- Seizure Occurring During Baclofen Monotherapy for Phenibut Withdrawal. [Journal Article]Clin Neuropharmacol. 2023 Feb 04 [Online ahead of print]CN
- CONCLUSIONS: Phenibut use is rising, and treatment options for PW, such as baclofen, warrant additional study. Potential risks of underdosing baclofen if used as monotherapy in PW may include seizures as withdrawal progresses. Baclofen's role in therapy may be more appropriate as an adjunct than a cornerstone of therapy. Treatment done in consultation with providers experienced in managing withdrawal such as a toxicologist may help reduce this risk.
- Effects of tranquilization therapy in elderly patients suffering from chronic non-communicable diseases: A meta-analysis. [Meta-Analysis]Acta Pharm. 2023 Mar 01; 73(1):43-57.AP
- The current meta-analysis searched the literature connected to different tranquilizers used to treat elderly people and assessed it in terms of dose, types of outcomes and adverse effects, to determine a safe and acceptable tranquilizer and its optimal dose. A systematic literature review was undertaken for randomized controlled trials, case-control, retrospective and prospective studies on the u…
The current meta-analysis searched the literature connected to different tranquilizers used to treat elderly people and assessed it in terms of dose, types of outcomes and adverse effects, to determine a safe and acceptable tranquilizer and its optimal dose. A systematic literature review was undertaken for randomized controlled trials, case-control, retrospective and prospective studies on the use of tranquilizers in elderly patients, using PubMed, Ebsco, SCOPUS and Web of Science. PICOS criteria were used to select studies, and pertinent event data was collected. This meta-analysis includes 16 randomized control trials spanning the years 2000 to 2022, using the data from 2224 patients. The trials that were included used various tranquilizers such as diazepam, alprazolam, temazepam and lorazepam, and indicated high treatment efficacy and low adverse effects. With a p-value of 0.853 for Egger's test and 0.13 for Begg's test, the current meta-analysis shows a minimal probability of publication bias. A recent meta-analysis supports the use of tranquilizers in older people to treat sleeplessness, epilepsy or anxiety, but only at modest doses, because large doses are harmful and produce numerous withdrawal symptoms.
- Postpartum Collapse Subsequent to Catatonia in a Female with COVID-19 Infection: a Rare Entity Visited. [Case Reports]J Obstet Gynaecol India. 2023 Jan 10 [Online ahead of print]JO
- Postpartum collapse is a life-threatening condition caused by obstetrical and non-obstetrical events. In this case report, we discuss a case of postpartum collapse in COVID-19-positive woman who required intensive care and mechanical ventilation for two days. After confusing collision of many provisional diagnoses soldiering for three days, she was ultimately diagnosed with malignant catatonia. T…
Postpartum collapse is a life-threatening condition caused by obstetrical and non-obstetrical events. In this case report, we discuss a case of postpartum collapse in COVID-19-positive woman who required intensive care and mechanical ventilation for two days. After confusing collision of many provisional diagnoses soldiering for three days, she was ultimately diagnosed with malignant catatonia. Targeted therapy with lorazepam challenge resulted in drastic improvement, and she was discharged with her baby in healthy condition.
- Recurrent Catatonia: Infection and Immunity in an Idiopathic Illness. [Case Reports]J Psychiatr Pract. 2023 01 01; 29(1):82-89.JP
- Catatonia can be associated with multiple physical and mental illnesses, and idiopathic catatonia is a well-recognized clinical entity. Here we report a case of recurrent idiopathic catatonia with underlying immunologic abnormalities, with an emphasis on etiological hypotheses. An 18-year-old female with mild learning disability, dyspraxia, autoimmune hypothyroidism, and nonceliac gluten intolera…
Catatonia can be associated with multiple physical and mental illnesses, and idiopathic catatonia is a well-recognized clinical entity. Here we report a case of recurrent idiopathic catatonia with underlying immunologic abnormalities, with an emphasis on etiological hypotheses. An 18-year-old female with mild learning disability, dyspraxia, autoimmune hypothyroidism, and nonceliac gluten intolerance was referred to mental health services after developing an episode of catatonia following tonsillitis. She had experienced 2 previous episodes suggestive of catatonia, one of which developed after a snakebite and the other after a viral infection. Samples of cerebrospinal fluid and whole blood tested positive for human herpesvirus (HHV) on DNA-polymerase chain reaction testing during her third episode, but the patient had no signs of encephalitis. She responded well to lorazepam but developed significant side effects with low-dose olanzapine and aripiprazole. She returned to her usual baseline with medical management. Very little is known about possible etiologies of recurrent idiopathic catatonia. An atypical response to an HHV infection is a likely cause of one of the episodes in this case. There is substantial evidence connecting immune dysregulation to mental illnesses. Proinflammatory effects of latent HHV, proinflammatory genetic polymorphisms related to learning disability, and autoimmune dysfunction are likely factors that may have contributed to the development of recurrent catatonia following external antigen exposure in this case. Future research should focus on immune-mediated etiologies of catatonia, the role of immunotherapy in the treatment of idiopathic catatonia, and systems research to improve multidisciplinary management of neuropsychiatric disorders.
- The development and validation of a prediction model of lithium carbonate blood concentration by artificial neural network: a retrospective study. [Journal Article]Ann Palliat Med. 2022 Dec; 11(12):3718-3726.AP
- CONCLUSIONS: The correlation, accuracy, and precision of ANN prediction are worthy to be further investigated to predict the blood concentration of Li carbonate.
- Expanded table: Some oral drugs for chronic insomnia. [Journal Article]Med Lett Drugs Ther. 2023 Jan 09; 65(1667):e6-e10.ML
- Evaluation of intravenous lorazepam dosing strategies and the incidence of refractory status epilepticus. [Journal Article]Epilepsy Res. 2022 Dec 22; 190:107067.ER
- CONCLUSIONS: The majority of patients in the study received less than the recommended dose of IV lorazepam for SE. Patients who received less than 4 mg experienced an increased progression to RSE, which supports current guideline recommended dosing. While there was an increased rate of mortality in patients who received 4 mg compared to less than 4 mg, time in SE was prolonged in the patient population and severity of illness was only available for a limited number of patients included.
- Behavioral restriction, lorazepam, and escitalopram uniquely influence the expression of naturalistic stereotypy in deer mice: perspectives on anxiety- and compulsive-like behavior. [Journal Article]Front Behav Neurosci. 2022; 16:1071157.FB
- Introduction: Stereotypical expression in laboratory-housed rodents can be explained by different motivational, coping, and motor dysfunction theories. Here, we aimed to explore the neurocognitive underpinnings of high stereotypical (HS) expression in deer mice (Peromyscus maniculatus bairdii), previously proposed as a model system of compulsive-like behavioral persistence. Specifically, we aimed…
Introduction: Stereotypical expression in laboratory-housed rodents can be explained by different motivational, coping, and motor dysfunction theories. Here, we aimed to explore the neurocognitive underpinnings of high stereotypical (HS) expression in deer mice (Peromyscus maniculatus bairdii), previously proposed as a model system of compulsive-like behavioral persistence. Specifically, we aimed to establish whether HS behavior is related to an underlying escape-related trigger. Methods: One-hundred and sixteen deer mice were classified as either non-stereotypical (NS) or HS. Mice of each cohort were further subdivided and exposed to either sub-acute (3-day) or chronic (25-day) behavioral restriction (R), and high-dose escitalopram (ESC), lorazepam (LOR), alone and in combination with R (ESC+R and LOR+R, respectively). Mice were reassessed for stereotypical behavior at both time points. Results: Our results indicate that HS behavior is likely not temporally and functionally related to an anxiogenic trigger, i.e., R, but rather that HS is associated with parallel changes in anxiogenic feedback processing. We also show that chronic R alone significantly decreased the time spent in expressing HS behavior in animals of the HS, but not NS phenotype. Discussion: This points to the possibility that HS-expressing mice represent a subgroup of P. maniculatus bairdii in which unique interactions between neurobiology and processes of gradual behavioral organization, may contribute to the expression of the typical behaviors observed in this cohort. Collectively, our findings highlight the value of the deer mouse model system to investigate the potential neurocognitive mechanisms that may underlie the development of persistent phenotypes that can likely not be explained entirely by current theories.
- The management challenges of a case with Flupentixol-induced neuroleptic malignant syndrome. [Case Reports]Neuropsychopharmacol Rep. 2022 Dec 30 [Online ahead of print]NR
- CONCLUSIONS: In conclusion, there were suggestions for the management challenges of NMS in patients receiving LA injectable antipsychotic agents.
- Catatonia and Delirium: Assessment of Comorbidity, Prevalence, and Therapeutic Response in Medically Ill Inpatients From a University Hospital. [Journal Article]J Clin Psychopharmacol. 2023 Jan-Feb 01; 43(1):55-59.JC
- CONCLUSIONS: This is the first study on lorazepam use in catatonia-delirium patients; however, further studies are needed to determine the safety and efficacy of lorazepam in these patients. Catatonia and catatonia/delirium are underdiagnosed in inpatient wards and should be routinely assessed in patients with an altered mental status.
- Physiologically Based Pharmacokinetic Modelling to Identify Physiological and Drug Parameters Driving Pharmacokinetics in Obese Individuals. [Journal Article]Clin Pharmacokinet. 2022 Dec 26 [Online ahead of print]CP
- CONCLUSIONS: Both physiological changes and drug properties impact drug pharmacokinetics in obese subjects. Clearance increases due to enhanced hepatic and renal blood flows. Volume of distribution is higher for all drugs, with differences among drugs depending on their pKa/logP.
- Dexmedetomidine sublingual film (Igalmi) for acute agitation. [Journal Article]Med Lett Drugs Ther. 2022 12 26; 64(1666):203-205.ML
- Pain, Nausea, and Hospital Admission after Uterine Fibroid Embolization: A Comparison of 2 Protocols. [Journal Article]J Vasc Interv Radiol. 2022 Dec 13 [Online ahead of print]JV
- Uterine fibroid embolization (UFE) procedures performed from 2013 to 2019 were reviewed. Seventy-two patients were treated with a standard protocol consisting of sedation, ketorolac, ondansetron, and overnight parenteral analgesics and antiemetics. Ninety-six patients were treated with a new protocol, which added transdermal scopolamine, lorazepam, and intravenous acetaminophen. Outpatient uterin…
Uterine fibroid embolization (UFE) procedures performed from 2013 to 2019 were reviewed. Seventy-two patients were treated with a standard protocol consisting of sedation, ketorolac, ondansetron, and overnight parenteral analgesics and antiemetics. Ninety-six patients were treated with a new protocol, which added transdermal scopolamine, lorazepam, and intravenous acetaminophen. Outpatient uterine fibroid embolization (OP-UFE) not requiring hospitalization was successful in 81.4% and 2.7% of patients treated with the new and old protocols, respectively (odds ratio [OR], 141.4; P < .0001). Procedural fentanyl doses were lower with the new protocol than with the old one (mean, 148 vs 186 mcg; P = .0016). In the new protocol subset, patients were 1.01 times more likely to fail OP-UFE for every microgram increase in procedural fentanyl (OR, 0.99, P = .009), and those presenting with pain were less likely to succeed with OP-UFE than those with bleeding or bulk symptoms (OR, 0.31, P = .04). In conclusion, decreasing the opioid dose while increasing the antiemetic and nonopioid analgesic medications improves the chances of same day discharge after UFE.
- The anti-anxiety drug lorazepam changes implicit behaviors but not explicit evaluations of sense of agency under authoritative pressure: A functional magnetic resonance imaging study. [Journal Article]Front Psychol. 2022; 13:991357.FP
- Previous research on coercion has neglected the fact that agents under authoritative pressure may also suffer from coercive power, which can trigger anxiety-like emotional negativity on its victims. Furthermore, high levels of neuroticism and/or anxiety have been found to be associated with the compliance of various forms of social pressure. In this study, we investigate the effects of the anxiol…
Previous research on coercion has neglected the fact that agents under authoritative pressure may also suffer from coercive power, which can trigger anxiety-like emotional negativity on its victims. Furthermore, high levels of neuroticism and/or anxiety have been found to be associated with the compliance of various forms of social pressure. In this study, we investigate the effects of the anxiolytic GABA A (gamma-Aminobutyric acid) modulator, lorazepam, on behavioral and neural responses to coercive power. Here, we applied a virtual obedience to authority paradigm alongside lorazepam administration (versus placebo), and during functional magnetic resonance imaging scanning. Our results show that lorazepam administration exerted differential effects on the reaction times (RTs) when initiating harming versus helping behaviors, with longer harming RTs compared to helping RTs, despite comparable subjective ratings regarding perceived coercion. Coercive harming significantly increased activity in the amygdala, hippocampus, orbitofrontal cortex, and dorsolateral prefrontal cortex (dlPFC). Lorazepam administration decreased amygdala and hippocampus activity, but increased dlPFC and right temporoparietal junction activations. The lower activity in the hippocampus predicted higher ratings for perceived coercion. Furthermore, lorazepam significantly decreased the functional connectivity of the hippocampus with the dlPFC during coercive harming. In conclusion, we provide evidence -by incorporating multimodal indices, including neuroimaging, neuropharmacological interventions, and behavioral assessments- to posit that the GABA A agonist, lorazepam, might aid as a possible intervention in service of coping strategies against coercion.
- Novel variants in GABAA receptor subunits: A possible association with benzodiazepine resistance in patients with drug-resistant epilepsy. [Journal Article]Epilepsy Res. 2023 Jan; 189:107056.ER
- Benzodiazepines (BDZ) such as diazepam and lorazepam are popular as first-line treatment for acute seizures due to their rapid action and high efficacy. However, long-term usage of BDZ leads to benzodiazepine resistance, a phenomenon whose underlying mechanisms are still being investigated. One of the hypothesised mechanisms contributing to BDZ resistance is the presence of mutations in benzodiaz…
Benzodiazepines (BDZ) such as diazepam and lorazepam are popular as first-line treatment for acute seizures due to their rapid action and high efficacy. However, long-term usage of BDZ leads to benzodiazepine resistance, a phenomenon whose underlying mechanisms are still being investigated. One of the hypothesised mechanisms contributing to BDZ resistance is the presence of mutations in benzodiazepine-sensitive receptors. While a few genetic variants have been reported previously, knowledge of relevant pathogenic variants is still scarce. We used Sanger Sequencing to detect variants in the ligand-binding domain of BDZ-sensitive GABAA receptor subunits α1-3 and 5 expressed in resected brain tissues of drug-resistant epilepsy (DRE) patients with a history of BDZ resistance and found two previously unreported predicted pathogenic frameshifting variants - NM_000807.4(GABRA2):c.367_368insG and NM_000810.4(GABRA5):c.410del - significantly enriched in these patients. The findings were further explored in resected DRE brain tissues through cellular electrophysiological experiments.
- Focal status epilepticus: a review of pharmacological treatment. [Review]Neurologia (Engl Ed). 2022 Nov-Dec; 37(9):757-766.N
- CONCLUSIONS: The available scientific evidence is insufficient to claim that pharmacological treatment of focal SE should be different from treatment for generalised SE. More studies with a greater number of patients are needed.
- Use of Alcohol, Cannabinoids, Psychostimulants, and Sedatives before and during the COVID-19 Pandemic among Students in 40 European Countries. [Journal Article]Int J Environ Res Public Health. 2022 11 12; 19(22)IJ
- In March 2020, the WHO announced the COVID-19 pandemic, which has been ongoing for over 2 years. To stop the spread of the virus, the governments of many countries decided to introduce reasonable social restrictions that were suitable for pandemic waves. This led to radical changes in people's lives, especially among students, who are very active in society. Before COVID-19, being of student age …
In March 2020, the WHO announced the COVID-19 pandemic, which has been ongoing for over 2 years. To stop the spread of the virus, the governments of many countries decided to introduce reasonable social restrictions that were suitable for pandemic waves. This led to radical changes in people's lives, especially among students, who are very active in society. Before COVID-19, being of student age was associated with the highest frequency of stimulants use. It is important to note that drugs are taken disparately in various areas. Therefore, using the Computer-Assisted Web Interview type of study, the impact of the pandemic on the use of alcohol, cannabinoids, psychostimulants (e.g., amphetamine, methamphetamine, ecstasy) and sedatives (e.g., zolpidem, zopiclone, alprazolam, lorazepam, etc.) was assessed among students from European countries. The questionnaire included single- and multiple-answer questions. The first part concerned sociodemographic questions, while the second included questions about the use of stimulants in the last 3 months prior to participation in the study. Distribution of the survey covered the period from 31 January 2016 to 30 April 2021. A total of 17,594 European students participated in the study. The vast majority of participants were women (80.4%) and students of non-medical universities (77.2%) living in Eastern European countries (86.1%). Of all students, 15,613 (89.6%) reported alcohol drinking, 2538 (14.1%) the use of cannabinoids, 650 (3.6%) psychostimulants, and 2252 (12.5%) sedatives in the past three months. It has been shown that women are far less likely to use alcohol (OR 0.81), psychostimulants (OR 0.44) and cannabinoids (OR 0.49), while they are more likely to use sedatives (OR 1.41). During the COVID-19 pandemic, the consumption of alcohol (OR 0.55) and psychostimulants (OR 0.72) decreased and that of sleep medications increased (OR 1.17). To conclude, the COVID-19 pandemic influenced the pattern of stimulants used by students in European countries. The restriction of social interactions contributed to the decrease in the consumption of alcohol and psychostimulants but increased the use of sedatives and the frequency of their use. Women were found to use sedatives more often, while men preferred to drink alcohol and use cannabinoids or psychostimulants. It has also been shown that students of Central and Eastern Europe more often use alcohol and sedatives, while in Southern European countries psychostimulants and cannabinoids are preferred.
- StatPearls: Lorazepam [BOOK]StatPearls. StatPearls Publishing: Treasure Island (FL)BOOK
- Lorazepam is a benzodiazepine medication commonly used as the sedative and anxiolytic of choice in the inpatient setting owing to its fast (1 to 3 minute) onset of action when administered intravenously. Lorazepam is also one of the few sedative-hypnotics with a relatively clean side effect profile. This activity covers lorazepam, including mechanism of action, pharmacology, adverse event profile…
Lorazepam is a benzodiazepine medication commonly used as the sedative and anxiolytic of choice in the inpatient setting owing to its fast (1 to 3 minute) onset of action when administered intravenously. Lorazepam is also one of the few sedative-hypnotics with a relatively clean side effect profile. This activity covers lorazepam, including mechanism of action, pharmacology, adverse event profiles, eligible patient populations, monitoring, and highlights the interprofessional team's role in managing lorazepam therapy.
- [Acute catatonia]. [Review]Nervenarzt. 2023 Feb; 94(2):106-112.N
- CONCLUSIONS: Several factors lead to the underdiagnosis of catatonia. It is problematic that even life-threatening malignant catatonia is often not recognized as such, although there is a mortality of about 50% if untreated. The best treatment outcome is achieved with a combination of benzodiazepines and ECT. The treatment of severe malignant catatonia represents an emergency indication for ECT.
- Management of status epilepticus in childhood: a survey conducted at pediatric hospitals in the City of Buenos Aires. [Journal Article]Arch Argent Pediatr. 2022 Nov 24 [Online ahead of print]AA
- Introduction. Status epilepticus is the most common neurological emergency. Although mortality in children is low, morbidity may exceed 20%. Objective. To evaluate the management of status epilepticus by pediatricians who usually treat this condition. Population and methods. Descriptive, cross-sectional study based on a survey administered to physicians from 3 pediatric hospitals in the City of B…
Introduction. Status epilepticus is the most common neurological emergency. Although mortality in children is low, morbidity may exceed 20%. Objective. To evaluate the management of status epilepticus by pediatricians who usually treat this condition. Population and methods. Descriptive, cross-sectional study based on a survey administered to physicians from 3 pediatric hospitals in the City of Buenos Aires. Results. A total of 292 surveys were administered (complete response rate as high as 86%); 77% were administered to pediatricians and 16% to intensive care specialists. Forty-seven percent of the participants reported that they administer the first dose of a benzodiazepine within the correct timeframe; 56% use intrarectal diazepam when intravenous access is not available; 95% choose lorazepam as the initial benzodiazepine if an intravenous line is available; 58% initiate the administration of a second-line drug within the correct timeframe; 84% administer phenytoin as the first-choice, second-line drug; and 33% do not measure treatment time. Overall adherence to international recommendations was 17%. Conclusions. Our study highlights poor adherence of pediatricians to international guidelines, particularly in time-dependent decisions. Greater heterogeneity was observed in treatment approaches as the treatment algorithm progressed.
- Tracheotomy in ventilator-dependent patients with COVID-19: a cross-sectional study of analgesia and sedative requirements. [Journal Article]J Int Med Res. 2022 Nov; 50(11):3000605221138487.JI
- CONCLUSIONS: When appropriate personal protective equipment is available, use of tracheotomy in patients with COVID-19 who require MV may help to conserve medication supplies in times of extreme shortages.
- The Prevalence of Atypical Antipsychotics, Antidepressants, and Benzodiazepines Use in Dementia Patients in King Abdulaziz Medical City. [Journal Article]Cureus. 2022 Oct; 14(10):e30460.C
- Background Dementia is a major neuropsychiatric disease defined by a progressive decline in cognitive functions. Atypical antipsychotics, antidepressants, and benzodiazepines are mainly prescribed for dementia. Many dementia pharmacological management options are associated with serious health risks. Therefore, this study aimed to determine the prevalence of antipsychotic, antidepressant, and ben…
Background Dementia is a major neuropsychiatric disease defined by a progressive decline in cognitive functions. Atypical antipsychotics, antidepressants, and benzodiazepines are mainly prescribed for dementia. Many dementia pharmacological management options are associated with serious health risks. Therefore, this study aimed to determine the prevalence of antipsychotic, antidepressant, and benzodiazepine use in dementia patients in King Abdulaziz Medical City. Methodology A cross-sectional study was conducted at a tertiary hospital (King Abdulaziz Medical City, Jeddah) between December 2016 and January 2019. The participants were patients over the age of 65 years diagnosed with dementia. Data were collected from the medical records of the hospital after acquiring ethical approval. Patients with psychiatric diseases preceding the diagnosis of dementia, or patients with dementia-like symptoms as a side effect of any medications were excluded. The variables included were demographics, dementia subtypes, medications, and the presence or absence of chronic diseases. Results This study included 139 patients of whom 51.1% were males. The mean age was 82.8 ± 8.8 years. Moreover, 34.53% of the patients were prescribed medications for dementia management. Importantly, medications prescribed for dementia were classified as the following: atypical antipsychotics (20.86%), antidepressants (17.3%), and benzodiazepines (5%). The most commonly prescribed atypical antipsychotics were quetiapine (93.1%), risperidone (13.8%), and olanzapine (3.44%). For antidepressants, the most commonly prescribed medications for dementia were mirtazapine (62.5%), citalopram (45.8%), amitriptyline (8.3%), and paroxetine (4.2%). Moreover, most prescriptions for benzodiazepine were divided between lorazepam (71.4%), clonazepam (14.3%), and diazepam (14.3%). Conclusions This study's results were consistent with previous epidemiological studies that have been conducted worldwide regarding the increase in the use of antipsychotics and antidepressants, with the exception of benzodiazepines. To our knowledge, there is a lack of research regarding the medications prescribed in the geriatrics age group with dementia. Therefore, the outcomes of this study recommend initiating awareness campaigns among physicians, regarding the harm of using antipsychotics, especially for this age group. Lastly, future studies should focus on increased surveillance and evaluation of drug safety warnings in dementia patients to improve the outcomes of the intervention.
- Gabapentin to treat acute alcohol withdrawal in hospitalized patients: A systematic review and meta-analysis. [Review]Drug Alcohol Depend. 2022 Dec 01; 241:109671.DA
- CONCLUSIONS: There is insufficient evidence to support the widespread use of gabapentin to treat inpatients suffering AWS. All studies included in this meta-analysis are retrospective with high risk of confounding. Well-designed, randomized, controlled studies of gabapentin to treat patients with AWS are required.
- Feasibility of a Pragmatic PBPK Modeling Approach: Towards Model-Informed Dosing in Pediatric Clinical Care. [Journal Article]Clin Pharmacokinet. 2022 Dec; 61(12):1705-1717.CP
- CONCLUSIONS: Pragmatic PBPK modeling in pediatrics, based on compound models verified with adult data, is feasible. A thorough understanding of the model assumptions and limitations is required, before model-informed doses can be recommended for clinical use.
- Low-Dose Lorazepam in the Treatment of Catatonia. [Journal Article]Prim Care Companion CNS Disord. 2022 11 03; 24(6)PC
- Pharmacotherapy of alcohol withdrawal syndromes - Recommendations of the Polish Psychiatric Association and the Pharmacotherapy Section of the Polish Society for Addiction Research. [Guideline]Psychiatr Pol. 2022 Jun 30; 56(3):433-452.PP
- Alcohol addiction is one of the most common health problems. Long-term consumption of high doses of ethanol leads to numerous adaptive changes in the central and peripheral nervous systems, most notably a decrease in the activity of inhibitory GABAergic pathways and an increase in the activity of excitatory glutamatergic pathways. Up to half of patients may develop alcohol withdrawal syndrome (AW…
Alcohol addiction is one of the most common health problems. Long-term consumption of high doses of ethanol leads to numerous adaptive changes in the central and peripheral nervous systems, most notably a decrease in the activity of inhibitory GABAergic pathways and an increase in the activity of excitatory glutamatergic pathways. Up to half of patients may develop alcohol withdrawal syndrome (AWS) when they stop drinking alcohol. This article contains the recommendations of the Polish Psychiatric Association and the Pharmacotherapy Section of the Polish Society for Addiction Research for the pharmaco�therapy of AWS. This paper presents the aetiopathogenesis, neurotransmitter and receptor mechanisms, symptoms and diagnostic criteria of AWS, medications used in the treatment of alcohol withdrawal syndromes, management of uncomplicated and complicated alcohol withdrawal syndromes, and discusses the management of special populations. First‑line drugs in the management of AWS are benzodiazepines (BDZ). Most studies have not shown a su�periority of any BDZ in the treatment of AWS. The decision to choose a formulation should be based on its pharmacokinetic properties, comorbidities, and the patient's current condi�tion. The most commonly used BDZs are diazepam, lorazepam, oxazepam, and clorazepate.
- Management of Alcohol Withdrawal Syndrome in Patients with Alcoholic Liver Disease. [Review]J Clin Exp Hepatol. 2022 Nov-Dec; 12(6):1527-1534.JC
- Alcohol withdrawal syndrome (AWS) is a common condition that is seen in treatment-seeking patients with Alcohol use disorder (AUD) and alcoholic liver disease (ALD). AWS, which typically starts within 4-6 h of the last alcohol use, can range from mild symptoms such as insomnia, tremors, and autonomic hyperactivity to more severe symptoms such as seizures and delirium tremens. Clinical Institute W…
Alcohol withdrawal syndrome (AWS) is a common condition that is seen in treatment-seeking patients with Alcohol use disorder (AUD) and alcoholic liver disease (ALD). AWS, which typically starts within 4-6 h of the last alcohol use, can range from mild symptoms such as insomnia, tremors, and autonomic hyperactivity to more severe symptoms such as seizures and delirium tremens. Clinical Institute Withdrawal Assessment Scale-Alcohol Revised (CIWA-Ar) is the most commonly used scale to assess AWS in clinical practice. The presence of moderate withdrawal as indicated by a score of more than 8 is an indication for pharmacotherapy. Lorazepam and oxazepam are preferred agents for the management of AWS in the setting of ALD. In severe ALD, benzodiazepines should be used cautiously with monitoring due to the risk of excessive sedation or precipitating hepatic encephalopathy.
- StatPearls: Sedation Vacation in the ICU [BOOK]StatPearls. StatPearls Publishing: Treasure Island (FL)BOOK
- As the name implies, the intensive care unit (ICU) is where a hospital's sickest patients who require accelerated and concentrated care are admitted. Many of these patients, an estimated 33% of all admissions, are admitted for respiratory failure of one etiology or another and subsequently are intubated and placed on mechanical ventilatory control. Part of the standard of care for intubation is t…
As the name implies, the intensive care unit (ICU) is where a hospital's sickest patients who require accelerated and concentrated care are admitted. Many of these patients, an estimated 33% of all admissions, are admitted for respiratory failure of one etiology or another and subsequently are intubated and placed on mechanical ventilatory control. Part of the standard of care for intubation is to sedate the patient continuously to reduce pain and anxiety; decrease oxygen consumption and the body’s stress response; prevent patient-ventilator desynchrony; reduce adverse neurocognitive impacts such as depression and post-traumatic stress disorder and ventilator-associated events including pneumonia and tracheostomy, and reduce total nursing requirements. The medications used to initiate and maintain sedation within an intensive care unit setting include benzodiazepines such as diazepam, lorazepam, and midazolam; opioid analgesics such as fentanyl, hydromorphone, morphine, remifentanil, propofol, dexmedetomidine, and ketamine; and antipsychotics such as haloperidol, quetiapine, and ziprasidone. No sedative is found to be superior in efficacy or mortality. However, The Society of Critical Care Medicine guidelines state to avoid benzodiazepines due to evidence of longer duration of intubation. The choice of which sedative is best lies in the practitioner's clinical assessment of individual patient scenarios, weighing the risk/benefit profile of the medicine to each patient. Regardless of which sedative agent was utilized, total continuous sedation was found to be associated with an extension of the total length of intubation and increased length of the ICU stay and limited the ability to properly assess the mental status of the patient, increased the risk for delirium, and suppressed brainwave function seen on EEG, linking to increased 6-month mortality. It was assessed that daily, short-term cessation of sedation, a “sedation vacation,” led to improved outcomes in patient care. Sedation vacations were first introduced in 2000 with a study by J.P. Kress et al. that was published in the New England Journal of Medicine and recognized as a medical necessity for standard practice within the ICU to wean patients from mechanical ventilation. The study of spontaneous-awakening trials showed that daily sedation interruptions improved the time to extubation of 64 patients by approximately 2 days which reduced the total admission time to the ICU by 3.5 days. This study was further reinforced by two separate trials, the Awakening and Breathing Controlled Trial in 2008 titled the “wake up and breathe” protocol and the No Sedation in Intensive Care Unit Patients trial in 2010. Both of these supporting trials investigated the impacts of imposing a protocol to evaluate and reduce sedation in a structured format and found that spontaneous-breathing trials along with sedation vacations reduced ventilatory dependent days and ICU admission days when compared to non-structured or no sedation vacation protocols.
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- StatPearls: Florida Controlled Substance Prescribing [BOOK]StatPearls. StatPearls Publishing: Treasure Island (FL)BOOK
- Chronic pain and opioid use and abuse is a significant problem in the United States and in Florida. Over one-quarter of United States citizens suffer from chronic pain. It is among the most common complaints seen in an outpatient clinic and the emergency department. The failure to manage chronic pain, as well as the possible complication of opioid dependence related to treatment, can result…
Chronic pain and opioid use and abuse is a significant problem in the United States and in Florida. Over one-quarter of United States citizens suffer from chronic pain. It is among the most common complaints seen in an outpatient clinic and the emergency department. The failure to manage chronic pain, as well as the possible complication of opioid dependence related to treatment, can result in significant morbidity and mortality. One in five patient complaints in an outpatient clinic is related to pain, with over half of all patients seeing their primary care provider for one pain complaint or another. It is paramount that providers have a firm grasp on the management of patients with chronic pain. As a country, the United States spends well over 100 billion dollars a year on healthcare costs related to pain management and opioid dependence. Pain-related expenses exceed those for the costs of cancer, diabetes, and heart disease combined. How a patient's chronic pain gets managed can have profound and long-lasting effects on a patient's quality of life. The International Association for the Study of Pain defines chronic pain as any pain lasting longer than three months. There are multiple sources of chronic pain. Combination therapy for pain includes both pharmacological therapies and nonpharmacological treatment options. There is a more significant reduction in pain with combination therapy compared to a single treatment alone. Escalation of pharmacological therapy is in a stepwise approach. Comorbid depression and anxiety are widespread in patients with chronic pain. Patients with chronic pain are also at increased risk for suicide. Chronic pain can impact every facet of a patient's life. Thus learning to diagnose and appropriately manage patients experiencing chronic pain is critical. Unfortunately, studies have revealed an inherent lack of education regarding pain management in most professional schools and training programs. Many schools have committed to opioid-related education and training by incorporating the Centers for Disease Control and Prevention guidelines for prescribing opioids for chronic pain into the medical school curriculum. Appropriate opioid prescribing includes prescribing sufficient opioid medication through regular assessment, treatment planning, and monitoring to provide effective pain control while avoiding addiction, abuse, overdose, diversion, and misuse. To be successful, clinicians must understand appropriate opioid prescribing, assessment, the potential for abuse and addiction, and potential psychological problems. Inappropriate opioid prescribing typically involves not prescribing, under prescribing, overprescribing, or continuing to prescribe opioids when they are no longer effective. The American Society of Addiction Medicine describes addiction as a treatable chronic disease that involves environmental pressures, genetics, an individual's life experiences, and interactions among brain circuits. Individuals that become addicted to opioids or other medications often engage in behaviors that become compulsive and result in dangerous consequences. The American Society of Addiction Medicines notes that while the following should not be used as diagnostic criteria due to variability among addicted individuals, they identify five characteristics of addiction: 1. Craving for drug or positive reward. 2. Dysfunctional emotional response. 3. Failure to recognize significant problems affecting behavior and relationships. 4. Inability to consistently abstain. 5. Impairment in control of behavior. Unfortunately, for most health providers, understanding of addiction is often confusing, inaccurate, and inconsistent due to the broad range of perspectives of those dealing with patients suffering from addiction. While a knowledge gap is present among healthcare providers, it is equally prevalent in politicians writing laws and law enforcement attempting to enforce the laws they write. Payers are responsible for the expenses associated with the evaluation and treatment of addiction. Persistent lack of education and the use of obsolete terminology continue to contribute to a societal lack of understanding for effectively dealing with the challenges of addiction. In the past, the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders defined "addiction," "substance abuse," and "substance dependence" separately. The result was provider confusion contributed to the under-treatment of pain. Over time, the manual has eliminated these terms and now uses "substance use disorder," ranging from mild to severe. Unfortunately, there are numerous challenges in pain management, such as both underprescribing and overprescribing opioids. The concerns are particularly prominent in patients with chronic pain and have resulted in patients suffering from inadequately treated pain while at the same time there has been a development of concomitant opioid abuse, addiction, diversion, and overdose. As a result, providers are often negatively influenced and fail to deliver appropriate, effective, and safe opioids to patients with chronic pain. Providers have, in the past, been poorly trained and ill-informed in their opioid prescribing. To make the challenges even worse, chronic pain patients often develop opioid tolerance, significant psychological, behavioral, and emotional problems, including anxiety and depression related to under or overprescribing opioids. Clinicians who prescribe opioids face challenges that involve medical negligence in either failure to provide adequate pain control or risk of licensure or even criminal charges if it is perceived they are involved in drug diversion or misuse. All providers that prescribe opioids need additional education and training to provide the best patient outcomes and avoid the social and legal entanglements associated with over and under prescribing opioids. Prescribers of Controlled Substances In Florida : Physicians (DOs/MDs). Physician Assistants. Podiatrists. Dentists. Optometrists. Advanced Practice Registered Nurses. Veterinarians. Provider Opioid Knowledge Deficit There are substantial knowledge gaps around appropriate and inappropriate opioid prescribing, including deficits in understanding current research, legislation, and appropriate prescribing practices. Providers often have knowledge deficits that include: Understanding of addiction. At-risk opioid addiction populations. Prescription vs. non-prescription opioid addiction. The belief that addiction and dependence on opioids is synonymous. The belief that opioid addiction is a psychologic problem instead related to a chronic painful disease. With a long history of misunderstanding, poor society, provider education, and inconsistent laws, the prescription of opioids has resulted in significant societal challenges that will only resolve with significant education and training. Misuse of Controlled Substances Unfortunately, the misuse of controlled substances resulting in morbidity and mortality is rampant. According to the National Survey on Drug Use and Health,2016, performed by the U.S. Department of Health and Human Services, over 10 million people misuse prescription pain medications, and over 2 million misuse sedatives, stimulants, and tranquilizers each year. The same study found that the most common reason for misuse is for the treatment of physical pain. The Center for Disease Control estimates more than 40,000 people die each year die from an opioid overdose. Controlled Substances There are three common classes of controlled substances commonly misused: opioids, depressants, and stimulants. Opioids Opioids are prescribed for pain control by binding to mu-opioid receptors in the central nervous system reducing pain signals to the brain as well as receptors in the GI tract and respiratory system, and are used to treat pain, diarrhea, and cough. Common Opioids Codeine - One of the most commonly taken opioid medications. It is at the center of the opioid addiction problem in the United States and thus is highly regulated. Its main indication is for pain and cough. FDA-Approved Indication Pain Codeine plays a role in the treatment of mild to moderate pain. Its use is recognized in chronic pain due to ongoing cancer and palliative care. However, the use of codeine to treat other types of chronic pain remains controversial. Chronic pain, defined by the International Association for the Study of Pain, is pain persisting beyond the standard tissue healing time, which is three months. The most prevalent causes of non-cancer chronic pain include back pain, fibromyalgia, osteoarthritis, and headache. Non-FDA Approved Indications Cough Codeine is useful in the treatment of various etiologies producing chronic cough. Also, 46% of patients with chronic cough do not have a distinct etiology despite a proper diagnostic evaluation. Codeine produces a decrease in cough frequency and severity in these patients. However, there is limited literature demonstrating the efficacy of codeine in chronic cough. The dose can vary from 15 mg to 120 mg a day. It is, however, indicated in the management of prolonged cough (in specific populations like lung cancer) usually as 30 mg every 4 to 6 hours as needed. Restless Leg Syndrome Codeine is effective in treating restless leg syndrome when given at night time, especially for those whose symptoms are not relieved by other medications. Persistent Diarrhea (Palliative) Codeine and loperamide are equally effective, and the choice between them has its basis in the assessment of the physician evaluating the small but undoubted addictive potential of codeine versus the higher cost of loperamide, and an individual difference in patient's vulnerability to adverse effects. Fentanyl - Transdermal patch and IV, commonly abused and used in mixture with other drugs. Fentanyl is a synthetic opioid that is 80-100 times stronger than morphine and is often added to heroin to increase its potency. It can cause severe respiratory depression and death, particularly mixed when mixed with other drugs or alcohol. It has a high addiction potential. Hydrocodone - Hydrocodone is a schedule II semi-synthetic opioid medication used to treat pain. Immediate-release (IR) hydrocodone is available as a combination product (combined with acetaminophen, ibuprofen, etc.) and is FDA approved for the management of pain severe enough to require an opioid analgesic and for which alternative (non-opioid) treatments are inadequate. Single-entity hydrocodone is only available in extended-release (ER) formulations. It is FDA approved to treat persistent pain severe enough to require 24-hour, long-term opioid treatment, and for which alternative treatments are inadequate. Hydrocodone is also an antitussive and indicated for cough in adults. Morphine Sulfate - FDA-approved usage of morphine sulfate includes moderate to severe pain that may be acute or chronic. Most commonly used in pain management, morphine provides significant relief to patients afflicted with pain. Clinical situations that benefit significantly by medicating with morphine include managing palliative/end-of-life care, active cancer treatment, and vaso-occlusive pain during sickle cell crisis. Morphine is widely used off-label for almost any condition that causes pain. In the emergency department, morphine is given for musculoskeletal pain, abdominal pain, chest pain, arthritis, and even headaches when patients fail to respond to first and second-line agents. Morphine is rarely used for procedural sedation. However, clinicians will sometimes combine a low dose of morphine with a low dose of benzodiazepine-like lorazepam for small procedures. Oxycodone - An opioid agonist prescription medication. The oxycodone immediate-release formulation is FDA-approved for the management of acute or chronic moderate to severe pain for which other treatments do not suffice, and for which the use of opioid medication is appropriate. The extended-release formulation is FDA-approved for the management of pain severe enough to require continuous (24 hours per day), long-term opioid treatment, and for which there are no alternative options to treat the pain. The oxycodone to morphine dose equivalent ratio is approximately 1 to 1.5 for immediate-release and 1 to 2 for extended-release formulations. Tramadol - Tramadol is an FDA approved medication for pain relief. It has specific indications for moderate to severe pain. It is considered a class IV drug by the FDA. Due to possible abuse and addiction potential, limitations to its use should be for pain that is refractive to other pain medication, such as non-opioid pain medication. There are two forms of tramadol: extended-release and immediate release. The immediate-release is not for use as an "as needed" medication; instead, it is for pain of less than a week duration. For pain lasting more than a week, extended-release is the therapeutic choice — the indication for extended-release is for pain control under 24-hour management or an extended period. Off-label, the drug is useful for premature ejaculation and restless leg syndrome refractory to other medications. For the off-label use of tramadol for premature ejaculation, both sporadic and daily use is effective for the treatment of the condition. Patients indicate a preference for "as needed" therapy for premature ejaculation due to the lack of side effects compared to the daily use of tramadol. Addiction, Dependence, and Tolerance While each of these terms is similar, providers should be aware of the differences. Addiction - the constant need for a drug despite harmful consequences. Pseudoaddiction - constant fear of being in pain, hypervigilance; usually, there is a resolution with pain resolution. Dependence - physical adaptation to a medication where it is necessary for normal function and withdrawal occurs with lack of the medication. Tolerance - lack of expected response to a medication increasing dose to achieve the same pain relief resulting from CNS adaptation to the medication over time.