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The Journal of ECT Dec 2017A significant proportion of electroconvulsive therapy (ECT)-treated patients experience anxiety anticipating the treatment, often to such an extent that they refuse or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A significant proportion of electroconvulsive therapy (ECT)-treated patients experience anxiety anticipating the treatment, often to such an extent that they refuse or discontinue a much-needed treatment. Despite its great impact on treatment adherence, anxiety in patients receiving ECT is underexposed in the scientific literature.
OBJECTIVES
We aimed to review the prevalence and specific subjects of ECT-related anxiety and therapeutic interventions to reduce it.
METHODS
We performed a computerized search (EMBASE, MEDLINE, and PsycINFO) for articles meeting the following inclusion criteria: (1) qualitative (interview) studies, quantitative (questionnaire) studies, or experimental (interventional) studies that (2) report on anxiety that is related to a planned, ongoing, or past ECT treatment.
RESULTS
Of 1160 search results, 31 articles were included. Electroconvulsive therapy-related anxiety is estimated to be present in 14% to 75% of patients and is most often linked to worries about memory impairment or brain damage. Only a few interventions (chlorpromazine, meprobamate, propofol, a talking-through technique, an information leaflet, and animal-assisted therapy) have been proposed to reduce patients' ECT-related anxiety.
CONCLUSIONS
Electroconvulsive therapy-related anxiety is a highly prevalent phenomenon, and the literature provides little guidance for its clinical management. Most studies are of a low methodological quality and suffer from significant limitations, thereby hampering generalized conclusions. Given the clinical importance of ECT-related anxiety, further study on its nature and evolution through the course of treatment and on anxiety-reducing interventions is warranted.
Topics: Anxiety; Electroconvulsive Therapy; Humans; Prevalence
PubMed: 28009627
DOI: 10.1097/YCT.0000000000000383 -
International Journal of Molecular... Aug 2019From the past, we know how much "serendipity" has played a pivotal role in scientific discoveries. The definition of serendipity implies the finding of one thing while...
From the past, we know how much "serendipity" has played a pivotal role in scientific discoveries. The definition of serendipity implies the finding of one thing while looking for something else. The most known example of this is the discovery of penicillin. Fleming was studying "Staphylococcus influenzae" when one of his culture plates became contaminated and developed a mold that created a bacteria-free circle. Then he found within the mold, a substance that proved to be very active against the vast majority of bacteria infecting human beings. Serendipity had a key role in the discovery of a wide panel of psychotropic drugs as well, including aniline purple, lysergic acid diethylamide, meprobamate, chlorpromazine, and imipramine. Actually, many recent studies support a step back in current strategies that could lead to new discoveries in science. This change should seriously consider the idea that to further focus research project milestones that are already too focused could be a mistake. How can you observe something that others did not realize before you? Probably, one pivotal requirement is that you pay a high level of attention on what is occurring all around you. But this is not entirely enough, since, specifically talking about scientific discoveries, you should have your mind sufficiently unbiased from mainstream infrastructures, which normally make you extremely focused on a particular endpoint without paying attention to potential "unexpected discoveries". Research in medicine should probably come back to the age of innocence and avoid the age of mainstream reports that do not contribute to real advances in the curing of human diseases. Max Planck said "Science progresses not because scientists change their minds, but rather because scientists attached to erroneous views die, and are replaced", and Otto Warburg used the same words when he realized the lack of acceptance of his ideas. This editorial proposes a series of examples showing, in a practical way, how unfocused research may contribute to very important discoveries in science.
Topics: Chlorpromazine; Humans; Imipramine; Lysergic Acid Diethylamide; Meprobamate; Psychotropic Drugs
PubMed: 31443232
DOI: 10.3390/ijms20163973 -
Epilepsia Mar 2021Since 1955, several alkyl-carbamates have been developed for the treatment of anxiety and epilepsy, including meprobamate, flupirtine, felbamate, retigabine,... (Comparative Study)
Comparative Study Review
Since 1955, several alkyl-carbamates have been developed for the treatment of anxiety and epilepsy, including meprobamate, flupirtine, felbamate, retigabine, carisbamate, and cenobamate. They have each enjoyed varying levels of success as antiseizure drugs; however, they have all been plagued by the emergence of serious and sometimes life-threatening adverse events. In this review, we compare and contrast their predominant molecular mechanisms of action, their antiseizure profile, and where possible, their clinical efficacy. The preclinical, clinical, and mechanistic profile of the prototypical γ-aminobutyric acidergic (GABAergic) modulator phenobarbital is included for comparison. Like phenobarbital, all of the clinically approved alkyl-carbamates share an ability to enhance inhibitory neurotransmission through modulation of the GABA receptor, although the specific mechanism of interaction differs among the different drugs discussed. In addition, several alkyl-carbamates have been shown to interact with voltage-gated ion channels. Flupirtine and retigabine share an ability to activate K currents mediated by KCNQ (Kv7) K channels, and felbamate, carisbamate, and cenobamate have been shown to block Na channels. In contrast to other alkyl-carbamates, cenobamate seems to be unique in its ability to preferentially attenuate the persistent rather than transient Na current. Results from recent randomized controlled clinical trials with cenobamate suggest that this newest antiseizure alkyl-carbamate possesses a degree of efficacy not witnessed since felbamate was approved in 1993. Given that ceno-bamate's mechanistic profile is unique among the alkyl-carbamates, it is not clear whether this impressive efficacy reflects an as yet undescribed mechanism of action or whether it possesses a unique synergy between its actions at the GABA receptor and on persistent Na currents. The high efficacy of cenobamate is, however, tempered by the risk of serious rash and low tolerability at higher doses, meaning that further safety studies and clinical experience are needed to determine the true clinical value of cenobamate.
Topics: Anticonvulsants; Carbamates; Chlorophenols; Epilepsy; Humans; Tetrazoles; Treatment Outcome
PubMed: 33580520
DOI: 10.1111/epi.16832 -
Journal of Analytical Toxicology 2015A multidrug fatality involving sumatriptan is reported. Sumatriptan is a tryptamine derivative that acts at 5-HT(1B/1D) receptors and is used for the treatment of...
A multidrug fatality involving sumatriptan is reported. Sumatriptan is a tryptamine derivative that acts at 5-HT(1B/1D) receptors and is used for the treatment of migraines. The decedent was a 21-year-old white female found dead in bed by her spouse. No signs of physical trauma were observed and a large number of prescription medications were discovered at the scene. Toxicological analysis of the central blood revealed sumatriptan at a concentration of 1.03 mg/L. Following therapeutic dosing guidelines, sumatriptan concentrations do not exceed 0.095 mg/L. Sumatriptan was isolated by solid-phase extraction and analyzed using liquid chromatography-tandem mass spectrometry in multiple reaction monitoring mode. A tissue distribution study was completed with the following concentrations measured: 0.61 mg/L in femoral blood, 0.56 mg/L in iliac blood, 5.01 mg/L in urine, 0.51 mg/kg in liver, 3.66 mg/kg in kidney, 0.09 mg/kg in heart, 0.32 mg/kg in spleen, 0.01 mg/kg in brain, 15.99 mg/kg in lung and 78.54 mg/45 mL in the stomach contents. Carisoprodol, meprobamate, fluoxetine, doxylamine, orphenadrine, dextromethorphan and hydroxyzine were also present in the blood at the following concentrations: 3.35, 2.36, 0.63, 0.19, 0.06, 0.55 and 0.16 mg/L. The medical examiner ruled the cause of death as acute mixed drug toxicity and the manner of death as accident.
Topics: Autopsy; Carisoprodol; Chromatography, Liquid; Dextromethorphan; Doxylamine; Drug-Related Side Effects and Adverse Reactions; Evaluation Studies as Topic; Fatal Outcome; Female; Fluoxetine; Forensic Toxicology; Humans; Hydroxyzine; Liver; Meprobamate; Orphenadrine; Reproducibility of Results; Specimen Handling; Sumatriptan; Tandem Mass Spectrometry; Tissue Distribution; Young Adult
PubMed: 25324526
DOI: 10.1093/jat/bku120 -
Journal of Clinical Medicine Feb 2022Carisoprodol was authorised in 1959 without a full pharmacokinetic-pharmacodynamic (PK-PD) characterisation. We designed a crossover, double-blind, placebo-controlled,...
Single and Multiple Dose PK-PD Characterization for Carisoprodol. Part I: Pharmacokinetics, Metabolites, and 2C19 Phenotype Influence. Double-Blind, Placebo-Controlled Clinical Trial in Healthy Volunteers.
Carisoprodol was authorised in 1959 without a full pharmacokinetic-pharmacodynamic (PK-PD) characterisation. We designed a crossover, double-blind, placebo-controlled, randomized clinical trial to characterize the PKs of carisoprodol and its main active metabolite, meprobamate, after single (350 mg), multiple (350 mg/8 h, 14 days), and double (700 mg) doses of carisoprodol. Thirteen healthy volunteers were enrolled. After a single (350 mg) dose, the main carisoprodol parameters were (mean ± SD) Cmax: 2580 ± 1214 ng/mL, AUC: 8072 ± 6303 h·ng/mL, and half-life (T): 2 ± 0.8 h. For meprobamate, the parameters were Cmax: 2181 ± 605 ng/mL and 34,529 ± 7747 h·ng/mL y 9 ± 1.9 h. Different profiles were found for extensive and poor 2C19 metabolizers. After 14 days of treatment (350 mg/8 h) the results for carisoprodol were (mean ± SD) Cmax: 2504 ± 730 ng/mL, AUC: 7451 ± 3615 h·ng/mL, and T: 2 ± 0.7 h. For meprobamate (a steady state was reached), the parameters were Cmax: 5758 ± 1255 ng/mL and 79,699 ± 17,978 h·ng/mL y 8.7 ± 1.4 h. The study allowed for the full characterization of the pharmacokinetic profile of carisoprodol and meprobamate. Accumulation of meprobamate but not of carisoprodol was evident after 14 days of treatment.
PubMed: 35160309
DOI: 10.3390/jcm11030858