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Cureus Dec 2023Dissociative disorders have been present in our society since time immemorial, with culture, society, and spiritual beliefs playing a major part. It went through many...
Dissociative disorders have been present in our society since time immemorial, with culture, society, and spiritual beliefs playing a major part. It went through many changes from its name and what it constituted. Diagnosis can be made based on the International Classification of Diseases (ICD) 10, Diagnostic and Statistical Manual of Mental Disorders (DSM) 5, and now the current International Classification of Diseases (ICD) 11 criteria. One of its constituents is trance and possession disorder which is one of the main obstacles faced by psychiatrists in Indian society. Through this case, we can assume that there are many factors involved that lead to delays in diagnosing and managing a case of dissociative disorder, most importantly the social and cultural factors. Even now cultural-socio-spiritual beliefs add to the challenge of dissociative disorders. This case reveals that individuals first consult a general physician before visiting a psychiatrist; so, the need for consultation liaison psychiatry (CLP) and its role today in diagnosis and further management is emphasized. There still exists a need for awareness to be made regarding the mind-body relationship and psychosocial support to both patients and their relatives keeping in mind their beliefs.
PubMed: 38192943
DOI: 10.7759/cureus.50198 -
Therapeutic Advances in... 2023The therapeutic potential of subanesthetic doses of ketamine appears promising in unipolar depression; however, its effectiveness in treating bipolar depression (BD)...
BACKGROUND
The therapeutic potential of subanesthetic doses of ketamine appears promising in unipolar depression; however, its effectiveness in treating bipolar depression (BD) remains uncertain.
OBJECTIVE
This systematic review aimed to summarize findings on the use of ketamine for the treatment of BD by assessing its efficacy, safety, and tolerability.
DESIGN
Systematic review.
METHODS
We conducted a systematic review of studies that investigated the use of ketamine for adults with BD. We searched PubMed and Embase for relevant randomized-controlled trials, open-label trials, and retrospective chart analyses published from inception to 13 March 2023.
RESULTS
Eight studies were identified [pooled = 235; mean (SD) age: 45.55 (5.54)]. All participants who received intravenous (IV) ketamine were administered a dose of 0.5-0.75 mg/kg as an adjunctive treatment to a mood-stabilizing agent, whereas participants who received esketamine were administered a dosage ranging from 28 to 84 mg. Flexible dosing was used in real-world analyses. A total of 48% of participants receiving ketamine achieved a response (defined as ⩾50% reduction in baseline depression severity), whereas only 5% achieved a response with a placebo. Real-world studies demonstrated lower rates of response (30%) compared to the average across clinical trials (63%). Reductions in suicidal ideation were noted in some studies, although not all findings were statistically significant. Ketamine and esketamine were well tolerated in most participants; however, six participants (2% of the overall sample pool, 5 receiving ketamine) developed hypomanic/manic symptoms after infusions. Significant dissociative symptoms were observed at the 40-min mark in some trials.
CONCLUSION
Preliminary evidence suggests IV ketamine as being safe and effective for the treatment of BD. Future studies should focus on investigating the effects of repeated acute and maintenance infusions using a randomized study design.
PubMed: 37771417
DOI: 10.1177/20451253231202723 -
Frontiers in Pharmacology 2024(, )- and ()-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However,... (Review)
Review
(, )- and ()-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However, they both have risks of psychomimetic effects, dissociative effects, and abuse liability, which limit their clinical use. Recent preclinical and clinical studies have shown that ()-ketamine has a more efficient and lasting antidepressant effect with fewer side effects compared to (, )- and ()-ketamine. However, a recent small-sample randomized controlled trial found that although ()-ketamine has a lower incidence of adverse reactions in adult TRD treatment, its antidepressant efficacy is not superior to the placebo group, indicating its antidepressant advantage still needs further verification and clarification. Moreover, an increasing body of research suggests that ()-ketamine might also have significant applications in the prevention and treatment of medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson's disease, multiple sclerosis, osteoporosis, substance use disorders, inflammatory diseases, COVID-19, and organophosphate poisoning. This article briefly reviews the mechanism of action and research on antidepressants related to ()-ketamine, fully revealing its application potential and development prospects, and providing some references and assistance for subsequent expanded research.
PubMed: 38666026
DOI: 10.3389/fphar.2024.1337749 -
L'Encephale Aug 2023Functional neurological disorder (FND) is a common cause of persistent and disabling neurological symptoms. Diagnostic delay may lead to no treatment, inappropriate... (Review)
Review
Functional neurological disorder (FND) is a common cause of persistent and disabling neurological symptoms. Diagnostic delay may lead to no treatment, inappropriate treatment or even iatrogenic symptoms. Yet, several treatments significantly reduce physical symptoms and improve functioning in FND patients even though not all patients respond to the currently available treatments. This review aims to describe the range of evidence-based rehabilitative and/or psychological therapeutic approaches available for FND patients. The most effective treatments are multidisciplinary and coordinated; using an outpatient or inpatient setting. Building a network of FND-trained healthcare professionals around the patient is an essential aspect of optimal patient management. Indeed, a supportive environment coupled with a collaborative therapeutic relationship improves understanding of FND and appears to help patients engage in appropriate treatments. Patients need to be invested in their own care and have to understand that recovery may depend on their commitment. The conventional treatment combines psychoeducation, physical rehabilitation and psychotherapy (cognitive and behavioral therapy, hypnosis, psychodynamic interpersonal therapy). Early referral of patients to physical therapy is recommended; however, the optimal parameters of treatment, duration and intensity are unknown and seem to vary with the severity and chronicity of symptoms. The goal is to minimize self-awareness by diverting attention or by stimulating automatically generated movements with non-specific and gradual exercises. The use of compensatory technical aids should be avoided as much as possible. Psychotherapeutic management should encourage self-evaluation of cognitive distortions, emotional reactions and maladaptive behaviors while empowering the patient in managing symptoms. Symptom management can use anchoring strategies to fight against dissociation. The aim is to connect to the immediate environment and to enrich one's sensoriality. The psychological interventions should then be adapted to the individual psychopathology, cognitive style and personality functioning of each patient. There is currently no known curative pharmacological treatment for FND. The pharmacological approach rather consists of progressively discontinuing medication that was introduced by default and that could lead to undesirable side effects. Finally, neurostimulation (transcranial magnetic stimulation, transcranial direct current stimulation) can be effective on motor FND.
Topics: Humans; Transcranial Direct Current Stimulation; Delayed Diagnosis; Conversion Disorder; Dissociative Disorders; Psychotherapy
PubMed: 37400332
DOI: 10.1016/j.encep.2023.06.005 -
Journal of Trauma & Dissociation : the... 2023The relationship between dissociation and cognitive abilities remains controversial. Empirical studies have reported positive, negative and non-existent associations...
INTRODUCTION
The relationship between dissociation and cognitive abilities remains controversial. Empirical studies have reported positive, negative and non-existent associations between dissociation and cognition. These inconsistent results may be due to the fact that the studies focused mainly on trait dissociation, while dissociation is not stable but transient. After validating the French version of the Clinician Administered Dissociative States Scale (CADSS), the aim of the present study was to evaluate the relationship between state dissociation and cognitive abilities.
METHOD
We recruited 83 patients suffering from post-traumatic stress disorder (PTSD) and assessed them twice. At T1, they performed a neutral Stroop task and a neutral binding task. At T2 (one to three weeks later), after a script-driven dissociative induction, they performed an emotional Stroop task and an emotional binding task. Between the two sessions, they completed questionnaires at home evaluating PTSD severity, trait dissociation and cognitive difficulties. State dissociation was assessed at T1 and T2 using the Clinician-Administered Dissociative States Scale (CADSS).
RESULTS
We found good psychometric properties of the French version of the CADSS. After inducing dissociation, significantly lower attentional performance was found among patients with than without dissociative reactions. We found a significant positive correlation between state dissociation and increased attention and memory difficulties after induction.
CONCLUSION
The French version of the CADSS is a reliable and valid tool to assess state dissociation, which is correlated with attentional difficulties. Attentional training is recommended to help patients control dissociative symptoms.
Topics: Humans; Stress Disorders, Post-Traumatic; Emotions; Dissociative Disorders; Anxiety; Attention
PubMed: 36992662
DOI: 10.1080/15299732.2023.2195397 -
European Neuropsychopharmacology : the... Sep 2023Esketamine, the S-enantiomer of ketamine, has recently emerged as a therapy for treatment-resistant depression (TRD), showing both rapid antidepressant action and good... (Observational Study)
Observational Study
Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study.
Esketamine, the S-enantiomer of ketamine, has recently emerged as a therapy for treatment-resistant depression (TRD), showing both rapid antidepressant action and good efficacy and high safety. It is also indicated for the acute short-term treatment of psychiatric emergency due to major depressive disorder (MDD) and for depressive symptoms in adults with MDD with acute suicidal thoughts/behavior. We here provide preliminary insights on esketamine nasal spray (ESK-NS) effectiveness and safety among patients with a substance use disorder (SUD) within the sample of patients with TRD collected for the observational, retrospective, multicentre REAL-ESK study. Twenty-six subjects were retrospectively selected according to the presence of a SUD in comorbidity. Subjects enrolled completed the three different follow-up phases (T0/baseline, T1/after one month, and T2/after three months) and there were no dropouts. A decrease in Montgomery-Asberg depression rating scale (MADRS) scores was recorded, thus highlighting the antidepressant efficacy of ESK-NS (MADRS decreased from T0 to T1, t = 6.533, df=23, p<0.001, and from T1 to T2, t = 2.029, df=20, p = 0.056). Considering tolerability and safety issues, one or more side effects were reported by 19/26 subjects (73%) after treatment administration. All reported side effects were time-dependent and did not cause significant sequelae; among them, dissociative symptoms (38%) and sedation (26%) were the most frequently reported. Finally, no cases of abuse or misuse of ESK-NS were reported. Despite study limitations related to the inherent nature of the study, a limited number of patients, and a short follow-up period, ESK-NS showed to be effective and safe in patients diagnosed with TRD comorbid with a SUD.
Topics: Adult; Humans; Administration, Intranasal; Antidepressive Agents; Comorbidity; Depression; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Drug-Related Side Effects and Adverse Reactions; Ketamine; Retrospective Studies; Substance-Related Disorders
PubMed: 37148637
DOI: 10.1016/j.euroneuro.2023.04.011 -
Alpha Psychiatry Mar 2024Substance use disorder (SUD) continues to pose a significant global health challenge, necessitating innovative and effective therapeutic interventions. Ketamine,... (Review)
Review
Substance use disorder (SUD) continues to pose a significant global health challenge, necessitating innovative and effective therapeutic interventions. Ketamine, traditionally recognized for its anesthetic properties, has emerged as a novel and promising avenue for the treatment of SUD. This narrative review critically examines the current body of literature surrounding the use of ketamine in various forms and settings for individuals grappling with substance abuse. The review explores the neurobiological underpinnings of ketamine's potential therapeutic effects in SUD, shedding light on its impact on glutamatergic neurotransmission, neuroplasticity, and reward pathways. Special attention is given to the psychotropic and dissociative properties of ketamine, exploring their implications for both therapeutic outcomes and patient experience. Ultimately, this review aims to provide a comprehensive overview of the current state of knowledge regarding ketamine's role in the treatment of SUD, emphasizing the need for further research and clinical exploration. As we navigate the complex terrain of addiction medicine, understanding the nuances of ketamine's potential in SUD holds promise for the development of more effective and personalized therapeutic strategies.
PubMed: 38798813
DOI: 10.5152/alphapsychiatry.2024.241522 -
Frontiers in Neuroscience 2023Psychotic treatment-resistant depression represents a complex and challenging form of mood disorder in clinical practice. Despite its severity, psychotic depression is...
Central nervous system-related safety and tolerability of add-on ketamine to standard of care treatment in treatment-resistant psychotic depression in patients with major depressive disorder and bipolar disorder.
BACKGROUND
Psychotic treatment-resistant depression represents a complex and challenging form of mood disorder in clinical practice. Despite its severity, psychotic depression is frequently underdiagnosed and inadequately treated. Ketamine has demonstrated rapid and potent antidepressant effects in clinical studies, while exhibiting a favorable safety and tolerability profile. Although there is limited literature available on the use of ketamine in psychotic TRD, reports on its efficacy, safety, and tolerability profile are of great interest to clinicians. The aim of this study is to investigate the relationship between dissociative symptomatology and psychomimetic effects in inpatients with treatment-resistant major psychotic depression and treatment-resistant bipolar psychotic depression, who receive intravenous ketamine treatment alongside psychotropic medication, both during and after treatment.
MATERIALS AND METHODS
A total of 36 patients diagnosed with treatment-resistant unipolar (17 patients) or bipolar (18 patients) depression with psychotic features were treated with eight intravenous infusions of 0.5 mg/kg ketamine twice a week over 4 weeks. Ketamine was given in addition to their standard of care treatment. The severity of depressive symptoms was evaluated using the MADRS, while dissociative and psychomimetic symptoms were assessed using the CADSS and BPRS, respectively.
RESULTS
There were no statistically significant changes observed in MADRS, CADSS, and BPRS scores within the study group during ketamine infusions. However, significant improvements in MADRS, CADSS, and BPRS scores were observed during ketamine infusions in both the unipolar and bipolar depression groups.
CONCLUSION
This study provides support for the lack of exacerbation of psychotic symptoms in both unipolar and bipolar depression.
PubMed: 37496742
DOI: 10.3389/fnins.2023.1214972 -
American Journal of TherapeuticsKetamine, an arylcyclohexylamine dissociative anesthetic agent, has evolved into a versatile therapeutic. It has a rapid-onset, well-understood cardiovascular effects...
BACKGROUND
Ketamine, an arylcyclohexylamine dissociative anesthetic agent, has evolved into a versatile therapeutic. It has a rapid-onset, well-understood cardiovascular effects and a favorable safety profile in clinical use. Its enantiomeric compound, esketamine, was approved by the Food and Drug Administration in 2019 for both treatment-resistant depression and major depressive disorder with suicidal ideation.
AREAS OF UNCERTAINTY
Research indicates dose-dependent impacts on cognition, particularly affecting episodic and working memory following both acute administration and chronic use, albeit temporarily for the former and potentially persistent for the latter. Alongside acute risks to cardiovascular stability, ketamine use poses potential liver toxicity concerns, especially with prolonged or repeated exposure within short time frames. The drug's association with "ketamine cystitis," characterized by bladder inflammation, adds to its profile of physiological risks.
THERAPEUTIC ADVANCES
Data demonstrate a single intravenous infusion of ketamine exhibits antidepressant effects within hours (weighted effect size averages of depression scores (N = 518) following a single 0.5 mg/kg infusion of ketamine is d = 0.96 at 24 hours). Ketamine is also effective at reducing posttraumatic stress disorder (PTSD) symptom severity following repeated infusions (Clinician-Administered PTSD Scale scores: -11.88 points compared with midazolam control). Ketamine also decreased suicidal ideation in emergency settings (Scale for Suicidal Ideation scores: -4.96 compared with midazolam control). Through its opioid-sparing effect, ketamine has revolutionized postoperative pain management by reducing analgesic consumption and enhancing recovery.
LIMITATIONS
Many studies indicate that ketamine's therapeutic effects may subside within weeks. Repeated administrations, given multiple times per week, are often required to sustain decreases in suicidality and depressive symptoms.
CONCLUSIONS
Ketamine's comprehensive clinical profile, combined with its robust effects on depression, suicidal ideation, PTSD, chronic pain, and other psychiatric conditions, positions it as a substantial contender for transformative therapeutic application.
Topics: Humans; Ketamine; Hallucinogens; Depressive Disorder, Major; Midazolam; Primary Health Care; Depression
PubMed: 38518272
DOI: 10.1097/MJT.0000000000001721 -
Cerebellum (London, England) Dec 2023The flocculus is a region of the vestibulocerebellum dedicated to the coordination of neck, head, and eye movements for optimal posture, balance, and orienting...
The flocculus is a region of the vestibulocerebellum dedicated to the coordination of neck, head, and eye movements for optimal posture, balance, and orienting responses. Despite growing evidence of vestibular and oculomotor impairments in the aftermath of traumatic stress, little is known about the effects of chronic psychological trauma on vestibulocerebellar functioning. Here, we investigated alterations in functional connectivity of the flocculus at rest among individuals with post-traumatic stress disorder (PTSD) and its dissociative subtype (PTSD + DS) as compared to healthy controls. Forty-four healthy controls, 57 PTSD, and 32 PTSD + DS underwent 6-min resting-state MRI scans. Seed-based functional connectivity analyses using the right and left flocculi as seeds were performed. These analyses revealed that, as compared to controls, PTSD and PTSD + DS showed decreased resting-state functional connectivity of the left flocculus with cortical regions involved in bodily self-consciousness, including the temporo-parietal junction, the supramarginal and angular gyri, and the superior parietal lobule. Moreover, as compared to controls, the PTSD + DS group showed decreased functional connectivity of the left flocculus with the medial prefrontal cortex, the precuneus, and the mid/posterior cingulum, key regions of the default mode network. Critically, when comparing PTSD + DS to PTSD, we observed increased functional connectivity of the right flocculus with the right anterior hippocampus, a region affected frequently by early life trauma. Taken together, our findings point toward the crucial role of the flocculus in the neurocircuitry underlying a coherent and embodied self, which can be compromised in PTSD and PTSD + DS.
Topics: Humans; Stress Disorders, Post-Traumatic; Emotions; Cerebellar Vermis; Hippocampus; Dissociative Disorders; Magnetic Resonance Imaging
PubMed: 36121553
DOI: 10.1007/s12311-022-01467-4