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Journal of the Academy of... 2024Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available... (Review)
Review
Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies.
Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.
Topics: Humans; Administration, Intravenous; Psychomotor Agitation; Aggression; Antipsychotic Agents; Prospective Studies
PubMed: 38309683
DOI: 10.1016/j.jaclp.2024.01.004 -
The Primary Care Companion For CNS... Jan 2024The prompt effective treatment of acute agitation among patients with schizophrenia or bipolar disorder can alleviate distressing symptoms for the patient and decrease... (Review)
Review
The prompt effective treatment of acute agitation among patients with schizophrenia or bipolar disorder can alleviate distressing symptoms for the patient and decrease the risk of escalation to aggression and the potential for serious harm to the patient, health care providers, and others. A commonly used approach for the management of acute agitation has been the intramuscular administration of antipsychotic medications and/or benzodiazepines. However, US Food and Drug Administration-approved treatments with alternative routes of delivery now include inhaled loxapine powder and, more recently, dexmedetomidine sublingual film. Two formulations of intranasal olanzapine for acute agitation are in development. Intranasal formulations offer the potential for favorable pharmacokinetics and onset of action combined with ease of delivery obviating the need for injections and are thus consistent with patient-centered factors such as preference and self-administration. In this review, alternative methods of medication delivery are discussed, with an emphasis on the potential for intranasal administration to treat acute agitation in adult patients with schizophrenia or bipolar disorder. .
Topics: Adult; Humans; Schizophrenia; Antipsychotic Agents; Bipolar Disorder; Psychomotor Agitation; Loxapine
PubMed: 38301034
DOI: 10.4088/PCC.23nr03596 -
Life (Basel, Switzerland) Dec 2023This meta-analysis aimed to assess the association between mild traumatic brain injury (mTBI) and the risk of developing Parkinsonism. A systematic literature review was... (Review)
Review
This meta-analysis aimed to assess the association between mild traumatic brain injury (mTBI) and the risk of developing Parkinsonism. A systematic literature review was conducted using PubMed, Embase, and Cochrane Library databases. Studies were eligible if they reported on the association between MTBI and Parkinsonism. Pooled odds ratios (ORs) were calculated using a random-effects model. Publication bias was assessed using Egger's and Begg's tests. A total of 18 studies were included in this meta-analysis, with 1,484,752 participants. The overall OR for Parkinsonism in individuals with a history of mTBI was 1.637 (95% CI, 1.203-2.230; = 0.01), indicating a significant association. The OR for Parkinson's disease (PD) specifically was 1.717 (95% CI, 1.206-2.447; = 0.01). However, insufficient data on tics and akathisia limited a meta-analysis. There was no evidence of publication bias according to Egger's ( = 0.8107) and Begg's ( = 0.4717) tests. This meta-analysis provides evidence that mTBI is a significant risk factor for Parkinsonism, particularly PD. However, the findings should be interpreted with caution due to the heterogeneity among the studies included and the study's limitations. Further research is needed to confirm these findings and to investigate the underlying mechanisms of the mTBI-Parkinsonism association.
PubMed: 38255648
DOI: 10.3390/life14010032 -
International Journal of Environmental... Dec 2023Interest in eccentric exercises has increased over the last decades due to its efficiency in achieving moderate-high intensity muscular work with reduced metabolic...
Interest in eccentric exercises has increased over the last decades due to its efficiency in achieving moderate-high intensity muscular work with reduced metabolic demands. However, individualizing eccentric exercises in rehabilitation contexts remains challenging, as concentric exercises mainly rely on cardiovascular parameters. To overcome this, perceived exertion could serve as an individualization tool, but the knowledge about cardiovascular responses to eccentric cycling based on perceived exertion are still scarce. For this purpose, the cardiorespiratory parameters of 26 participants were assessed during two 5 min bouts of concentric cycling at 30 and 60 rpm and two bouts of eccentric cycling at 15 and 30 rpm matched for rating of perceived exertion. With this method, we hypothesized higher exercise efficiency during eccentric cycling for a same perceived exertion. The results revealed significantly elevated heart rate and cardiac index at higher pedalling rates during concentric ( < 0.001), but not during eccentric cycling ( ≈ 1). Exercise efficiency was higher during concentric cycling (64%), decreasing with pedalling rate, while eccentric cycling exhibited increased work rates (82%), and increased by over 100% with higher pedalling rate. Hence, eccentric cycling, with lower cardiorespiratory work for the same perceived exertion, facilitates higher work rates in deconditioned populations. However, further studies are needed for effective individualization.
Topics: Humans; Physical Exertion; Cardiovascular System; Exercise; Exercise Therapy; Bicycling; Psychomotor Agitation
PubMed: 38248524
DOI: 10.3390/ijerph21010059 -
Clinical Psychopharmacology and... Feb 2024: Recent evidence suggests that oxidative stress contributes to the pathophysiology of schizophrenia. This study aimed to compare thiol-disulphide homeostasis in acute...
OBJECTIVE
: Recent evidence suggests that oxidative stress contributes to the pathophysiology of schizophrenia. This study aimed to compare thiol-disulphide homeostasis in acute and stable phases of schizophrenia for the first time.
METHODS
: Among the patients with schizophrenia, 61 in the acute-phase and 61 in the stable phase of their illness were enrolled in the study. Native thiol (NT), total thiol (TT), disulphide (SS), disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol for thiol-disulphide homeostasis were compared between the groups. The Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive/Negative Symptoms (SAPS/SANS), Clinical Global Impression-Severity Scale (CGI-S), Barnes Akathisia Rating Scale, and Simpson-Angus Scale were used to assess symptoms.
RESULTS
: After controlling for age, sex, body mass index, and smoking status there were significant differences in NT, TT, SS/NT, SS/TT, and NT/TT, but not SS. Thiol/disulphide homeostasis has shifted in favour of the oxidative side in patients with acute-phase compared to that in stable schizophrenia. BPRS, SAPS, and CGI-S scores were significantly correlated with all six thiol-disulphide parameters, but not SANS, when controlling for age and sex. Significant receiver operating characteristic (ROC) curves were obtained for all thiol-disulphide homeostasis parameters. Discriminant analysis was found to be statistically significant in discriminating between groups.
CONCLUSION
: These results show that oxidative status increases thiol-disulphide homeostasis in patients with acute-phase schizophrenia compared to those with stable schizophrenia. These findings suggest that thiol-disulphide parameters can be used as biomarkers for the acute exacerbation of schizophrenia.
PubMed: 38247420
DOI: 10.9758/cpn.23.1084 -
Frontiers in Pharmacology 2023The aim of our study was to evaluate the efficacy of cariprazine augmentation of clozapine in treatment-resistant schizophrenia in a retrospective chart review. Among...
The aim of our study was to evaluate the efficacy of cariprazine augmentation of clozapine in treatment-resistant schizophrenia in a retrospective chart review. Among 916 medical records of schizophrenia patients, we identified 12 individuals treated with a combination of those drugs for a duration of 3-60 weeks [median 32 (10-40)]. Clinical Global Impression-Improvement (CGI-I) scores were used to measure the treatment response between the introduction of cariprazine augmentation of clozapine and the last point of observation. The majority of the patients presented treatment response (9/12 patients, 75%) after 4-16 weeks of therapy [median 6 (4-12)]. Treatment was associated with the decrease in positive, negative, affective, and anxiety symptom severity, as well as improvement of patient global functioning. One patient discontinued the treatment due to side effects (akathisia), and two patients halted the therapy due to the exacerbation of psychotic symptoms. Our study presents a thorough clinical description of the largest number of treatment-resistant schizophrenia patients medicated using cariprazine augmentation of clozapine in a "real-world" setting. Our results suggest that the use of this combination may lead to the improvement in a broad range of symptoms of patients with this condition.
PubMed: 38239199
DOI: 10.3389/fphar.2023.1321112 -
The Journal of Clinical Psychiatry Jan 2024To determine if iloperidone, a second-generation antipsychotic, reduces symptoms of bipolar mania. This phase 3, randomized, double-blind, placebo-controlled study was... (Randomized Controlled Trial)
Randomized Controlled Trial
To determine if iloperidone, a second-generation antipsychotic, reduces symptoms of bipolar mania. This phase 3, randomized, double-blind, placebo-controlled study was conducted in adults with bipolar mania at 27 US and international sites between April 2021 and September 2022. Participants were randomized 1:1 to iloperidone (up to 24 mg/d given twice daily) or placebo for 4 weeks. The primary efficacy endpoint was change from baseline to week 4 in Young Mania Rating Scale (YMRS) total score versus placebo. Secondary efficacy endpoints included change from baseline in the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales. Altogether, 414 participants were randomized and administered at least 1 dose of study medication (iloperidone, n = 206; placebo, n = 208). Overall, 139 (67.1%) iloperidone patients and 153 (72.9%) placebo patients completed the study. Iloperidone demonstrated significant improvement versus placebo at week 4 for the primary and secondary endpoints. Differences in the least-squares mean (95% CI; value) of change from baseline for YMRS total scores were -4.0 (-5.70 to -2.25; adjusted = .000008). The most encountered adverse events with iloperidone were tachycardia, dizziness, dry mouth, alanine aminotransferase increased, nasal congestion, increased weight, and somnolence. The incidence of akathisia and extrapyramidal symptom-related treatment-emergent adverse events was low. Iloperidone is effective in treating patients with bipolar mania. The tolerability and safety profile of iloperidone in bipolar mania is consistent with previous clinical studies of patients with schizophrenia, and no new safety concerns were identified. ClinicalTrials.gov identifier: NCT04819776; EudraCT: 2020-000405-83.
Topics: Adult; Humans; Bipolar Disorder; Mania; Treatment Outcome; Antipsychotic Agents; Double-Blind Method; Psychiatric Status Rating Scales; Isoxazoles; Piperidines
PubMed: 38236020
DOI: 10.4088/JCP.23m14966 -
Cureus Jan 2024Introduction Schizophrenia symptom severity is linked to neuroinflammation. Certain blood cell indexes such as neutrophil-lymphocyte ratio (NLR) and neutrophil-albumin...
Introduction Schizophrenia symptom severity is linked to neuroinflammation. Certain blood cell indexes such as neutrophil-lymphocyte ratio (NLR) and neutrophil-albumin ratio (NAR) have been used as biomarkers in various diseases, including schizophrenia. In acute clinical practice, it is challenging to decide whether to provide intravenous antipsychotic treatment in some cases due to the lack of objective biomarkers of psychiatric symptoms. The NLR of individuals with schizophrenia is thought to be associated with disease severity, and changes in NLR may reflect a patient's response to antipsychotic treatment. We investigated the application of NLR as a biomarker for identifying acute severity and determining acute treatment response in patients with schizophrenia. Methods We retrospectively examined 251 inpatients diagnosed with schizophrenia and classified them according to treatment (intravenous haloperidol vs. oral antipsychotic medication during the acute phase) and investigated their NLR and NAR while receiving inpatient care. Results A total of 48 inpatients were given intravenous haloperidol to manage their acute symptoms; 208 were given oral antipsychotics. The intravenous haloperidol group experienced more severe symptoms, such as agitation and disorganized thinking, during the acute phase. Further, those who received intravenous haloperidol had significantly higher Clinical Global Impression-Severity (CGI-S) scores than the oral antipsychotic group. NLR and NAR were also significantly higher in the haloperidol intravenous group. Conclusion Elevated NLR and NAR could be easily measured in patients with psychomotor agitation who should be treated at any facility. Further, they are useful biomarkers for determining disease severity and the effects of treatment on psychomotor excitement in patients who require intravenous haloperidol.
PubMed: 38222994
DOI: 10.7759/cureus.52181 -
Neuropsychopharmacology Reports Mar 2024This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy,... (Meta-Analysis)
Meta-Analysis
AIM
This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants.
METHODS
Outcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non-response rate; the non-remission rate; all-cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain.
RESULTS
A literature search identified three double-blind, randomized, placebo-controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible-dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day.
CONCLUSIONS
Overall BRE showed similar utility to ARI and a good risk-benefit balance.
Topics: Humans; Aripiprazole; Depressive Disorder, Major; Japan; Psychomotor Agitation; Network Meta-Analysis; Weight Gain; Randomized Controlled Trials as Topic; Thiophenes; Quinolones
PubMed: 38219278
DOI: 10.1002/npr2.12414