-
The Cochrane Database of Systematic... Aug 2019Catatonia is a debilitating disorder of movement and volition associated with schizophrenia and some other mental illnesses. People with catatonia are more likely to...
BACKGROUND
Catatonia is a debilitating disorder of movement and volition associated with schizophrenia and some other mental illnesses. People with catatonia are more likely to require hospitalisation and highly supervised care than those without the disorder. They also have an increased risk of secondary complications such as pneumonia, malnutrition and dehydration. The mainstay of treatment has been drug therapies and electroconvulsive therapy.
OBJECTIVES
To compare the effects of benzodiazepines with other drugs, placebo or electroconvulsive therapy for catatonia in people with schizophrenia or other similar serious mental illnesses (SMIs).
SEARCH METHODS
We updated our previous search (28 February 2007) by searching the Cochrane Schizophrenia Group's Study-Based Register of Trials (9 November 2016; 6 February 2019). This register is compiled by systematic searches of major resources (including CENTRAL, MEDLINE, Embase, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register. We also manually searched reference lists from studies selected by the search.
SELECTION CRITERIA
All controlled clinical trials that randomised people who have schizophrenia or other similar SMI and experiencing catatonia to receive benzodiazepines or another relevant treatment. We included studies that met our inclusion criteria and reported usable data. We excluded those not meeting our inclusion criteria or those not reporting usable data. We contacted authors when we required further information; and if we received no response, we put those studies aside as 'awaiting assessment'.
DATA COLLECTION AND ANALYSIS
Review authors extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis using a fixed-effect model. We completed a 'Risk of bias' assessment for the included study and generated a 'Summary of findings' table using GRADE.
MAIN RESULTS
The searches found 130 citations, from which we could identify 22 possibly relevant studies. From these, we could only include one study. This study had a relatively small sample size of 17 participants who received lorazepam or oxazepam and were drug free for one week before the trial started. The only usable data reported by this study were clinically important change in symptoms of catatonia measured as 50% improvement on the Visual Analogue Scale (VAS). There was no difference in the numbers of participants showing a clinically important change in their catatonic symptoms (RR 0.95, 95% CI 0.42 to 2.16; participants = 17; studies = 1; very low quality evidence).No data were reported for other important outcomes of hospital stay, clinically important change in satisfaction with care, global state, adverse effects or general functioningWe did find a few studies meeting our inclusion criteria but they reported no usable data. We had to exclude these. Although poorly reported, these studies do illustrate that relevant studies have been undertaken - they are not impossible to design and conduct.
AUTHORS' CONCLUSIONS
Analysis of the results from this review, which was a head-to-head comparison of two benzodiazepine monotherapies, does not show a clear difference in effect. No data were available for benzodiazepines compared to placebo or standard care. The lack of usable data and very low quality of data available makes it impossible to draw firm conclusions and further studies with a high-quality methodology and reporting are required in order to determine more definitively the outcomes associated with benzodiazepine use in the clinical management of catatonia in persons with schizophrenia and other SMI.
Topics: Antipsychotic Agents; Benzodiazepines; Catatonia; Electroconvulsive Therapy; Humans; Mental Disorders; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenia, Catatonic
PubMed: 31425609
DOI: 10.1002/14651858.CD006570.pub3 -
Tidsskrift For Den Norske Laegeforening... May 2019A woman in her fifties was admitted to hospital with decreased awareness and circulatory failure. She had been treated with left atrial cryoablation a few weeks before...
BACKGROUND
A woman in her fifties was admitted to hospital with decreased awareness and circulatory failure. She had been treated with left atrial cryoablation a few weeks before admission and had been cardioverted a few days after the procedure because of relapse of atrial fibrillation.
CASE PRESENTATION
On admission, the patient had systolic blood pressure of 80 mm Hg and an ECG with broad QRS-complexes at 380 ms. We suspected intoxication and she was intubated to administer activated charcoal after gastric lavage. She was cardiovascularly unstable and in need of intravenous infusion of noradrenaline and adrenaline. Further investigations at her home suggested that she had poisoned herself with 4-5 g flecainide, 0.3 g oxazepam and 0.5 g meclizine. After administration of 500 mmol sodium bicarbonate and 5 mmol calcium chloride, the QRS complexes narrowed temporarily. On day 2, due to sustained bradycardia and hypotension despite receiving adrenergic medications, a temporary pacemaker was implanted, leading to improved heart rate and blood pressure. She experienced several complications including hypertensive pulmonary oedema, atrial fibrillation, extensively prolonged QT interval because of polypharmacy and Takotsubo cardiomyopathy. She was discharged from the hospital in good health on day 17. At a follow-up visit at the outpatient clinic 12 weeks later, cardiac function had normalised. The QT interval was now normal; however, there were persistent T-wave inversions in leads I, aVL and V4-6.
INTERPRETATION
Flecainide blocks sodium channels in cardiomyocytes. Intoxication with flecainide is rare, with mortality rates of about 10 %. Sodium bicarbonate in larger doses has been reported to stabilise patients with flecainide intoxication due to modification of the binding of flecainide to sodium receptors in cardiomyocytes, and due to alkalisation which makes flecainide detach from sodium receptors. Our patient had a temporary effect with narrowing of QRS complexes after receiving sodium bicarbonate. She also showed a beneficial effect from implantation of a temporary pacemaker, although earlier case reports have described problems with high thresholds and capture failure.
Topics: Anti-Arrhythmia Agents; Charcoal; Drug Overdose; Electrocardiography; Female; Flecainide; Humans; Middle Aged; Pacemaker, Artificial; Shock; Sleepiness; Sodium Bicarbonate
PubMed: 31140247
DOI: 10.4045/tidsskr.18.0683 -
Chemosphere Jun 2019Pharmaceutical residues are polluting the surface water environments worldwide. Sewage and wastewater treatment, therefore, needs to be improved in order to remove...
Pharmaceutical residues are polluting the surface water environments worldwide. Sewage and wastewater treatment, therefore, needs to be improved in order to remove pharmaceutical residues from the effluent. One such treatment improvement is effluent ozonation. Even though ozonation has proven to be very efficient in reducing pharmaceutical parent compound concentrations in wastewater effluents, much remains unclear regarding potentially toxic ozonation by-product (OBP) formation. In this study, we sought to elucidate the aquatic toxicity of ozonated pharmaceuticals in zebrafish (Danio rerio) embryos in a static 144 h post fertilization (hpf) fish embryotoxicity (ZFET) assay. Three pharmaceuticals commonly detected in wastewater effluents, i.e. carbamazepine, diclofenac, and oxazepam, were selected for testing. Toxicity was assessed before and after 1 min ozonation (0.053 mg L peak O concentration) and 10 min ozonation (0.147 mg L peak O concentration). Chemical analysis showed that carbamazepine and diclofenac were largely removed by ozone (90 ± 11% and 97 ± 3.8%), whereas oxazepam was removed to a lesser extent (19 ± 5.7%). The ZFET assay revealed diverging toxicities. Diclofenac embryotoxicity decreased with increasing ozonation. Oxazepam did not cause embryotoxicity in the ZFET assay either pre- or post ozonation, but larvae swimming activity was affected at 144 hpf. Carbamazepine embryotoxicity, on the other hand, increased with increasing ozonation. Chemical analysis showed the formation of two OBPs (carbamazepine-10,11-epoxide and 10,11-dihydrocarbamazepine), possibly explaining the increased embryotoxicity. The results of this study highlight the importance of new chemical and toxicological knowledge regarding the formation of OBPs in post-ozonated effluents.
Topics: Animals; Carbamazepine; Diclofenac; Oxazepam; Ozone; Sewage; Water Pollutants, Chemical; Zebrafish
PubMed: 30875502
DOI: 10.1016/j.chemosphere.2019.03.034 -
South African Medical Journal =... Jan 2019Benzodiazepines (BZDs) are highly effective hypnotic and anxiolytic agents and among the most frequently used drugs in the world, but there are significant disadvantages...
BACKGROUND
Benzodiazepines (BZDs) are highly effective hypnotic and anxiolytic agents and among the most frequently used drugs in the world, but there are significant disadvantages associated with their use. Identifying possible irrational BZD prescribing is important to ensure safe and effective use of these agents. No studies have been conducted in other African countries, and this is the only study in the Western Cape (WC) Province of South Africa (SA), highlighting the paucity of local research.
OBJECTIVES
To identify the most commonly prescribed BZDs at a chronic dispensary unit (CDU) in the WC and describe the indications, co-prescribing patterns and patient factors in different areas of the WC.
METHODS
A retrospective, quantitative study was carried out using prescription data from a CDU in the Western Cape Department of Health, SA. Data for January 2017 were analysed. Associations between BZD therapeutic indications and co-prescribing patterns were assessed, together with demographic data. Data were coded and descriptive and inferential analysis was done using Stata version 14.
RESULTS
A total of 1 396 prescriptions met the inclusion criteria and were analysed. Overall, clonazepam was the most frequently prescribed BZD (n=691 prescriptions, 49.5%), followed by diazepam (n=298, 21.4%), lorazepam (n=222, 15.9%) and oxazepam (n=185, 13.3%). The most common therapeutic indication for BZDs was epilepsy (n=294, 21.1%), followed by depression (n=166, 11.9%) and depression with concomitant anxiety (n=79, 5.7%). The most common concomitant drug class associated with BZD use was antiepileptics (n=1 581), followed by other BZDs (n=706) and analgesics and antipyretics (n=665). Female patients were more likely than males to be prescribed BZDs (p<0.001), and the mean (standard deviation) age of BZD users was 51.3 (19.5) years.
CONCLUSIONS
BZDs were most commonly prescribed to female patients and middle-aged adults. Clonazepam was the most frequently prescribed BZD, indicating a preference for long-acting BZDs. Epilepsy was the most common therapeutic indication and antiepileptics were the most common concomitant drug class prescribed, implying that BZDs have a primary role in the management of epileptic conditions in the public healthcare sector. Future studies should include the private sector, as regulations in the public sector greatly influence the patterns of BZD use.
PubMed: 30834865
DOI: 10.7196/SAMJ.2019.v109i2.13347 -
Drug and Alcohol Dependence Apr 2019In a pilot study, intranasal oxytocin was demonstrated to reduce the benzodiazepine dose needed to relieve withdrawal symptoms during alcohol detoxification. The aim of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In a pilot study, intranasal oxytocin was demonstrated to reduce the benzodiazepine dose needed to relieve withdrawal symptoms during alcohol detoxification. The aim of the present study was to compare the effect of oxytocin and placebo during a three-day period of alcohol detoxification at an addiction treatment center in Norway.
METHODS
Randomized, double-blind, placebo-controlled trial with 40 patients fulfilling criteria for ICD-10 diagnosis of alcohol dependence (F10.2), admitted for alcohol detoxification and withdrawal treatment. The benzodiazepine oxazepam was given as symptom-triggered treatment based on the scores of the Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) scale. Participants were randomized to receive either intranasal oxytocin (24 IU twice daily) or placebo.
PRIMARY OUTCOME
Oxazepam dose required to complete a three-day course of detoxification.
SECONDARY OUTCOMES
Scores of the CIWA-Ar, the 10-item Hopkins Symptom Check List (HSCL-10), and self-reported total number of hours of sleep.
RESULTS
The mean total oxazepam dose (± standard deviation) was 56.8 ± 72.8 mg in the oxytocin group and 79.0 ± 122.9 in the placebo group (p = 0.490; difference -22.3 mg; 95% confidence interval (CI) -86.9 to +42.4 mg). The findings were inconclusive as to whether a difference in the CIWA-Ar score (5.94 ± 3.86 vs. 6.48 ± 3.92; p = 0.665) or in any of the other secondary outcomes was present. No serious adverse events were reported.
CONCLUSION
Compared to placebo, intranasal oxytocin did not significantly reduce the oxazepam dose needed to complete a 3-day course of alcohol detoxification and withdrawal treatment.
Topics: Administration, Intranasal; Adult; Alcoholism; Benzodiazepines; Double-Blind Method; Female; Humans; Male; Middle Aged; Norway; Oxazepam; Oxytocin; Pilot Projects; Substance Withdrawal Syndrome
PubMed: 30784955
DOI: 10.1016/j.drugalcdep.2019.01.003 -
The Science of the Total Environment May 2019Anthropogenic pharmaceutical pollutants have been detected in nature across the globe, and recent work has shown negative effects of pharmaceuticals on the health and...
Anthropogenic pharmaceutical pollutants have been detected in nature across the globe, and recent work has shown negative effects of pharmaceuticals on the health and welfare of many animals. However, whether alterations can be reversed has been poorly investigated, although such studies are essential to assess the effects of high-peak exposure events in waterways where pharmaceutical concentrations are usually low. In this study, we investigated the effects of two concentrations (environmentally relevant 1 μg L and high 100 μg L) of oxazepam, an anxiolytic commonly detected in aquatic environments, and whether behavioural alterations are reversible after depuration. Specifically, we measured daytime and night-time swimming activity and daytime behaviours related to boldness (foraging, sheltering and routine swimming activity) using the freshwater burbot (Lota lota). We found that both swimming activity and boldness were affected by oxazepam. Fish exposed to the higher level had a higher burst swimming duration (i.e., fast swimming bouts), both in the daytime and night-time trials. Further, fish exposed to the lower oxazepam level spent less time sheltering than control- and high-level exposed fish, but there was no difference between the control and high oxazepam treatments. For routine swimming activity, quantified in the boldness trials, and for latency to forage, there were no treatment effects. When retesting the fish after depuration, the detected behavioural alterations were no longer present. Since the magnitude of these effects were not consistent across endpoints, our study suggests that oxazepam might not be a great concern for this particular, stress tolerant, species, highlighting the importance of evaluating species-specific effects of pharmaceuticals. The observation that the effects we did find were reversible after depuration is encouraging, and indicates that rapid restoration of behaviours after removal from oxazepam contamination is possible.
Topics: Animals; Anti-Anxiety Agents; Behavior, Animal; Dose-Response Relationship, Drug; Feeding Behavior; Gadiformes; Oxazepam; Random Allocation; Swimming; Water Pollutants, Chemical
PubMed: 30772569
DOI: 10.1016/j.scitotenv.2019.02.049 -
Open Heart 2018In this study, we examined the effects of the routinely administration of benzodiazepines on reducing periprocedural anxiety versus no premedication.
AIMS
In this study, we examined the effects of the routinely administration of benzodiazepines on reducing periprocedural anxiety versus no premedication.
METHODS
In this open label study, we enrolled 1683 patients undergoing diagnostic coronary angiograms (CAG) or percutaneous coronary interventions (PCI). Randomisation was simulated by systematically allocating patients in monthly rotational periods to lorazepam 1 mg/sl, oxazepam 10 mg/po, diazepam 5 mg/po, midazolam 7.5 mg/po or . Anxiety was measured at four different time points using the one-item Visual Analogue Scale for Anxiety (VAS score) ranging from 0 to 10. The primary outcome was the difference in anxiety reduction (ΔVAS, preprocedure to postprocedure), between the different premedication strategies versus .
RESULTS
Anxiety reduction was larger in patients premedicated with lorazepam (ΔVAS=-2.0, SE=1.6, P=0.007) or diazepam (ΔVAS=-2.0, SE=1.5, p=0.003) compared with patients without any premedication (ΔVAS=-1.4, SE=1.2). The use of midazolam or oxazepam did not lead to a significant reduction in anxiety compared with patients who did not receive premedication. Additionally, a high number of patients treated with midazolam (N=39, 19.8%) developed side effects.
CONCLUSIONS
In this study, the use of lorazepam or diazepam was associated with a significant, but modest anxiety reduction in patients undergoing CAG or PCI. This study does not support the standard use of oxazepam or midazolam as premedication to reduce anxiety.
PubMed: 30275956
DOI: 10.1136/openhrt-2018-000833 -
Journal of Analytical Methods in... 2018A flow-through optosensing system for oxazepam recognition with fluorescence detection was performed by means of a molecular imprinted polymer based on its acid...
A flow-through optosensing system for oxazepam recognition with fluorescence detection was performed by means of a molecular imprinted polymer based on its acid hydrolysis product, 2-amino-5-chlorobenzophenone. The synthesis was conducted via a noncovalent imprinting methodology, using methacrylic acid as a functional monomer and ethylene glycol dimethacrylate as a cross-linking agent. Hydrolysis (types and concentration of acids), polymer retention capacity, binding properties, and elution (selectivity and reversibility) conditions were optimized. The selected molecular imprinted polymer had a molar ratio composition of 1 : 6 : 45 (template : functional monomer : cross-linker). The proposed method was applied to the determination of oxazepam in a pharmaceutical formulation. External standard calibration, standard additions calibration, and Youden's calibration were carried out in order to evaluate constant and proportional errors due to the matrix. The developed metabolite-based recognition system for benzodiazepines is an innovative procedure that could be followed in routine and quality control assays.
PubMed: 29850374
DOI: 10.1155/2018/6302609 -
PeerJ 2018The long-term use of benzodiazepines (BZD) and z-drugs in older populations is associated with a variety of sociodemographic and health-related factors. Recent studies...
INTRODUCTION
The long-term use of benzodiazepines (BZD) and z-drugs in older populations is associated with a variety of sociodemographic and health-related factors. Recent studies reported that long-term BZD and z-drugs use is associated with increased age, female sex, and severe negative psychological (e.g., depression) and somatic (e.g., chronic disease) factors. The current study explores the sociodemographic and health-related factors associated with long-term BZD and z-drugs use in the elderly.
METHODS
We conducted a cross-sectional survey among randomly selected patients of one health insurance plan ("AOK North-West") with BZD and z-drugs prescriptions in the past 12 months. The sample was stratified by appropriate German prescription guidelines (yes vs. no) and age (50-65 vs. >65 years). To examine the association of selected sociodemographic and psychological variables (e.g., sex, employment status, quality of life, depression) with long-term use, a binary logistic regression analysis was conducted.
RESULTS
In total, data from 340 patients were analyzed. The mean age was 72.1 ( = 14.5) years, and the most commonly used substances were zopiclon (38.1%), oxazepam (18.1%), and lorazepam (13.8%). The mean defined daily dose (DDD) was 0.73 ( = 0.47). Insomnia was the main reason for prescribing BZD and z-drugs. The long-term use of BZD and z-drugs was significantly associated with unemployment ( = 2.9, 95% CI [1.2-7.1]) and generally problematic medication use ( = 0.5, 95% CI [0.2-1.0]).
DISCUSSION
Unemployment status and problematic medication use had a significant association with the patient-reported, long-term use of BZD and z-drugs. Divergent prescription patterns might suggest problematic patterns of BZD and z-drugs use. The causal connection between the identified factors and problematic BZD and z-drugs prescription is not discussed in this paper. Nevertheless, employment status and possible evidence of general problematic drug use may be a warning signal to the prescribers of BZD and z-drugs.
PubMed: 29844949
DOI: 10.7717/peerj.4614 -
Frontiers in Psychiatry 2018Schizophreniform syndromes can be divided into primary idiopathic forms as well as different secondary organic subgroups (e.g., paraepileptic, epileptic, immunological,...
Schizophreniform syndromes can be divided into primary idiopathic forms as well as different secondary organic subgroups (e.g., paraepileptic, epileptic, immunological, or degenerative). Secondary epileptic explanatory approaches have often been discussed in the past, due to the high rates of electroencephalography (EEG) alterations in patients with schizophrenia. In particular, temporal lobe epilepsy is known to be associated with schizophreniform symptoms in well-described constellations. In the literature, juvenile myoclonic epilepsy has been linked to emotionally unstable personality traits, depression, anxiety, and executive dysfunction; however, the association with schizophrenia is largely unclear. We present the case of a 28-year-old male student suffering from mild myoclonic jerks, mainly of the upper limbs, as well as a predominant paranoid-hallucinatory syndrome with attention deficits, problems with working memory, depressive-flat mood, reduced energy, fast stimulus satiation, delusional and audible thoughts, tactile hallucinations, thought inspirations, and severe sleep disturbances. Cerebral magnetic resonance imaging and cerebrospinal fluid analyses revealed no relevant abnormalities. The routine EEG and the first EEG after sleep deprivation (under treatment with oxazepam) also returned normal findings. Video telemetry over one night, which included a partial sleep-deprivation EEG, displayed short generalized spike-wave complexes and polyspikes, associated with myoclonic jerks, after waking in the morning. Video-EEG monitoring over 5 days showed over 100 myoclonic jerks of the upper limbs, frequently with generalized spike-wave complexes with left or right accentuation. Therefore, we diagnosed juvenile myoclonic epilepsy. This case report illustrates the importance of extended EEG diagnostics in patients with schizophreniform syndromes and myoclonic jerks. The schizophreniform symptoms in the framework of epileptiform EEG activity can be interpreted as a (para)epileptic mechanism due to local area network inhibition (LANI). Following the LANI hypothesis, paranoid hallucinatory symptoms are not due to primary excitatory activity (as myoclonic jerks are) but rather to the secondary process of hyperinhibition triggered by epileptic activity. Identifying subgroups of schizophreniform patients with comorbid epilepsy is important because of the potential benefits of optimized pharmacological treatment.
PubMed: 29780332
DOI: 10.3389/fpsyt.2018.00161