management of several mental...
Although the misuse of ketamine constitutes a worldwide issue, ketamine is quickly taking its place as a therapeutic option in the management of several mental disorders. However, the use of ketamine and/or its analogues, as well as combinations with other drugs, can be fatal. To outline the cases of overdoses and deaths related to the use of ketamine and/or its analogues, as reported in the scientific literature. To investigate if ketamine is safe in a therapeutic context, particularly in its use as an antidepressant. Electronic searches were performed on three medical databases. Articles describing cases of overdose and/or death associated with ketamine and/or its analogues were included. After the removal of duplicates, title analysis and full-text analysis, 34 articles were included in this review. Eighteen articles described fatal cases and sixteen described overdoses. Poly-substance use was mentioned in 53% of the selected articles. Most cases were males and the ages varied from two to 65 years old. A total of 312 overdose cases and 138 deaths were reported. In both death reports and overdose cases, ketamine was preponderant: 89.1% and 79%, respectively. No cases of overdose or death related to the use of ketamine as an antidepressant in a therapeutic setting were found; most of the deaths occurred in the circumstances of polydrug use and overdoses left no sequelae. There is legitimate concern about the risks involving the use of ketamine and its analogues, especially in recreational settings. On the other hand, ketamine as medicine is considered safe and it is listed as an essential medicine by the World Health Organization. Although clinicians must remain vigilant, this should not deter appropriate prescription.
Topics: Male; Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Female; Ketamine; Drug Overdose; Substance-Related Disorders; Analgesics, Opioid
PubMed: 36410032
DOI: 10.1080/00952990.2022.2132506 -
Journal of Affective Disorders Jun 2023ECT is considered the fastest and most effective treatment for TRD. Ketamine seems to be an attractive alternative due to its rapid-onset antidepressant effects and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
ECT is considered the fastest and most effective treatment for TRD. Ketamine seems to be an attractive alternative due to its rapid-onset antidepressant effects and impact on suicidal thoughts. This study aimed to compare efficacy and tolerability of ECT and ketamine for different depression outcomes (PROSPERO/CRD42022349220).
METHODS
We searched MEDLINE, Web of Science, Embase, PsycINFO, Google Scholar, Cochrane Library and trial registries, which were the ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform, without restrictions on publication date.
SELECTION CRITERIA
randomized controlled trials or cohorts comparing ketamine versus ECT in patients with TRD.
RESULTS
Eight studies met the inclusion criteria (of 2875 retrieved). Random-effects models comparing ketamine and ECT regarding the following outcomes were conducted: a) reduction of depressive symptoms severity through scales, g = -0.12, p = 0.68; b) response to therapy, RR = 0.89, p = 0.51; c) reported side-effects: dissociative symptoms, RR = 5.41, p = 0.06; nausea, RR = 0.73, p = 0.47; muscle pain, RR = 0.25, p = 0.02; and headache, RR = 0.39, p = 0.08. Influential & subgroup analyses were performed.
LIMITATIONS
Methodological issues with high risk of bias in some of the source material, reduced number of eligible studies with high in-between heterogeneity and small sample sizes.
CONCLUSION
Our study showed no evidence to support the superiority of ketamine over ECT for severity of depressive symptoms and response to therapy. Regarding side effects, there was a statistically significant decreased risk of muscle pain in patients treated with ketamine compared to ECT.
Topics: Humans; Ketamine; Depressive Disorder, Major; Electroconvulsive Therapy; Myalgia; Antidepressive Agents
PubMed: 36907464
DOI: 10.1016/j.jad.2023.02.152 -
Psychology of Addictive Behaviors :... May 2021Multilevel consequences related to gambling disorder (GD) are glaring enough to make gambling a worldwide public health issue. Dissociation has been pointed out in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Multilevel consequences related to gambling disorder (GD) are glaring enough to make gambling a worldwide public health issue. Dissociation has been pointed out in clinical, empirical, and theoretical contributions as a key variable accounting for the development and maintenance of GD. However, we still lack a systematization of available empirical data that may facilitate further accurate conclusions.
METHOD
A systematic review and meta-analysis were performed with the goal to answer to open questions. We followed the PRISMA guidelines conducting a systematic search of 5 scientific databases (PsycINFO, PsycARTICLES, MEDLINE, Scopus, Web of Science, and PubMed) including grey literature.
RESULTS
A total of 843 records were screened, and 20 studies were included in the qualitative and quantitative analyses. A systematic review of selected studies outlines the high heterogeneity in the operationalization of the dissociation construct as well as the absence of studies examining the role played by the specific dimensions of the pathological dissociative feature in GD. A significant, positive, and moderate effect size (r = .37) was found linking GD to dissociation. Moreover, this effect appears to not be moderated by the quality of studies, age, and gender of participants nor measures used to evaluate dissociation.
CONCLUSIONS
Despite empirical evidences supporting the theoretical assertions toward the relationship between GD and dissociation, few studies have reached an articulated understanding of this topic, mostly failing to identify specific dissociative features involved in GD. Furthermore, the existence of the current gap in the literature are discussed to delineate future lines of research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Topics: Dissociative Disorders; Gambling; Humans
PubMed: 33646797
DOI: 10.1037/adb0000693 -
European Journal of Paediatric... Jan 2018Dissociative disorders present a huge challenge in clinical settings. In contrast to other dissociative symptoms, dissociative sensibility disorders are rarely focused... (Review)
Review
CONTEXT
Dissociative disorders present a huge challenge in clinical settings. In contrast to other dissociative symptoms, dissociative sensibility disorders are rarely focused on.
OBJECTIVE
To identify the clinical characteristics and outcomes of dissociative sensibility disorders in children and adolescents, and to review the use of diagnostic procedures.
DATA SOURCES
For the review, a literature search used Pubmed, Embase, Web of Science, and PubPsych (to 02/2015) and the reference lists of the studies identified.
STUDY SELECTION
Screening of titles and abstracts; full-text assessment by two reviewers.
DATA SELECTION
The original case series was identified by using the local data register.
DATA EXTRACTION
Two reviewers independently reviewed the data and, if they agreed on the relevance, extracted the data. In the original case series, data were extracted retrospectively from the records.
RESULTS
Sixteen studies and seven case reports were identified, including 931 cases with dissociative disorders. In 210 cases the patient suffered either from a single sensibility disorder or predominantly from sensibility disorders. We identified thirteen further cases in our cohort. In both groups there was female predominance; the mean age of manifestation was early adolescence. The timing of admissions was variable. In approximately 50% of cases a premorbid stressful life event could be identified. Over 75% of cases had a good prognosis with complete resolution.
LIMITATIONS
Retrospective character of our own data collection, partially missing differentiation between the subgroups of dissociative disorders in the reviewed studies.
CONCLUSIONS
There is no uniform procedure for diagnostic work-up. The overall short-term prognosis is good.
Topics: Adolescent; Child; Dissociative Disorders; Female; Humans; Male; Prognosis; Retrospective Studies
PubMed: 28899586
DOI: 10.1016/j.ejpn.2017.08.005 -
European Journal of Psychotraumatology 2023The clinical guidelines for the treatment of dissociation focus primarily on psychotherapy. However, different psychoactive drugs are used in clinical practice. The use... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The clinical guidelines for the treatment of dissociation focus primarily on psychotherapy. However, different psychoactive drugs are used in clinical practice. The use of opioid antagonists has been proposed as a therapeutic option based on the theory that dissociation might be a phenomenon mediated by dysregulation of the endogenous opioid system.
OBJECTIVE
To review and meta-analyse the available evidence on the efficacy of the opioid antagonists naltrexone, naloxone, and nalmefene as treatments for dissociative symptoms and disorders.
METHOD
The PRISMA guidelines were followed, and this review was registered in Prospero with reference number CRD42021280976. The search was performed in the PubMed, Scopus, Web of Science, EMBASE, PsycINFO, and PubPsych databases.
RESULTS
1,798 citations were obtained. After removing duplicates and applying inclusion and exclusion criteria, we included 5 comparative studies with 9 dissociation measures that had included a total of 154 participants, of whom 134 had been treated with an opioid antagonist. The results of the meta-analysis showed a treatment effect for dissociation when using opioid antagonists [pooled = 1.46 (95% CI: 0.62-2.31)]. However, the studies we included were very heterogeneous [Q = 66.89 ( < .001)] and there may have been publication bias.
CONCLUSIONS
Although more research is needed and the results must be interpreted with caution because of the limited amount of data and heterogeneity in the studies and their methodological qualities, opioid antagonists (particularly naltrexone) are promising candidates for the treatment of dissociative symptoms and showed a moderate - large effect size in reducing these symptoms.
Topics: Humans; Narcotic Antagonists; Naltrexone; Naloxone; Dissociative Disorders
PubMed: 37860852
DOI: 10.1080/20008066.2023.2265184 -
Therapeutic Advances in... 2023More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage... (Review)
Review
BACKGROUND
More than 2% of the general population experience suicidal ideas each year and a large number of them will attempt suicide. Evidence-based therapeutic options to manage suicidal crisis are currently limited.
OBJECTIVES
The aim of this study was to overview the findings on the use of ketamine and esketamine for the treatment of suicidal ideas and acts.
DESIGN
Systematic review.
DATA SOURCES AND METHODS
PubMed, article references, and Clinicaltrials.gov up to June 30, 2022. Meta-analyses published within the last 2 years were also reviewed.
RESULTS
We identified 12 randomized controlled trials with reduction of suicidal ideation as the primary objective and 14 trials as secondary objectives. Intravenous racemic ketamine was superior to control drugs (placebo or midazolam) within the first 72 h, in spite of large placebo effects. Adverse events were minor and transient. In contrast, intranasal esketamine did not differ from placebo in large-scale studies. Limitations, clinical considerations, and opportunities for future research include the following points: large placebo effects when studying suicidal ideation reduction; small concerns about blinding quality due to dissociative effects; no studies on the risk/prevention of suicidal acts and mortality; lack of studies beyond affective disorders; no studies in adolescents and older people; lack of knowledge of long-term side effects, notably liability for abuse; no robust predictive markers; limited understanding of the mechanisms of ketamine on suicidal ideas; need for improved assessment of suicidal ideation in clinical trials; need for studies in outpatient settings, emergency room, and liaison consultation; need for research on ketamine administration; limited knowledge on the positive and negative effects of concomitant treatments.
CONCLUSION
Overall, there is compelling evidence for a favorable short-term benefit-risk balance with intravenous racemic ketamine but not intranasal esketamine. The place of ketamine will have to be defined within a multimodal care strategy for suicidal patients. Caution remains necessary for clinical use, and pharmacovigilance will be essential.
PubMed: 36776623
DOI: 10.1177/20451253231151327