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1.
Psychopharmacology (Berl) ; 239(10): 3367-3375, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36063207

ABSTRACT

RATIONALE: Mania (or manic episodes) is a common symptom of bipolar disorder and is frequently accompanied by hyperactivity and delusions; given the cost and resources available, there is a paucity of evidence for direct comparison of different drugs. OBJECTIVES: We aimed to provide evidence-based recommendations on the efficacy of overall currently used pharmacological treatments for patients with acute bipolar mania. METHOD: We conducted a systematic review and network meta-analysis (NMA) using a Bayesian network frame. We searched the primary literature databases without language restrictions until Dec 18, 2021, for reports of randomized controlled trials (RCTs) of suspected antimanic drugs used as monotherapy for patients with acute bipolar mania, with the primary outcomes being efficacy (mean difference (MD), standardized mean difference (SMD) in the change of mania score). RESULTS: Eighty-seven studies were included in which 18,724 manic participants (mean age = 34.6 years, with 50.36% males) were allocated at random to one of 25 active medication drug therapies or placebo, resulting in 87 direct comparisons on 192 data points. Tamoxifen (- 22·00 [- 26·00 to - 18·00]) had the best efficacy over the placebo. Meanwhile, risperidone (- 6·60 [- 8·40 to - 4·90]) was substantially more effective than placebo in treating acute mania. Carbamazepine, haloperidol, ziprasidone, cariprazine, olanzapine, quetiapine, aripiprazole, lithium, paliperidone, asenapine, and divalproex were noticeably more effective than placebo. CONCLUSIONS: Overall, tamoxifen appears to be the most effective of the currently known pharmaceutical therapy available to treat acute mania or manic episodes; however, this conclusion is restricted by the scale of RCTs conducted, and risperidone was found to be the most effective medication among antipsychotics. Carbamazepine, haloperidol, ziprasidone, cariprazine, olanzapine, quetiapine, aripiprazole, lithium, paliperidone, asenapine, and divalproex were noticeably effective in treating acute mania or manic episodes.


Subject(s)
Antimanic Agents , Antipsychotic Agents , Adult , Antimanic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Aripiprazole , Benzodiazepines/therapeutic use , Carbamazepine , Dibenzocycloheptenes , Haloperidol/therapeutic use , Humans , Lithium , Mania , Network Meta-Analysis , Olanzapine , Paliperidone Palmitate , Pharmaceutical Preparations , Piperazines , Quetiapine Fumarate , Risperidone/therapeutic use , Tamoxifen , Thiazoles , Valproic Acid/therapeutic use
5.
J Med Internet Res ; 24(9): e35514, 2022 Sep 19.
Article in English | MEDLINE | ID: mdl-36121697

ABSTRACT

BACKGROUND: Long-term dependence on prescribed benzodiazepines is a public health problem. Eliminating Medications Through Patient Ownership of End Results (EMPOWER) is a promising self-management intervention, delivered directly to patients as a printed booklet, that is effective in promoting benzodiazepine reduction and cessation in older adults. EMPOWER has high potential to benefit large health care systems such as the US Veterans Health Administration (VHA), which cares for many veterans who use benzodiazepines for extended periods. OBJECTIVE: We aimed to adapt the original EMPOWER booklet materials for electronic delivery and for use among US military veterans receiving VHA care who were long-term benzodiazepine users. METHODS: We used elements of Analysis, Design, Development, Implementation, and Evaluation, a framework commonly used in the field of instructional design, to guide a qualitative approach to iteratively adapting EMPOWER Electronic Delivery (EMPOWER-ED). We conducted 3 waves of focus groups with the same 2 groups of VHA stakeholders. Stakeholders were VHA-enrolled veterans (n=16) with medical chart evidence of long-term benzodiazepine use and national VHA leaders (n=7) with expertise in setting VHA policy for prescription benzodiazepine use and developing electronically delivered educational tools for veterans. Qualitative data collected from each wave of focus groups were analyzed using template analysis. RESULTS: Themes that emerged from the initial focus groups included veterans' anxiety about self-tapering from benzodiazepines and prior negative experiences attempting to self-taper without support. Participants also provided feedback on the protocol's look and feel, educational content, the tapering protocol, and website functionality; for example, feedback from policy leaders included listing, on the cover page, the most commonly prescribed benzodiazepines to ensure that veterans were aware of medications that qualify for self-taper using the EMPOWER-ED protocol. Both groups of stakeholders identified the importance of having access to supportive resources to help veterans manage sleep and anxiety in the absence of taking benzodiazepines. Both groups also emphasized the importance of ensuring that the self-taper could be personalized and that the taper instructions were clear. The policy leaders emphasized the importance of encouraging veterans to notify their provider of their decision to self-taper to help facilitate provider assistance, if needed, with the taper process and to help prevent medication stockpiling. CONCLUSIONS: EMPOWER-ED is the first direct-to-patient electronically delivered protocol designed to help US military veterans self-taper from long-term benzodiazepine use. We used the Analysis, Design, Development, Implementation, and Evaluation framework to guide the successful adaption of the original EMPOWER booklet for use with this population and for electronic delivery. The next step in this line of research is to evaluate EMPOWER-ED in a randomized controlled trial.


Subject(s)
Benzodiazepines , Veterans , Aged , Benzodiazepines/therapeutic use , Focus Groups , Humans , Ownership , Veterans Health
6.
An Sist Sanit Navar ; 45(2)2022 Aug 17.
Article in English | MEDLINE | ID: mdl-35975325

ABSTRACT

BACKGROUND: There has been a steadily growing trend in prescribing benzodiazepines over last decade. Spain is one of the countries where this class of drugs is most extensively prescribed by primary healthcare physicians. The aim of this study is to identify factors that might be acting as barriers and enablers for benzodiazepine (de)prescription from patient and professional perspectives. METHODS: Qualitative study through semi-structured interviews with medical practitioners (n=17) and patients (n=27), and a nominal group with medical practitioners (n=19). Interviews were audio-recorded, transcribed and analyzed using thematic analysis. RESULTS: The analysis revealed key themes and was organized around barriers and enablers connected to three interrelated dimen-sions: the social and community context of prescription; the structure, organization and/or management of the health system, and the doctor-patient relationship. The excessive workload of professionals was widely cited as influencing over-prescription. (De)prescription of benzodiazepine was facilitated by encouraging the social prescription of health assets or developing strategies to therapeutic alliance processes and better doctor-patient communication. CONCLUSION: Our findings suggest that there is a role for the salutogenic approach and the health asset model in the development of a more person-centred clinical care. This study considers the importance of encouraging the use of non-pharmacological methods and techniques in the health system and promoting the creation of multidisciplinary teams, therapeutic alliance processes and better doctor-patient communication by giving professionals training in psychosocial skills.


Subject(s)
Attitude of Health Personnel , Benzodiazepines , Benzodiazepines/therapeutic use , Humans , Physician-Patient Relations , Prescriptions , Qualitative Research
7.
Int J Mol Sci ; 23(15)2022 Jul 27.
Article in English | MEDLINE | ID: mdl-35955425

ABSTRACT

Antipsychotics used to treat schizophrenia can cause drug-induced liver injury (DILI), according to the Roussel Uclaf Causality Assessment Method. The role of oxidative stress in triggering injury in these DILI cases is unknown. We repeatedly administrated two second-generation antipsychotics, aripiprazole and olanzapine, at laboratory alert levels to study underlying mechanisms in stress prevention upon acute oxidative stress. The drugs were administered continuously for up to 8 weeks. For this, hepatoma Fao cells, which are suitable for metabolic studies, were used, as the primary hepatocytes survive in the culture only for about 1 week. Four stress responses-the oxidative stress response, the DNA damage response and the unfolded protein responses in the endoplasmic reticulum and mitochondria-were examined in H2O2-treated cells by antioxidant enzyme activity measurements, gene expression and protein quantification. Oxidant conditions increased the activity of antioxidant enzymes and upregulated genes and proteins associated with oxidative stress response in aripiprazole-treated cells. While the genes associated with DNA damage response, Gadd45 and p21, were upregulated in both aripiprazole- and olanzapine-treated cells, only aripiprazole treatment was associated with upregulation in response to even more H2O2, which also coincided with better survival. Endoplasmic reticulum stress-induced Chop was also upregulated; however, neither endoplasmic reticulum nor mitochondrial unfolded protein response was activated. We conclude that only aripiprazole, but not olanzapine, protects liver cells against oxidative stress. This finding could be relevant for schizophrenia patients with high-oxidative-stress-risk lifestyles and needs to be validated in vivo.


Subject(s)
Antipsychotic Agents , Chemical and Drug Induced Liver Injury , Antioxidants/pharmacology , Antipsychotic Agents/pharmacology , Antipsychotic Agents/therapeutic use , Aripiprazole/pharmacology , Benzodiazepines/pharmacology , Benzodiazepines/therapeutic use , Chemical and Drug Induced Liver Injury/drug therapy , Hepatocytes , Humans , Hydrogen Peroxide , Olanzapine/adverse effects , Oxidative Stress
8.
J Psychosoc Nurs Ment Health Serv ; 60(9): 6-9, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36044745

ABSTRACT

Pediatric anxiety disorders (PADs) occur in up to 20% of youth and can cause impairment across the lifespan. Coronavirus disease 2019 (COVID-19) added unique pressures on those with PADs, as children and adolescents endured the longest pandemic restrictions, stymieing their ability to develop socially, emotionally, and cognitively. Although first-line treatment for PADs is psychotherapy, those with severe anxiety symptoms will require pharmacological interventions. Selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor (SNRI) medications are effective in treating PADs, yet only duloxetine (a SNRI) is approved by the U.S. Food and Drug Administration for children aged >7 years with generalized anxiety disorder. Treatment of children and adolescents with benzodiazepines for PADs presents unique challenges with potential paradoxical reactions. Caution must be observed as well due to risk for misuse related to long-term use of benzodiazepines with PADs. [Journal of Psychosocial Nursing and Mental Health Services, 60(9), 6-9.].


Subject(s)
COVID-19 , Serotonin and Noradrenaline Reuptake Inhibitors , Adolescent , Anxiety Disorders/drug therapy , Benzodiazepines/therapeutic use , Child , Humans , Norepinephrine/therapeutic use , Serotonin Uptake Inhibitors/therapeutic use , Serotonin and Noradrenaline Reuptake Inhibitors/therapeutic use
9.
Arq Neuropsiquiatr ; 80(5 Suppl 1): 193-203, 2022 05.
Article in English | MEDLINE | ID: mdl-35976303

ABSTRACT

Status epilepticus (SE) is a frequent neurological emergency associated with high morbidity and mortality. According to the new ILAE 2015 definition, SE results either from the failure of the mechanisms responsible for seizure termination or initiation, leading to abnormally prolonged seizures. The definition has different time points for convulsive, focal and absence SE. Time is brain. There are changes in synaptic receptors leading to a more proconvulsant state and increased risk of brain lesion and sequelae with long duration. Management of SE must include three pillars: stop seizures, stabilize patients to avoid secondary lesions and treat underlying causes. Convulsive SE is defined after 5 minutes and is a major emergency. Benzodiazepines are the initial treatment, and should be given fast and an adequate dose. Phenytoin/fosphenytoin, levetiracetam and valproic acid are evidence choices for second line treatment. If SE persists, anesthetic drugs are probably the best option for third line treatment, despite lack of evidence. Midazolam is usually the best initial choice and barbiturates should be considered for refractory cases. Nonconvulsive status epilepticus has a similar initial approach, with benzodiazepines and second line intravenous (IV) agents, but after that, aggressiveness should be balanced considering risk of lesion due to seizures and medical complications caused by aggressive treatment. Usually, the best approach is the use of sequential IV antiepileptic drugs (oral/tube are options if IV options are not available). EEG monitoring is crucial for diagnosis of nonconvulsive SE, after initial control of convulsive SE and treatment control. Institutional protocols are advised to improve care.


Subject(s)
Status Epilepticus , Anticonvulsants/therapeutic use , Benzodiazepines/therapeutic use , Humans , Levetiracetam/therapeutic use , Seizures/complications , Status Epilepticus/diagnosis , Status Epilepticus/drug therapy
10.
Expert Opin Drug Metab Toxicol ; 18(7-8): 507-518, 2022.
Article in English | MEDLINE | ID: mdl-35979611

ABSTRACT

INTRODUCTION: The effects of antipsychotic drugs are dose-dependent, which is particularly true for their efficacy, each antipsychotic having a specific dose-response curve. This may justify individualizing doses for these agents. AREAS COVERED: We review the pharmacokinetic profiles of seven oral antipsychotics: haloperidol, risperidone, olanzapine, clozapine, quetiapine, ziprasidone, and aripiprazole. Their main indications are psychotic and affective disorders. They are prescribed in a very large population which may have comorbidities. Hence, we analyze the impact of the latter on the pharmacokinetic profiles of these antipsychotics, focusing on renal and hepatic impairment. Reviews and clinical trials were discussed based on a systematic literature search (PubMed) ranging from 1995 to 2022. EXPERT OPINION: Factors liable to impact antipsychotic dosage are numerous and their subsequent effects often hard to predict, due to multilevel interactions and compensatory phenomena. In clinical practice, physicians must be aware of these potential effects, but base their decisions on monitoring antipsychotic plasma levels.


Subject(s)
Antipsychotic Agents , Clozapine , Benzodiazepines/therapeutic use , Humans , Olanzapine , Quetiapine Fumarate , Risperidone/therapeutic use
11.
J Clin Psychiatry ; 83(3)2022 Mar 14.
Article in English | MEDLINE | ID: mdl-36036650

ABSTRACT

Objective: Our objective was to characterize benzodiazepine prescribing changes among veterans with posttraumatic stress disorder (PTSD) and inform efforts to deimplement low-value prescribing practices.Methods: This retrospective observational study used national Veterans Health Administration (VHA) administrative databases to examine annual period prevalence and incidence of benzodiazepine prescribing from 2009 through 2019 in veterans with PTSD. International Classification of Diseases (ICD-9/10) codes were used to identify PTSD. Temporal trends in discontinuation rates, incidence rates, and prevalent prescribing among patients newly engaged in PTSD care were measured.Results: Benzodiazepine prevalence in veterans with PTSD declined from 31.3% in 2009 to 10.7% in 2019, and incidence decreased from 11.4% to 2.9%, along with a 30% decrease in daily doses. Increasing discontinuation rates accounted for 21.0% of the decline in prevalence, while decreasing incidence among existing patients accounted for 36.8%, and decreased prevalence among new PTSD cohort entrants accounted for 42.2%. Women received benzodiazepines more commonly than men (odds ratio [OR] = 1.67; 95% CI, 1.64-1.70). The proportion of older adults increased over time among both existing (2009: 14.5%; 2019: 46.5%) and new (2009: 8.6%; 2019: 24.3%) benzodiazepine recipients.Conclusions: Benzodiazepine prescribing in VHA among veterans with PTSD showed changes driven by decreases in prevalence among new PTSD cohort entrants, with smaller changes in discontinuation and decreased incidence among existing patients. Educational initiatives may have curtailed benzodiazepine prescribing through promotion of effective alternative treatment options and supporting discontinuation through various tapering strategies. These initiatives offer resources and lessons to other health care systems to deimplement inappropriate benzodiazepine prescribing and other potentially harmful practices through patient-centered approaches that promote viable treatment alternatives.


Subject(s)
Stress Disorders, Post-Traumatic , Veterans , Aged , Benzodiazepines/therapeutic use , Female , Humans , Male , Stress Disorders, Post-Traumatic/drug therapy , Stress Disorders, Post-Traumatic/epidemiology , United States/epidemiology , United States Department of Veterans Affairs , Veterans Health
12.
Pediatr Emerg Care ; 38(9): e1545-e1551, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35947072

ABSTRACT

OBJECTIVES: In the present study, we aimed to determine the changes in the administration rate of benzodiazepines for pediatric patients with suspected nonconvulsive status epilepticus (NCSE) before and after the introduction of simplified electroencephalography (sEEG) in the emergency department. METHODS: This retrospective cohort study included patients who were younger than 18 years and were admitted to the emergency department from August 1, 2009, to July 31, 2017, with altered level of consciousness and nonpurposeful movement of eyes or extremities after the cessation of convulsive status epilepticus. Patients with apparent persistent convulsions, those who were fully conscious on arrival, and those who were transferred from another hospital were excluded. The patients were categorized into pre and post groups based on the introduction of sEEG, and benzodiazepine administration was compared between the 2 groups. RESULTS: During the study period, 464 patients with status epilepticus visited our emergency department and 69 and 93 patients fulfilling the study criteria were categorized into the pre and post groups, respectively. There were no significant differences in patient background characteristics between the 2 groups. Simplified electroencephalography was recorded in 52 patients in the post group. Benzodiazepines were administered in 44 of 69 patients (63.8%) in the pre group and 44 of 93 (47.3%) in the post group, and the benzodiazepine administration rate was significantly decreased after the introduction of sEEG ( P = 0.04). The hospitalization rate was significantly lower in the post group, but there were no significant differences in the rates of intensive care unit admission, reconvulsion after discharge, and final diagnoses between the 2 groups. CONCLUSIONS: Simplified electroencephalography might aid in determining the need for anticonvulsant treatment for suspected NCSE in pediatric patients. Albeit not a definitive diagnostic tool, sEEG might be a reliable choice in the evaluation of pediatric patients with suspected NCSE.


Subject(s)
Benzodiazepines , Status Epilepticus , Benzodiazepines/therapeutic use , Child , Electroencephalography , Humans , Retrospective Studies , Seizures , Status Epilepticus/diagnosis , Status Epilepticus/drug therapy
13.
Sci Rep ; 12(1): 14447, 2022 Aug 24.
Article in English | MEDLINE | ID: mdl-36002562

ABSTRACT

Severe delirium is associated with an increased risk of mortality, institutionalization, and length of stay. Few studies have examined differences in delirium severity between different populations of critically ill patients. The objective of the study was to compare delirium severity and the presence of the four core features between adults in the surgical intensive care unit (SICU) and medical intensive care unit (MICU) while controlling for variables known to be associated with delirium. This is a secondary analysis of two parallel randomized multi-center trials conducted from March 2009 to January 2015 at 3 Indianapolis hospitals. A total of 474 adults with delirium were included in the analysis. Subjects were randomized in a 1:1 ratio in random blocks of 4 by a computer program. Patients were randomized to either haloperidol prescribing or de-prescribing regimen vs usual care. Delirium severity was assessed daily or twice-daily using the CAM-ICU-7 beginning after 24 h of ICU admission and until discharge from the hospital, death, or 30 days after enrollment. Secondary outcomes included hospital length of stay, hospital and 30-day mortality, and delirium-related adverse events. These outcomes were compared between SICU and MICU settings for this secondary analysis. Out of 474 patients, 237 were randomized to intervention. At study enrollment, the overall cohort had a mean age of 59 (SD 16) years old, was 54% female, 44% African-American, and 81% were mechanically ventilated upon enrollment. MICU participants were significantly older and severely ill with a higher premorbid cognitive and physical dysfunction burden. In univariate analysis, SICU participants had significantly higher mean total CAM-ICU-7 scores, corresponding to delirium severity, (4.15 (2.20) vs 3.60 (2.32), p = 0.02), and a lower mean RASS score (- 1.79 (1.28) vs - 1.53 (1.27), p < 0.001) compared to MICU participants. Following adjustment for benzodiazepines and opioids, delirium severity did not significantly differ between groups. The presence of Feature 3, altered level of consciousness, was significantly associated with the SICU participants, identifying as Black, premorbid functional impairment, benzodiazepines, opioids, and dexmedetomidine. In this secondary analysis examining differences in delirium severity between MICU and SICU participants, we did not identify a difference between participant populations following adjustment for administered benzodiazepines and opioids. We did identify that an altered level of consciousness, core feature 3 of delirium, was associated with SICU setting, identifying as Black, activities of daily living, benzodiazepines and opioid medications. These results suggest that sedation practice patterns play a bigger role in delirium severity than the underlying physiologic insult, and expression of core features of delirium may vary based on individual factors.Trial registration CT#: NCT00842608.


Subject(s)
Delirium , Activities of Daily Living , Adolescent , Adult , Analgesics, Opioid/therapeutic use , Benzodiazepines/therapeutic use , Consciousness Disorders/complications , Critical Care , Delirium/drug therapy , Delirium/etiology , Female , Humans , Intensive Care Units , Male , Middle Aged
14.
Epilepsy Res ; 185: 106996, 2022 09.
Article in English | MEDLINE | ID: mdl-35963151

ABSTRACT

PURPOSE: Pharmaceutical grade cannabidiol (CBD) is one of the newest anti-seizure medications for refractory epilepsy, and the effects of CBD on EEG have not been fully described. METHODS: Patients enrolled in a CBD expanded access study had EEGs prior to and 12 weeks after initiation of CBD treatment for their refractory epilepsy. In addition to evaluating the clinical EEG reports, a nonbiased quantitative EEG (qEEG) analysis of background EEG was performed to determine whether consistent changes occur in the EEG in response to administration of CBD. RESULTS: No significant qualitative changes were seen, nor changes in quantitative markers of EEG amplitude (RMS amplitude, standard deviation of the amplitude, skewness, or kurtosis), frequency (relative delta, theta, or alpha power), Spearman correlation, or coherence between brain regions. However, relative beta power and 1/f slope, a measure of signal noise increased with the addition of CBD. When patients were separated into responders and nonresponders based on seizure reduction with CBD, responders also had decreased Spearman correlation between the frontopolar and occipital regions after addition of CBD, suggesting that responders may have quantitatively improved EEG background organization after CBD initiation. The differences in beta and 1/f slope were also seen more robustly in CBD responders compared with nonresponders after CBD initiation. These differences disappeared when analyzing only patients not taking benzodiazepines, suggesting that the effect of CBD on seizures was related to the ability of the brain to further increase beta in response to CBD in patients already taking benzodiazepines. We noted that even before initiation of CBD, 1/f slope was also significantly different in responders compared to nonresponders. Therefore, to explore the baseline EEG in responders and nonresponders, we utilized a variable selection procedure to identify baseline EEG features that could predict whether a patient's seizures would improve with CBD. In the optimal multivariable logistic model, baseline coherence, Spearman correlation, and patient sex jointly predicted whether a patient in this cohort would respond to CBD (defined as a seizure reduction of 40% or greater) with 74% accuracy. This model performed less well on a data set of reduced duration and variability, highlighting the importance of real-world testing of any clinically relevant model. CONCLUSION: These results suggest that there are subtle changes in certain metrics detected by qEEG even at baseline that may not be perceived during qualitative EEG analysis and that could be used in the future as a biomarker to predict a patient's clinical response to CBD administration. Development of such a predictive EEG biomarker, especially before the initiation of a medication trial, could reduce unnecessary ASM exposure and improve outcomes for patients with epilepsy facing new medication selection.


Subject(s)
Cannabidiol , Drug Resistant Epilepsy , Anticonvulsants/pharmacology , Benzodiazepines/therapeutic use , Biomarkers , Cannabidiol/therapeutic use , Drug Resistant Epilepsy/drug therapy , Electroencephalography , Humans
15.
Epilepsia ; 63 Suppl 1: S34-S44, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35999174

ABSTRACT

The primary goal of treatment for seizure clusters is cessation of the cluster to avoid progression to more severe conditions, such as prolonged seizures and status epilepticus. Rescue therapies are key components of treatment plans for patients with seizure clusters. Three rescue therapies are approved in the United States for the treatment of seizure clusters: diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray. This review characterizes the pharmacological function of rescue therapies for seizure clusters, as well as describing γ-aminobutyric acid A (GABAA ) receptor functions. GABAA receptors are heteropentamers, consisting primarily of α1-6, ß1-3, γ2, and δ subunits in the central nervous system. These subunits can traffic to and from the membrane to regulate membrane potential. Benzodiazepines, such as diazepam and midazolam, are positive allosteric modulators of GABAA receptors, the activation of which leads to an increase in intracellular chloride, hyperpolarization of the cell membrane, and a reduction in excitation. GABAA receptor subunit mutations, dysregulation of trafficking, and degradation are associated with epilepsy. Although benzodiazepines are effective GABAA receptor modulators, individual formulations have unique profiles in practice. Diazepam rectal gel is an effective rescue therapy for seizure clusters; however, adults and adolescents may have social reservations regarding its administration. Intranasal delivery of midazolam or diazepam is a promising alternative to rectal administration because these formulations offer easy, socially acceptable administration and exhibit a rapid onset. Off-label benzodiazepines, such as orally disintegrating lorazepam and intranasal use of an intravenous formulation of midazolam via nasal atomizer, are less well characterized regarding bioavailability and tolerability compared with approved agents.


Subject(s)
Epilepsy, Generalized , Status Epilepticus , Administration, Intranasal , Adolescent , Adult , Anticonvulsants/therapeutic use , Benzodiazepines/therapeutic use , Diazepam/pharmacology , Diazepam/therapeutic use , Epilepsy, Generalized/drug therapy , Humans , Midazolam/therapeutic use , Nasal Sprays , Receptors, GABA-A , Seizures/drug therapy , Status Epilepticus/drug therapy , gamma-Aminobutyric Acid/therapeutic use
16.
Am Fam Physician ; 106(2): 157-164, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35977134

ABSTRACT

Generalized anxiety disorder (GAD) and panic disorder (PD) are common mental health conditions in adults that are often seen in primary care. Although there is insufficient evidence to support universal screening for PD and GAD, evaluation should be considered in patients who express recurrent, pervasive worry or present with somatic symptoms not attributed to underlying medical conditions. The GAD-7 and Patient Health Questionnaire for PD are validated screening tools that can aid in diagnosis and assessment. Anxiety disorders often present with substance use disorders, which should be treated concurrently. Effective therapies for PD and GAD include cognitive behavior therapy and anti-depressants, including selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Benzodiazepines are not recommended for first-line therapy or long-term use because of adverse reactions, risk of dependence, and higher mortality. No consistent evidence currently supports a specific prevention strategy for PD or GAD, but exercise may be beneficial.


Subject(s)
Cognitive Behavioral Therapy , Panic Disorder , Adult , Anxiety Disorders/diagnosis , Anxiety Disorders/therapy , Benzodiazepines/therapeutic use , Humans , Panic Disorder/diagnosis , Panic Disorder/therapy , Serotonin Uptake Inhibitors/therapeutic use
17.
Pharmacopsychiatry ; 55(5): 233-245, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35777418

ABSTRACT

Early-onset schizophrenia (EOS) - onset before age 18 - is linked with great disease burden and disability. Decision-making for EOS pharmacological treatment may be challenging due to conflicting information from evidence and guidelines and unidentified care needs may remain unmet.We searched for systematic reviews, meta-analyses and umbrella reviews of EOS pharmacological treatment published in PubMed over the past 10 years and selected five clinical guidelines from Europe, North-America and Australia. Based on predefined outcomes, we critically compared the evidence supporting EOS-approved drugs in Europe and/or North-America with guidelines recommendations. We also evaluated the coverage of these outcomes to identify unmet needs.One systematic review, nine meta-analyses and two umbrella reviews (k=203 trials, N=81,289 participants, including duplicated samples across selected articles) were retrieved. Evidence supported the efficacy of aripiprazole, clozapine, haloperidol, lurasidone, molindone, olanzapine, quetiapine, risperidone and paliperidone in EOS, all of which obtained approval for EOS either in Europe and/or in North-America. Cognition, functioning and quality of life, suicidal behaviour and mortality and services utilisation and cost-effectiveness were poorly covered/uncovered.Among the antipsychotics approved for EOS, aripiprazole, lurasidone, molindone, risperidone, paliperidone and quetiapine emerged as efficacious and comparably safe options. Olanzapine is known for a high risk of weight gain and haloperidol for extrapyramidal side-effects. Treatment-resistant patients should be offered clozapine. Future long-term trials looking at cognition, functioning, quality of life, suicidal behaviour, mortality, services utilisation and cost-effectiveness are warranted. Closer multi-agency collaboration may bridge the gap between evidence, guidelines and approved drugs.


Subject(s)
Antipsychotic Agents , Clozapine , Schizophrenia , Adolescent , Antipsychotic Agents/therapeutic use , Aripiprazole/therapeutic use , Benzodiazepines/therapeutic use , Clozapine/therapeutic use , Haloperidol/therapeutic use , Humans , Lurasidone Hydrochloride/therapeutic use , Molindone/therapeutic use , Olanzapine , Paliperidone Palmitate/therapeutic use , Quality of Life , Quetiapine Fumarate/therapeutic use , Risperidone/adverse effects , Schizophrenia/drug therapy , Systematic Reviews as Topic
18.
Psychogeriatrics ; 22(5): 718-727, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35810468

ABSTRACT

BACKGROUND: We aimed to investigate factors associated with concomitant laxative use among elderly patients with schizophrenia, discharged on second-generation antipsychotics (SGAs), from two large public psychiatric hospitals in Taiwan. METHODS: Elderly patients with schizophrenia who were discharged between 2006 and 2019 and received SGA monotherapy at discharge were included in the analysis. Multivariate logistic regression was used to identify factors associated with regular laxative use at discharge. The Cochrane-Armitage trend test was used to evaluate whether significant time trends existed for rates of laxative use at discharge. RESULTS: A total of 2591 elderly patients with schizophrenia were discharged during the study period, and 1727 of 2591 patients who met the inclusion criteria were included for analysis. Of these 1727 patients, 732 (42.4%) also received concomitant laxatives. Female gender, mood stabiliser use and concomitant diabetes mellitus were found to be associated with increased laxative use. Among SGAs, clozapine was associated with the highest rate of laxative use, followed by zotepine, quetiapine, olanzapine and risperidone. Additionally, risperidone, amisulpride, aripiprazole, paliperidone and sulpiride were associated with comparable rates of laxative use. Laxative use rates grew over time from 30.8% in 2006 to 46.6% in 2019 (z = 4.83, P < 0.001). CONCLUSIONS: Laxative use is common in elderly schizophrenia patients treated with SGAs. In cases of clinically significant constipation, switching to an SGA with a lower risk for constipation, or discontinuing the use of mood stabilisers should be considered, if clinically feasible.


Subject(s)
Antipsychotic Agents , Schizophrenia , Aged , Antipsychotic Agents/adverse effects , Benzodiazepines/therapeutic use , Constipation/chemically induced , Constipation/drug therapy , Constipation/epidemiology , Female , Humans , Laxatives/therapeutic use , Piperazines/adverse effects , Quetiapine Fumarate/therapeutic use , Risperidone , Schizophrenia/drug therapy , Thiazoles/adverse effects
20.
Int J Mol Sci ; 23(13)2022 Jun 28.
Article in English | MEDLINE | ID: mdl-35806181

ABSTRACT

Altered protein synthesis has been implicated in the pathophysiology of several neuropsychiatric disorders, particularly schizophrenia. Ribosomes are the machinery responsible for protein synthesis. However, there remains little information on whether current psychotropic drugs affect ribosomes and contribute to their therapeutic effects. We treated human neuronal-like (NT2-N) cells with amisulpride (10 µM), aripiprazole (0.1 µM), clozapine (10 µM), lamotrigine (50 µM), lithium (2.5 mM), quetiapine (50 µM), risperidone (0.1 µM), valproate (0.5 mM) or vehicle control for 24 h. Transcriptomic and gene set enrichment analysis (GSEA) identified that the ribosomal pathway was altered by these drugs. We found that three of the eight drugs tested significantly decreased ribosomal gene expression, whilst one increased it. Most changes were observed in the components of cytosolic ribosomes and not mitochondrial ribosomes. Protein synthesis assays revealed that aripiprazole, clozapine and lithium all decreased protein synthesis. Several currently prescribed psychotropic drugs seem to impact ribosomal gene expression and protein synthesis. This suggests the possibility of using protein synthesis inhibitors as novel therapeutic agents for neuropsychiatric disorders.


Subject(s)
Antipsychotic Agents , Clozapine , Antipsychotic Agents/pharmacology , Antipsychotic Agents/therapeutic use , Aripiprazole , Benzodiazepines/therapeutic use , Clozapine/therapeutic use , Humans , Lithium , Olanzapine , Psychotropic Drugs/pharmacology , Psychotropic Drugs/therapeutic use , Quetiapine Fumarate , Ribosomes
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