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Biological Psychiatry Feb 2022
Topics: Dissociative Disorders; Dissociative Identity Disorder; Humans; Interview, Psychological; Neurosciences; Psychiatric Status Rating Scales
PubMed: 34961597
DOI: 10.1016/j.biopsych.2021.11.004 -
Annales Pharmaceutiques Francaises Jan 2022The history of ketamine begins in 1962, when Calvin Stevens of the pharmaceutical laboratory Parke-Davis synthesizes it from phencyclidine, a molecule with... (Review)
Review
The history of ketamine begins in 1962, when Calvin Stevens of the pharmaceutical laboratory Parke-Davis synthesizes it from phencyclidine, a molecule with psychodysleptic, hallucinogenic and dissociative properties. Following the first administration of ketamine to humans in 1964 in Jackson prison (Michigan, USA), its dissociative effects associated with short anaesthesia were reported, and a patent for its human use was filed in 1966. In the 1990s, the discovery of opioid-induced hyperalgesia sparked interest in ketamine as an analgesic. In recent years, the human use of ketamine, and in particular its esketamine enantiomer, has shifted towards the treatment of depression. The first cases of ketamine abuse were reported in 1992 in France, leading to special surveillance by the health authorities, and its inclusion in the list of narcotic drugs in 1997. Today, ketamine has become an attractive substance for recreational use, gradually emerging from alternative techno circles to spread to more commercial party scenes. These elements represent a public health concern, associated with the risk of developing new chemically synthesized analogues, the harmful effects of which are still little known.
Topics: Anesthetics, Dissociative; History, 20th Century; History, 21st Century; Humans; Ketamine; Stereoisomerism; Substance-Related Disorders
PubMed: 33915159
DOI: 10.1016/j.pharma.2021.04.005 -
Nature Oct 2020Advanced imaging methods now allow cell-type-specific recording of neural activity across the mammalian brain, potentially enabling the exploration of how brain-wide...
Advanced imaging methods now allow cell-type-specific recording of neural activity across the mammalian brain, potentially enabling the exploration of how brain-wide dynamical patterns give rise to complex behavioural states. Dissociation is an altered behavioural state in which the integrity of experience is disrupted, resulting in reproducible cognitive phenomena including the dissociation of stimulus detection from stimulus-related affective responses. Dissociation can occur as a result of trauma, epilepsy or dissociative drug use, but despite its substantial basic and clinical importance, the underlying neurophysiology of this state is unknown. Here we establish such a dissociation-like state in mice, induced by precisely-dosed administration of ketamine or phencyclidine. Large-scale imaging of neural activity revealed that these dissociative agents elicited a 1-3-Hz rhythm in layer 5 neurons of the retrosplenial cortex. Electrophysiological recording with four simultaneously deployed high-density probes revealed rhythmic coupling of the retrosplenial cortex with anatomically connected components of thalamus circuitry, but uncoupling from most other brain regions was observed-including a notable inverse correlation with frontally projecting thalamic nuclei. In testing for causal significance, we found that rhythmic optogenetic activation of retrosplenial cortex layer 5 neurons recapitulated dissociation-like behavioural effects. Local retrosplenial hyperpolarization-activated cyclic-nucleotide-gated potassium channel 1 (HCN1) pacemakers were required for systemic ketamine to induce this rhythm and to elicit dissociation-like behavioural effects. In a patient with focal epilepsy, simultaneous intracranial stereoencephalography recordings from across the brain revealed a similarly localized rhythm in the homologous deep posteromedial cortex that was temporally correlated with pre-seizure self-reported dissociation, and local brief electrical stimulation of this region elicited dissociative experiences. These results identify the molecular, cellular and physiological properties of a conserved deep posteromedial cortical rhythm that underlies states of dissociation.
Topics: Action Potentials; Animals; Behavior; Brain Waves; Cerebral Cortex; Dissociative Disorders; Electrophysiology; Female; Humans; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Ketamine; Male; Mice; Mice, Inbred C57BL; Neurons; Optogenetics; Self Report; Thalamus
PubMed: 32939091
DOI: 10.1038/s41586-020-2731-9 -
European Journal of Psychotraumatology 2021About 40% of rape victims develop post-traumatic stress disorder (PTSD) within three months after the assault. Considering the high personal and societal impact of PTSD,... (Randomized Controlled Trial)
Randomized Controlled Trial
Early intervention with eye movement desensitization and reprocessing (EMDR) therapy to reduce the severity of post-traumatic stress symptoms in recent rape victims: a randomized controlled trial.
BACKGROUND
About 40% of rape victims develop post-traumatic stress disorder (PTSD) within three months after the assault. Considering the high personal and societal impact of PTSD, there is an urgent need for early (i.e. within three months after the incident) interventions to reduce post-traumatic stress in victims of rape.
OBJECTIVE
To assess the effectiveness of early intervention with eye movement desensitization and reprocessing (EMDR) therapy to reduce symptoms of post-traumatic stress, feelings of guilt and shame, sexual dysfunction, and other psychological dysfunction (i.e. general psychopathology, anxiety, depression, and dissociative symptoms) in victims of rape.
METHOD
This randomized controlled trial included 57 victims of rape, who were randomly allocated to either two sessions of EMDR therapy or treatment as usual ('watchful waiting') between 14 and 28 days post-rape. Psychological symptoms were assessed at pre-treatment, post-treatment, and 8 and 12 weeks post-rape. Linear mixed models and ANCOVAs were used to analyse differences between conditions over time.
RESULTS
Within-group effect sizes of the EMDR condition ( = 0.89 to 1.57) and control condition ( = 0.79 to 1.54) were large, indicating that both conditions were effective. However, EMDR therapy was not found to be more effective than watchful waiting in reducing post-traumatic stress symptoms, general psychopathology, depression, sexual dysfunction, and feelings of guilt and shame. Although EMDR therapy was found to be more effective than watchful waiting in reducing anxiety and dissociative symptoms in the post-treatment assessment, this effect disappeared over time.
CONCLUSIONS
The findings do not support the notion that early intervention with EMDR therapy in victims of rape is more effective than watchful waiting for the reduction of psychological symptoms, including symptoms of post-traumatic stress. Further research on the effectiveness of early interventions, including watchful waiting, for this specific target group is needed.
Topics: Adult; Anxiety; Crime Victims; Depression; Eye Movement Desensitization Reprocessing; Female; Humans; Netherlands; Rape; Stress Disorders, Post-Traumatic; Watchful Waiting
PubMed: 34531963
DOI: 10.1080/20008198.2021.1943188 -
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 -
Journal of Behavior Therapy and... Sep 2021We described a new treatment model for Posttraumatic Stress Disorder (PTSD) and Dissociative Identity Disorder (DID), based on cognitive-behavioural principles. In this...
BACKGROUND AND OBJECTIVES
We described a new treatment model for Posttraumatic Stress Disorder (PTSD) and Dissociative Identity Disorder (DID), based on cognitive-behavioural principles. In this model, dissociation is seen as a maladaptive avoidant coping strategy. In addition, we stress that patients have dysfunctional beliefs about dissociation. Both elements, avoidance behaviour and dysfunctional beliefs, are challenged during the brief, intensive trauma-focused treatment. When the PTSD-symptoms decrease, the patient is offered a fare-well ritual to say goodbye to their identities in one or more additional sessions.
METHODS
We illustrate this treatment approach with a case report of a woman with PTSD as a result of sexual abuse in her childhood, and DID with four identities. Treatment outcome was measured at intake, at pre-treatment, at post-treatment and at 3 and 6 months follow-up.
RESULTS
After the short treatment of only 2 weeks, she no longer fulfilled the DSM-5 diagnostic criteria for PTSD nor DID. These results were maintained at the follow-ups.
LIMITATIONS
Although we included a baseline-controlled time phase, it was not a controlled study, and only one patient was treated.
CONCLUSIONS
This new treatment model for DID-patients is promising but results should be interpreted cautiously since we described only one patient.
Topics: Child; Cognition; Cognitive Behavioral Therapy; Dissociative Disorders; Dissociative Identity Disorder; Female; Humans; Stress Disorders, Post-Traumatic
PubMed: 33848810
DOI: 10.1016/j.jbtep.2021.101655 -
Borderline Personality Disorder and... Apr 2022Dissociation is a complex phenomenon, which occurs in various clinical conditions, including dissociative disorders, (complex) post-traumatic stress disorder (CPTSD,...
Dissociation is a complex phenomenon, which occurs in various clinical conditions, including dissociative disorders, (complex) post-traumatic stress disorder (CPTSD, PTSD), and borderline personality disorder (BPD). Traumatic stress is considered an important risk factor, while the etiology of dissociation is still debated. Next to traumatic experiences, temperamental and neurobiological vulnerabilities seem to contribute to the development of dissociation. Stress-related dissociation is a prevalent symptom of BPD, which may interfere with psychosocial functioning and treatment outcome. More research in the field is strongly needed to improve the understanding and management of this complex phenomenon. This article collection brings together research on dissociation and trauma, with a special focus on BPD or sub-clinical expressions of BPD. In this editorial, recent conceptualizations of dissociation and relevant previous research are introduced in order to provide a framework for this novel research.
PubMed: 35440020
DOI: 10.1186/s40479-022-00184-y -
Neuropsychopharmacology : Official... Jun 2023This study is the first randomized controlled trial to test the effects of ketamine in Borderline Personality Disorder (BPD). BPD remains undertreated in the community... (Randomized Controlled Trial)
Randomized Controlled Trial
This study is the first randomized controlled trial to test the effects of ketamine in Borderline Personality Disorder (BPD). BPD remains undertreated in the community and no medication has FDA approval for this indication. People with BPD experience chronic mood disturbances with depressed mood, suicidal ideation, and severe social difficulties. In this double-blind, randomized controlled pilot study, we tested the effects of one infusion of ketamine (0.5 mg/kg, n = 10) or the psychoactive comparator drug midazolam (0.04 mg/kg, n = 12) in adults with BPD. Infusions were well tolerated in both groups. Dissociative symptoms during infusion were more intense with ketamine than midazolam (t(12.3) = 3.61, p = 0.01), but they resolved by 40 min after infusion in both groups. Post-infusion adverse events were at the expected low levels in both groups. For our primary outcome measure of suicidal ideation and our secondary outcome measure of depression, we found numerical reduction but not significant group or group x timepoint difference (p > 0.05). For our secondary outcome measures of anxiety and BPD symptoms, we did not observe group or group x timepoint differences. There was a group x timepoint effect for socio-occupational functioning (F(1,20.12) = 5.16, p = 0.03, at Day 14, ketamine group showed more improvement than midazolam group). An exploratory analysis revealed that improvement in socio-occupational functioning was correlated with improvement in depression in the ketamine group (r(8) = 0.65, p = 0.04) but not midazolam group (r(9) = 0.41, p = 0.216). This pilot study provides the first randomized controlled evidence of the effects of antidepressant-dosed ketamine in people with BPD. Our results provide reason for optimism that antidepressant-dosed ketamine will be well-tolerated in larger studies and may provide clinical benefit for mood symptoms and related impairments in people with BPD.
Topics: Adult; Humans; Ketamine; Pilot Projects; Borderline Personality Disorder; Midazolam; Antidepressive Agents; Double-Blind Method
PubMed: 36804489
DOI: 10.1038/s41386-023-01540-4 -
Ugeskrift For Laeger Nov 2022This case report describes a 16-year-old patient, who presented with multiple personalities. A diagnosis of dissociative identity disorder (DID) was considered, but...
This case report describes a 16-year-old patient, who presented with multiple personalities. A diagnosis of dissociative identity disorder (DID) was considered, but rejected, based on the patient's presenting psychopathology and a lack of confidence in the current scientific literature describing the diagnosis. DID is a rare diagnosis in Danish clinical practice and there is much dissent concerning its validity.
Topics: Female; Humans; Adolescent; Dissociative Identity Disorder
PubMed: 36426835
DOI: No ID Found