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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 -
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 -
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 -
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 -
Journal of Personalized Medicine Aug 2022Dissociative disorders encompass loss of integration in essential functions such as memory, consciousness, perception, motor control, and identity. Nevertheless,... (Review)
Review
BACKGROUND
Dissociative disorders encompass loss of integration in essential functions such as memory, consciousness, perception, motor control, and identity. Nevertheless, neuroimaging studies, albeit scarce, have suggested the existence of particular brain activation patterns in patients belonging to this diagnostic category. The aim of this review is to identify the main functional neuroimaging correlates of dissociative disorders.
METHODS
we searched the PubMed database to identify functional neuroimaging studies conducted on subjects with a diagnosis of a dissociative disorder, following the PRISMA guidelines. In the end, we included 13 studies in this systematic review, conducted on 51 patients with dissociative identity disorder (DID), 28 subjects affected by depersonalization disorder, 24 with dissociative amnesia, and 6 with other or not specified dissociative disorders.
RESULTS
Prefrontal cortex dysfunction seems prominent. In addition, changes in the functional neural network of the caudate are related to alterations of identity state and maintenance of an altered mental status in DID. Another role in DID seems to be played by a dysfunction of the anterior cingulate gyrus. Other regions, including parietal, temporal, and insular cortices, and subcortical areas were reported to be dysfunctional in dissociative disorders.
CONCLUSIONS
Prefrontal dysfunction is frequently reported in dissociative disorders. Functional changes in other cortical and subcortical areas can be correlated with these diagnoses. Further studies are needed to clarify the neurofunctional correlations of each dissociative disorder in affected patients, in order to identify better tailored treatments.
PubMed: 36143190
DOI: 10.3390/jpm12091405 -
Cells Feb 2022Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been... (Review)
Review
BACKGROUND AND OBJECTIVES
Ketamine is a rapid-acting antidepressant with proven efficacy as an add-on agent in unipolar and bipolar treatment-resistant depression. Although many studies have been published, there is still not enough data on the effect of ketamine in combination with other medications. Particularly interesting is the combination of ketamine and lamotrigine, and its potential role in bipolar depression. The aim of this review was to identify animal and human studies in which ketamine and lamotrigine were used together in order to find out if there is scientific ground for combining ketamine and lamotrigine in the treatment of mood disorders. Directions for future studies are presented.
MATERIALS AND METHODS
PubMed and Web of Science were searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA 2020 methodology was applied.
RESULTS
Seventeen studies were included for review. Animal studies using models of depression suggested a synergistic effect of ketamine and lamotrigine in combination. Studies on healthy humans showed a reduction in ketamine-induced dissociative symptoms with lamotrigine pretreatment. In a study on patients with depression, ketamine and lamotrigine did not have a stronger antidepressant effect than ketamine alone, but in this study only one ketamine infusion was administered. One case series described the antidepressant and anti-suicidal effect of the combination in two bipolar patients. Available clinical studies on patients with mood disorders did not support the hypothesis that lamotrigine reduces ketamine-induced dissociative symptoms.
CONCLUSIONS
The results of the analyzed studies were not sufficient to answer any of the stated questions; however, they allowed us to delineate future research directions. The identified animal studies suggested a possible synergistic antidepressant effect of ketamine and lamotrigine. The available clinical studies were not conclusive. No controlled studies on large groups of bipolar patients with multiple ketamine infusions combined with lamotrigine treatment have been published so far. There is some evidence for the reduction of ketamine's side effects by lamotrigine, and there are reports suggesting that lamotrigine can reduce ketamine craving. More studies with follow-up are needed in order to investigate the ketamine-lamotrigine combination in bipolar patients.
Topics: Animals; Antidepressive Agents; Depression; Humans; Ketamine; Lamotrigine; Psychopharmacology
PubMed: 35203296
DOI: 10.3390/cells11040645 -
BJPsych Open Dec 2022Studies have reported elevated rates of dissociative symptoms and comorbid dissociative disorders in functional neurological disorder (FND); however, a comprehensive... (Review)
Review
BACKGROUND
Studies have reported elevated rates of dissociative symptoms and comorbid dissociative disorders in functional neurological disorder (FND); however, a comprehensive review is lacking.
AIMS
To systematically review the severity of dissociative symptoms and prevalence of comorbid dissociative disorders in FND and summarise their biological and clinical associations.
METHOD
We searched Embase, PsycInfo and MEDLINE up to June 2021, combining terms for FND and dissociation. Studies were eligible if reporting dissociative symptom scores or rates of comorbid dissociative disorder in FND samples. Risk of bias was appraised using modified Newcastle-Ottawa criteria. The findings were synthesised qualitatively and dissociative symptom scores were included in a meta-analysis (PROSPERO CRD42020173263).
RESULTS
Seventy-five studies were eligible (FND = 3940; control = 3073), most commonly prospective case-control studies ( = 54). Dissociative disorders were frequently comorbid in FND. Psychoform dissociation was elevated in FND compared with healthy ( = 0.90, 95% CI 0.66-1.14, = 70%) and neurological controls ( = 0.56, 95% CI 0.19-0.92, = 67%). Greater psychoform dissociation was observed in FND samples with seizure symptoms versus healthy controls ( = 0.94, 95% CI 0.65-1.22, = 42%) and FND samples with motor symptoms ( = 0.40, 95% CI -0.18 to 1.00, = 54%). Somatoform dissociation was elevated in FND versus healthy controls ( = 1.80, 95% CI 1.25-2.34, = 75%). Dissociation in FND was associated with more severe functional symptoms, worse quality of life and brain alterations.
CONCLUSIONS
Our findings highlight the potential clinical utility of assessing patients with FND for dissociative symptomatology. However, fewer studies investigated FND samples with motor symptoms and heterogeneity between studies and risk of bias were high. Rigorous investigation of the prevalence, features and mechanistic relevance of dissociation in FND is needed.
PubMed: 36451595
DOI: 10.1192/bjo.2022.597 -
World Journal of Psychiatry Oct 2019Dissociation, which is defined as the failure to associate consciousness, memory, identity, emotion, perception, body representation, motor control, and behavior into an...
BACKGROUND
Dissociation, which is defined as the failure to associate consciousness, memory, identity, emotion, perception, body representation, motor control, and behavior into an integrated whole, has long been assumed to be generated by trauma. If dissociation is a product of trauma exposure, then dissociation would be a major mental health outcome observed in studies of disaster survivors. Although some studies have examined dissociation in disasters, no systematic literature reviews have been conducted to date on the topic.
AIM
To systematically evaluate the literature on the association between disaster and dissociation to determine the prevalence and incidence of dissociation after exposure to disaster and further examine their relationship.
METHODS
EMBASE, Medline, and PsychINFO were searched from inception to January 1, 2019 to identify studies examining dissociative disorders or symptoms related to a disaster in adult or child disaster survivors and disaster responders. Studies of military conflicts and war, articles not in English, and those with samples of 30 or more participants were excluded. Search terms used were "disaster*" and dissociation ("dissociat*," "multiple personality," "fugue," "psychogenic amnesia," "derealization," and "depersonalization"). Reference lists of identified articles were scrutinized to identify studies for additional articles.
RESULTS
The final number of articles in the review was 53, including 36 articles with samples of adults aged 18 and above, 5 of children/adolescents under age 18, and 12 of disaster workers. Included articles studied several types of disasters that occurred between 1989 and 2017, more than one-third (38%) from the United States. Only two studies had a primary aim to investigate dissociation in relation to disaster and none reported data on dissociative disorders. All of the studies used self-report symptom scales; none used structured interviews providing full diagnostic assessment of dissociative disorders or other psychopathology. Several studies mixed exposed and unexposed samples or did not differentiate outcomes between exposure groups. Studies examining associations between dissociation and disaster exposure have been inconclusive. The majority (75%) of the studies compared dissociation with posttraumatic stress, with inconsistent findings. Dissociation was found to be associated with a wide range of other psychiatric disorders, symptoms, and negative emotional, cognitive, and functional states.
CONCLUSION
The studies reviewed had serious methodological limitations including problems with measurement of psychopathology, sampling, and generation of unwarranted conclusions, precluding conclusions that dissociation is an established outcome of disaster.
PubMed: 31649861
DOI: 10.5498/wjp.v9.i6.83