More than just joy: A qualitative analysis of participant experiences during nitrous oxide sedation.

BACKGROUND: Nitrous oxide use is shifting from general anesthesia to sedation and pain control. Interest in novel uses of nitrous oxide in psychiatry is also growing. Thus, understanding the consequences of using nitrous oxide remains relevant. Previous quantitative research might not have fully captured the whole spectrum of nitrous oxide, whereas qualitative analysis can provide a more comprehensive description. This qualitative study aims to describe the subjective experiences of nitrous oxide use in healthy volunteers who have no prior history of recreational substance misuse. METHODS: Twenty healthy male volunteers inhaled 50% nitrous oxide for 20 min. Females were excluded due to higher incidence of nausea with nitrous oxide. Afterwards, all participants answered an open-ended question about their experiences during sedation. The answers were then analyzed with inductive qualitative content analysis to identify emergent subcategories, categories, and overarching themes. RESULTS: We identified two themes: nitrous oxide is mind-altering and produces sensory overload. The mind-altering properties were represented by dreamlike states and heightened emotions. Dreamlike states comprised changes in consciousness and scary, bizarre, or transcendental dreams. Pleasant dreams were not reported. Heightened emotions included euphoria, anxiety, and fear of losing control. Sensory overload consists of distorted perception, bodily sensations, and a heightened sense of surroundings. CONCLUSIONS: Experiences under nitrous oxide sedation are extremely variable and not always pleasant. These findings can improve our understanding of the likes/dislikes of patients undergoing nitrous oxide sedation. Further qualitative studies should focus on the experiences of other groups, such as children or women in labor.

Electroconvulsive therapy increases temporarily plasma vascular endothelial growth factor in patients with major depressive disorder.

OBJECTIVES: Vascular endothelial growth factor (VEGF) has been related to the etiology of major depressive disorder (MDD). The findings involving the effects of electroconvulsive therapy (ECT) on the VEGF levels have been conflicting. The aim was to examine the possible changes in the VEGF levels and their associations with clinical outcome in patients with MDD during ECT. METHODS: The study comprised 30 patients suffering from MDD. Their plasma VEGF levels were measured at baseline and 2 and 4 hr after the first, fifth, and last ECT session. The severity of depression was quantified by the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: The VEGF levels increased between the 2-hr and 4-hr measurements during the first (p = .003) and the fifth (p = .017) sessions. The baseline VEGF levels between individual ECT sessions remained unchanged during the ECT series. No correlations were found between the increased VEGF levels and the clinical outcome. CONCLUSIONS: Electroconvulsive therapy increased the VEGF levels repeatedly at the same time point in two different ECT sessions. These increases had no association with the response to ECT. Consequently, VEGF may act as a mediator in the mechanism of action of ECT.

Threat-Modulation of Executive Functions-A Novel Biomarker of Depression?

Background: Alterations in executive functions, emotion regulation, and their interaction are common concomitants of depression. Executive dysfunction frequently lingers after treatment, has adverse effects on daily life, and predisposes to recurrence of depression. Yet, sensitive measures of executive function for reliable assessment of cognitive outcomes are still lacking in clinical practice. To better understand the impact of depression and its most effective treatment, electroconvulsive therapy (ECT), on cognition, we assessed executive functions pre- and post-ECT and whether objective measures reflecting alterations in emotion-executive function interaction correlate with depression severity or with cognitive outcome. Methods: Executive functions were assessed in 21 patients with major depressive disorder (MDD) before and after ECT using subjective measures from the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) and objective cognitive performance measures derived from computer-based test of executive function, Executive Reaction Time (RT) Test. In addition, we created novel indices reflecting emotional modulation of cognitive performance by subtracting different performance measures in the context of neutral distractors from those in the context of threat-related distractors. We correlated these indices with Beck Depression Inventory (BDI) and BRIEF-A scores. Results: Depression was significantly alleviated, and executive functions improved post-ECT, as seen in reduced BDI scores, BRIEF-A scores, and number of errors in Executive RT Test. Pre-ECT BDI scores correlated with threat modulation of RT (tmRT) and threat modulation of working memory (tmWM). Post-ECT tmRT correlated with several Behavioral Regulation scales and tmWM with several Metacognition scales of BRIEF-A. Conclusion: While caution is warranted, results from both subjective and objective measures suggest that ECT significantly improves executive functions and emotion regulation along with alleviation of depression. Novel indices derived from threat modulation of executive function and working memory show promise as objective biomarkers of depression severity pre-ECT and cognitive outcome post-ECT with potential for guiding depression treatments.

A Survey of Electroconvulsive Therapy in Finland.

OBJECTIVES: The purpose of this study was to explore the use of electroconvulsive therapy (ECT) in Finland in 2013. This included the rate of use, patient ages, sex, number of treatments, patient diagnoses, regional distribution, and availability of ECT. METHODS: A structured electronic questionnaire was used to collect data regarding the use of ECT from 21 Finnish hospital districts' 29 psychiatric ECT units. Data for comparison were collected from scientific publications concerning the use of ECT in Sweden, Norway, Denmark, and Estonia. RESULTS: Of 29 psychiatric ECT units, 25 (86%) responded. Electroconvulsive therapy was available in all except 1 hospital district, which used the services of another hospital district. Electroconvulsive therapy was administered to 1023 patients in total. The mean number of treatments per patient was 9.7. Twenty-three persons per 100,000 inhabitants received ECT. The ECT rate between hospital districts varied from 7.5 to 53.0 per 100,000 inhabitants. The mean number and median were 24.9 and 21.7 per 100,000 inhabitants, respectively. Maintenance therapy was administered to 27.1% of patients. Most (75%) of the ECT units indicated the capability to administer ECT to all patients who required it. The most common indications for ECT were major depression (38.4%), psychotic depression (30.9%), and bipolar disorder with depressive episodes (14.2%). CONCLUSIONS: Electroconvulsive therapy was available in every hospital district in Finland. In Finland, ECT was administered at approximately the same level as in Norway, Denmark, and Estonia (24, 32, and 28 per 100,000 inhabitants, respectively), but less than in Sweden (41 per 100,000 inhabitants).

Cortical Excitability and Activation of TrkB Signaling During Rebound Slow Oscillations Are Critical for Rapid Antidepressant Responses.

Rapid antidepressant effects of ketamine become most evident when its psychotomimetic effects subside, but the neurobiological basis of this "lag" remains unclear. Laughing gas (N2O), another NMDA-R (N-methyl-D-aspartate receptor) blocker, has been reported to bring antidepressant effects rapidly upon drug discontinuation. We took advantage of the exceptional pharmacokinetic properties of N2O to investigate EEG (electroencephalogram) alterations and molecular determinants of antidepressant actions during and immediately after NMDA-R blockade. Effects of the drugs on brain activity were investigated in C57BL/6 mice using quantitative EEG recordings. Western blot and qPCR were used for molecular analyses. Learned helplessness (LH) was used to assess antidepressant-like behavior. Immediate-early genes (e.g., bdnf) and phosphorylation of mitogen-activated protein kinase-markers of neuronal excitability-were upregulated during N2O exposure. Notably, phosphorylation of BDNF receptor TrkB and GSK3ß (glycogen synthase kinase 3ß) became regulated only gradually upon N2O discontinuation, during a brain state dominated by slow EEG activity. Subanesthetic ketamine and flurothyl-induced convulsions (reminiscent of electroconvulsive therapy) also evoked slow oscillations when their acute pharmacological effects subsided. The correlation between ongoing slow EEG oscillations and TrkB-GSK3ß signaling was further strengthened utilizing medetomidine, a hypnotic-sedative agent that facilitates slow oscillations directly through the activation of α2-adrenergic autoreceptors. Medetomidine did not, however, facilitate markers of neuronal excitability or produce antidepressant-like behavioral changes in LH. Our results support a hypothesis that transient cortical excitability and the subsequent regulation of TrkB and GSK3ß signaling during homeostatic emergence of slow oscillations are critical components for rapid antidepressant responses.

Effect of electroconvulsive therapy on brain-derived neurotrophic factor levels in patients with major depressive disorder.

OBJECTIVES: Brain-derived neurotrophic factor (BDNF) has been associated with depression and its treatment response. The aim of the present study was to explore the effect of electroconvulsive therapy (ECT) on serum and plasma BDNF levels and change of Montgomery-Asberg Depression Rating Scale (MADRS) and their associations in patients with major depressive disorder (MDD). METHODS: The study included thirty patients suffering from MDD. Their serum and plasma BDNF levels were examined before ECT (baseline) and after the first, fifth, and last ECT session. The severity of the depression and the response to ECT were measured with MADRS. RESULTS: Electroconvulsive therapy caused no significant changes in serum BDNF levels. Plasma BDNF levels decreased during the fifth ECT session between the baseline and the 2-hr samples (p = 0.019). No associations were found between serum or plasma BDNF levels and remission. The correlations between plasma and serum BDNF levels in each measurement varied between 0.187 and 0.636. CONCLUSIONS: Neither serum nor plasma BDNF levels were systematically associated with the clinical remission. However, the plasma BDNF levels somewhat varied during the ECT series. Therefore, the predictive value of BDNF for effects of ECT appears to be at least modest.

Reversible psychiatric adverse effects related to deep brain stimulation of the anterior thalamus in patients with refractory epilepsy.

OBJECTIVE: Anterior nucleus of thalamus (ANT) deep brain stimulation (DBS) is becoming a more common treatment for drug-resistant epilepsy. Epilepsy and depression display a bidirectional association. Anterior nucleus of thalamus has connections to anterior cingulate cortex and orbitomedial prefrontal cortex, hence, a possible role in emotional and executive functions, and thus, ANT DBS might exert psychiatric adverse effects. Our aim was to evaluate previous and current psychiatric symptoms in patients with epilepsy undergoing ANT DBS surgery and assess the predictability of psychiatric adverse effects. Programming-related psychiatric adverse effects are also reported. METHOD: Twenty-two patients with ANT DBS for retractable epilepsy were examined, and a psychiatric evaluation of depressive and other psychiatric symptoms was performed with Montgomery and Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and Symptom Checklist prior to surgery, concentrating on former and current psychiatric symptoms and medications. The follow-up visit was one year after surgery. RESULTS: At the group level, no changes on mood were observed during ANT DBS treatment. Two patients with former histories of depression experienced sudden depressive symptoms related to DBS programming settings; these were quickly alleviated after changing the stimulation parameters. In addition, two patients with no previous histories of psychosis gradually developed clear paranoid and anxiety symptoms that also relieved slowly after changing the programming settings. CONCLUSION: The majority of our ANT DBS patients did not experience psychiatric adverse effects. Certain DBS parameters might predispose to sudden depressive or slowly manifesting paranoid symptoms that are reversible via programming changes.

Low tumor necrosis factor-α levels predict symptom reduction during electroconvulsive therapy in major depressive disorder.

Objective: Changes in the tumor necrosis factor-α (TNFα) have been associated with major depressive disorder (MDD). Findings concerning the effects of electroconvulsive therapy (ECT) on the TNFα level have been contradictory. The aim was to examine the immediate and long-term changes in the TNFα level and their associations with symptom reduction in patients with MDD during ECT. Method: The study included 30 patients with MDD. Their TNFα levels were measured at baseline and 2 and 4 hr after the first, fifth and last ECT session. Depressive symptoms were assessed with the Montgomery-Asberg Depression Rating Scale (MADRS). Results: The TNFα level decreased from baseline to the 2- and 4-hr measurements. There was a correlation between the first ECT session TNFα levels and the relative symptom reduction according to the MADRS score after the ECT series. Both the first (baseline) ECT and 4-hr TNFα levels were lower in responders than in nonresponders. Conclusion: ECT consistently induced a decrease in the TNFα level after each studied session. A low TNFα level at the first ECT appeared to predict a symptom reduction. These findings suggest that TNFα might have a role in the pathogenesis in MDD and in the mechanism of action of ECT.

Meta-analysis of anxiety disorders and temperament.

BACKGROUND: The aims of the present study were to explore whether symptoms in different anxiety disorders are associated with Cloninger's model temperament dimensions novelty seeking (NS), harm avoidance (HA), reward dependence and persistence compared with control subjects in clinical samples of adults or late adolescents. METHOD: Literature search in the following databases: Cochrane Library, PubMed (Medline), Web of Science, Psycinfo and PsycArticles. Systematic review, grading the level of evidence and meta-analysis for each disorder by comparing the temperament dimension scores between patient and control samples in single studies. RESULTS: A total of 40 papers fulfilled the inclusion criteria. Meta-analyses were conducted on a total of 24 studies focusing on panic disorder (PD), social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD). The primary finding was a constant and clinically marked positive association between the HA temperament dimension and symptoms of PD, SAD and OCD, with a most marked effect in SAD, and a moderate effect in OCD and PD. Second, less marked and clinically marginal associations between NS score and SAD and OCD (negative associations), but no associations with PD were observed. The meta-analyses revealed heterogeneity between the results of individual studies, especially in the analyses including SAD and OCD. CONCLUSIONS: PD, SAD and OCD share a marked and state-dependent avoidant behavioral pattern, which is common for all anxiety disorders. However, PD showed a different pattern of arousal to novel stimuli from that of SAD and OCD. The findings are state dependent and based on cross-sectional studies.

Effects of S-ketamine as an anesthetic adjuvant to propofol on treatment response to electroconvulsive therapy in treatment-resistant depression: a randomized pilot study.

OBJECTIVE: Ketamine in electroconvulsive therapy (ECT) anesthesia has been reported to be associated with better seizure quality and longer duration compared with methohexital anesthesia. Furthermore, ketamine may enhance the efficacy of ECT while having rapid independent antidepressant properties itself. However, data on the effects of ketamine with ECT are inconsistent, and there are no reports of S-ketamine. The aim of the present pilot study was to explore the effects of S-ketamine as an adjuvant to propofol on the efficacy, seizure duration, and quality of electroencephalography in patients with treatment-resistant depression. METHODS: Thirty-two patients with a recurrent severe or psychotic major depressive disorder with treatment resistance to antidepressants were included in the study. For induction of anesthesia, the patients were randomized into 2 study groups. The S-ketamine group first received S-ketamine (0.4 mg/kg) as a bolus and then propofol. The treatment-as-usual group first received saline and then propofol. RESULTS: A statistically significant and clinically relevant reduction in the depression symptom scores was found in both study groups during ECT. There was no difference in the magnitude or speed of response between the study groups, nor was there any difference in the numbers of ECT treatments, seizure thresholds, seizure durations, and the electrical doses either. The patients recovered from anesthesia equally, but the degree of posttreatment disorientation and restlessness was more marked in the S-ketamine group. CONCLUSIONS: In conclusion, a subanesthetic adjuvant dose of S-ketamine with propofol may not increase the effects of ECT in patients with treatment-resistant depression. However, S-ketamine was associated with increased posttreatment disorientation and restlessness.

BDNF polymorphism rs11030101 is associated with the efficacy of electroconvulsive therapy in treatment-resistant depression.

The aim of the present study was to test for a possible association between two brain-derived neurotrophic factor (BDNF) polymorphisms (rs11030101 and rs61888800) and the efficacy of electroconvulsive therapy (ECT) [change in Montgomery-Åsberg Depression Rating Scale (MADRS)]. So far, there are no studies investigating an association between these polymorphisms and the efficacy of ECT. The patient sample included 119 patients with treatment-resistant major depressive disorder who were treated with ECT. BDNF polymorphism rs11030101, but not rs61888800, was associated with a change in the MADRS score. Patients with the TA genotype of rs11030101 were less likely to benefit from ECT compared with patients with the TT genotype (P=0.041). The finding suggests an association between BDNF polymorphism rs11030101 and the efficacy of ECT. Further studies with larger samples will be required to confirm this finding.