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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 -
Canadian Journal of Psychiatry. Revue... Feb 2021Patients with major depressive disorder often have limited response to first-line and second-line medications; hence, novel pharmacological treatments are needed for...
The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L'humeur Et De L'anxiété (Canmat) Concernant...
OBJECTIVE
Patients with major depressive disorder often have limited response to first-line and second-line medications; hence, novel pharmacological treatments are needed for treatment-resistant depression (TRD). Ketamine, an -methyl-d-aspartate (NMDA) receptor antagonist, has demonstrated rapid antidepressant effects in patients with TRD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence for efficacy and safety of racemic ketamine and to provide recommendations for its use in clinical practice.
METHODS
A systematic review was conducted with computerized search of electronic databases up to January 31, 2020 using combinations of search terms, inspection of bibliographies, and review of other ketamine guidelines and consensus statements. The level of evidence and lines of treatment were assigned according to CANMAT criteria. Recommendations were given in question-answer format.
RESULTS
Intravenous (IV) racemic ketamine given as a single infusion has Level 1 evidence for efficacy in adults with TRD. The evidence for multiple infusions, given as an acute series or as ongoing maintenance treatment, is limited to Level 3. Adverse events associated with ketamine infusions include behavioral (e.g., dissociative symptoms) and physiological (e.g., hypertension) events. There is only Level 3 or 4 evidence for non-IV formulations of racemic ketamine. Consensus recommendations are given for clinical administration of IV ketamine including patient selection, facility and personnel issues, monitoring, and maintaining response.
CONCLUSIONS
Single-dose IV racemic ketamine is a third-line recommendation for adults with TRD. The need for repeated and maintenance ketamine infusions should be carefully assessed on a case-by-case basis with consideration of potential risks and benefits. Because of limited evidence for efficacy and risk for misuse and diversion, the use of oral and other formulations of racemic ketamine should be limited to specialists with ketamine-prescribing expertise and affiliations with tertiary or specialized centers.
Topics: Adult; Antidepressive Agents; Anxiety; Canada; Depressive Disorder, Major; Humans; Ketamine
PubMed: 33174760
DOI: 10.1177/0706743720970860 -
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 -
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 -
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 -
The Australian and New Zealand Journal... Oct 2022Borderline Personality Disorder (BPD) is frequently complicated by the presence of dissociative symptoms. Pathological dissociation is linked with earlier and more... (Review)
Review
BACKGROUND
Borderline Personality Disorder (BPD) is frequently complicated by the presence of dissociative symptoms. Pathological dissociation is linked with earlier and more severe trauma exposure, emotional dysregulation and worse treatment outcomes in Posttraumatic Stress Disorder and Dissociative Disorders, with implications for BPD.
OBJECTIVE
A systematic scoping review was conducted to assess the extent of current literature regarding the impact of dissociation on BPD and to identify knowledge gaps.
METHODS
Four electronic databases (MEDLINE, APA PsycINFO, EMBASE, CINAHL Plus) were searched, and English peer-reviewed studies with adults with BPD were included, following Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) extension for scoping reviews (PRISMA-ScR) 2018 guidelines.
RESULTS
Most of the 70 included studies were observational (98%) with first authors from Germany (59%). Overall, dissociation was associated with increased BPD symptom severity, self-harm and reduced psychotherapy treatment response; findings regarding suicide risk were mixed. Dissociation was associated with working memory and cognitive deficits, decreased pain perception, altered body ownership, no substance abuse or the abuse of sedative substances, increased fantasy proneness, personality fragmentation, fearful attachment, dream anxiety, perceived stress and altered stress responses, increased cumulative body mass index, decreased water consumption, several neurological correlates and changes in gene expression.
CONCLUSION
BPD with significant dissociative symptoms may constitute a more severe and at-risk subgroup of BPD patients. However, there are significant research gaps and methodological issues in the area, including the possibility of unrecognized Dissociative Disorders in BPD study populations confounding results. Further studies are needed to better understand the impact of dissociation on BPD course and treatment, and to clarify the most appropriate assessment tools for clinical practice. In addition, interventional studies are needed to develop dissociation-specific BPD treatments to determine whether targeting dissociation in BPD can improve treatment outcomes.
Topics: Adult; Borderline Personality Disorder; Dissociative Disorders; Humans; Hypnotics and Sedatives; Psychotherapy; Self-Injurious Behavior
PubMed: 35152771
DOI: 10.1177/00048674221077029 -
Journal of Affective Disorders Sep 2023Patients with Post-traumatic stress disorder (PTSD) exposed to traumatic reminders show hyperreactivity in brain areas (e.g., amygdala) belonging or related to the... (Meta-Analysis)
Meta-Analysis Review
Patients with Post-traumatic stress disorder (PTSD) exposed to traumatic reminders show hyperreactivity in brain areas (e.g., amygdala) belonging or related to the Innate Alarm System (IAS), allowing the rapid processing of salient stimuli. Evidence that IAS is activated by subliminal trauma-reminders could shed a new light on the factors precipitating and perpetuating PTSD symptomatology. Thus, we systematically reviewed studies investigating neuroimaging correlates of subliminal stimulation in PTSD. Twenty-three studies were selected from the MEDLINE and Scopus® databases for a qualitative synthesis, 5 of which allowed a further meta-analysis of fMRI data. The intensity of IAS responses to subliminal trauma-related reminders ranged from a minimum in healthy controls to a maximum in the PTSD patients with the most severe (e.g., dissociative) symptoms or the least responsiveness to treatment. Comparisons with other disorders (e.g., phobias) revealed contrasting results. Our findings demonstrate the hyperactivation of areas belonging or related to IAS in response to unconscious threats that should be integrated in diagnostic as well as in therapeutic protocols.
Topics: Humans; Stress Disorders, Post-Traumatic; Subliminal Stimulation; Brain; Amygdala; Brain Mapping; Magnetic Resonance Imaging
PubMed: 37236272
DOI: 10.1016/j.jad.2023.05.047 -
General Hospital Psychiatry 2024Functional neurological disorder (FND) involves the presence of neurological symptoms that cannot be explained by neurological disease. FND has long been linked to... (Review)
Review
OBJECTIVE
Functional neurological disorder (FND) involves the presence of neurological symptoms that cannot be explained by neurological disease. FND has long been linked to hypnosis and suggestion, both of which have been used as treatments. Given ongoing interest, this review examined evidence for the efficacy of hypnosis and suggestion as treatment interventions for FND.
METHOD
A systematic search of bibliographic databases was conducted to identify group studies published over the last hundred years. No restrictions were placed on study design, language, or clinical setting. Two reviewers independently assessed papers for inclusion, extracted data, and rated study quality.
RESULTS
The search identified 35 studies, including 5 randomised controlled trials, 2 non-randomised trials, and 28 pre-post studies. Of 1584 patients receiving either intervention, 1379 (87%) showed significant improvements, including many who demonstrated resolution of their symptoms in the short-term. Given the heterogeneity of interventions and limitations in study quality overall, more formal quantitative synthesis was not possible.
CONCLUSIONS
The findings highlight longstanding and ongoing interest in using hypnosis and suggestion as interventions for FND. While the findings appear promising, limitations in the evidence base, reflecting limitations in FND research more broadly, prevent definitive recommendations. Further research seems warranted given these supportive findings.
Topics: Humans; Conversion Disorder; Dissociative Disorders; Hypnosis; Nervous System Diseases
PubMed: 38154334
DOI: 10.1016/j.genhosppsych.2023.12.006 -
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