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1.
Nat Commun ; 12(1): 781, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536416

RESUMO

After complete spinal cord injuries (SCI), spinal segments below the lesion maintain inter-segmental communication via the intraspinal propriospinal network. However, it is unknown whether selective manipulation of these circuits can restore locomotor function in the absence of brain-derived inputs. By taking advantage of the compromised blood-spinal cord barrier following SCI, we optimized a set of procedures in which AAV9 vectors administered via the tail vein efficiently transduce neurons in lesion-adjacent spinal segments after a thoracic crush injury in adult mice. With this method, we used chemogenetic actuators to alter the excitability of propriospinal neurons in the thoracic cord of the adult mice with a complete thoracic crush injury. We showed that activating these thoracic neurons enables consistent and significant hindlimb stepping improvement, whereas direct manipulations of the neurons in the lumbar spinal cord led to muscle spasms without meaningful locomotion. Strikingly, manipulating either excitatory or inhibitory propriospinal neurons in the thoracic levels leads to distinct behavioural outcomes, with preferential effects on standing or stepping, two key elements of the locomotor function. These results demonstrate a strategy of engaging thoracic propriospinal neurons to improve hindlimb function and provide insights into optimizing neuromodulation-based strategies for treating SCI.


Assuntos
Dependovirus/genética , Membro Posterior/fisiopatologia , Locomoção/fisiologia , Neurônios/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Animais , Antipsicóticos/administração & dosagem , Clozapina/administração & dosagem , Clozapina/análogos & derivados , Vetores Genéticos/genética , Membro Posterior/inervação , Locomoção/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/terapia
2.
BMJ Case Rep ; 14(2)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568409

RESUMO

A 75-year-old woman presents to the acute medical take with confusion and headache following a road traffic accident. She had previously been fit and well, living alone with no assistance. Following multiple investigations, she was diagnosed with Sturge-Weber Syndrome, a rare neurocutaneous disorder that usually presents with seizures in childhood. This case highlights an unusual example of this syndrome, presenting for the first time later in life.


Assuntos
Lamotrigina/uso terapêutico , Transtornos de Início Tardio/diagnóstico , Transtornos de Início Tardio/tratamento farmacológico , Transtornos de Início Tardio/fisiopatologia , Síndrome de Sturge-Weber/diagnóstico , Síndrome de Sturge-Weber/tratamento farmacológico , Síndrome de Sturge-Weber/fisiopatologia , Idoso , Antipsicóticos/uso terapêutico , Feminino , Humanos , Resultado do Tratamento
7.
Anticancer Res ; 41(2): 687-697, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517273

RESUMO

BACKGROUND/AIM: We investigated drugs that could sensitize P-glycoprotein (P-gp)-overexpressing drug-resistant cancer cells to vincristine (VIC) or eribulin treatment and assessed their associated mechanisms of action. MATERIALS AND METHODS: We investigated 15 bipolar drugs (quetiapine, risperidone, clozapine, asenapine, iloperidone, paliperidone, ziprasidone, trifluoperazine, loxapine succinate, pilocarpine, valproic acid, carbamazepine, levetiracetam, topiramate, and felbamate) to identify drugs with a sensitizing effect on VIC-resistant KBV20C cells at relatively low doses. Fluorescence-activated cell sorting (FACS), annexin V analyses, and rhodamine uptake tests were performed to further investigate the mechanism of action. RESULTS: We found that co-treatment with half the tested drugs (quetiapine, iloperidone, trifluoperazine, loxapine, risperidone, ziprasidone, or felbamate) at low doses could highly sensitize VIC-resistant KBV20C cells. With lower amounts of the bipolar drugs or VIC, we found that among the 15 bipolar drugs tested, 2 combinations (VIC-quetiapine and VIC-trifluoperazine) had much higher sensitization effects, suggesting that lower effective doses were sufficient for sensitizing P-gp-overexpressing resistant cells compared to those required with the other drugs. Furthermore, when we compared quetiapine and trifluoperazine to previously known bipolar drugs (fluphenazine, thioridazine, pimozide, or aripiprazole), we found that aripiprazole, administered at lower doses, had a much higher sensitization effect. We also demonstrated that co-treatment with another anti-mitotic drug (eribulin) increased the sensitization of KBV20C cells similar to VIC. We also found that aripiprazole had higher P-gp-inhibitory activity than the other bipolar drugs, indicating that this activity was involved in the higher level of VIC-aripiprazole sensitization. CONCLUSION: Co-treatment of anti-mitotic drug-resistant cancer cells with a low dose of aripiprazole had the strongest sensitization effect and is highly dependent on P-gp-inhibitory activity.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antipsicóticos/farmacologia , Aripiprazol/farmacologia , Reposicionamento de Medicamentos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Furanos/farmacologia , Cetonas/farmacologia , Neoplasias Bucais/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Vincristina/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
9.
Sr Care Pharm ; 36(2): 68-82, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33509330

RESUMO

When selecting and managing psychoactive medications in older people, it is equally important to focus on avoidance of toxicity as it is to focus on efficacy. Higher psychoactive medication load is associated with increased rate and risk of all cause hospitalization. The medication classes used to treat depression and related comorbidities include antidepressants, antipsychotics, stimulants, mood stabilizers, lithium, anxiolytics and sedative hypnotics. This discussion will examine considerations to help avoid medication related problems relevant to medications used to treat depression in the antidepressant pharmacological class.


Assuntos
Ansiolíticos/efeitos adversos , Antidepressivos/efeitos adversos , Antipsicóticos/efeitos adversos , Depressão/tratamento farmacológico , Psicotrópicos/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Humanos , Hipnóticos e Sedativos/efeitos adversos
10.
Br J Anaesth ; 126(2): 423-432, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33413977

RESUMO

Delirium and postoperative neurocognitive disorder are the commonest perioperative complications in patients more than 65 yr of age. However, data suggest that we often fail to screen patients for preoperative cognitive impairment, to warn patients and families of risk, and to take preventive measures to reduce the incidence of perioperative neurocognitive disorders. As part of the American Society of Anesthesiologists (ASA) Perioperative Brain Health Initiative, an international group of experts was invited to review published best practice statements and guidelines. The expert group aimed to achieve consensus on a small number of practical recommendations that could be implemented by anaesthetists and their partners to reduce the incidence of perioperative neurocognitive disorders. Six statements were selected based not only on the strength of the evidence, but also on the potential for impact and the feasibility of widespread implementation. The actions focus on education, cognitive and delirium screening, non-pharmacologic interventions, pain control, and avoidance of antipsychotics. Strategies for effective implementation are discussed. Anaesthetists should be key members of multidisciplinary perioperative care teams to implement these recommendations.


Assuntos
Anestesiologia/normas , Anestesistas/normas , Encéfalo/fisiopatologia , Cognição , Delírio/prevenção & controle , Equipe de Assistência ao Paciente/normas , Assistência Perioperatória/normas , Complicações Cognitivas Pós-Operatórias/prevenção & controle , Fatores Etários , Idoso , Antipsicóticos/efeitos adversos , Consenso , Delírio/fisiopatologia , Delírio/psicologia , Medicina Baseada em Evidências/normas , Humanos , Liderança , Pessoa de Meia-Idade , Complicações Cognitivas Pós-Operatórias/fisiopatologia , Complicações Cognitivas Pós-Operatórias/psicologia , Medição de Risco , Fatores de Risco
11.
Psychopharmacology (Berl) ; 238(2): 329-340, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33410987

RESUMO

RATIONALE: Management of anxiety, delirium, and agitation cannot be neglected in coronavirus disease (COVID-19). Antipsychotics are usually used for the pharmacological management of delirium, and confusion and behavioral disturbances. The concurrent use of treatments for COVID-19 and antipsychotics should consider eventual drug-drug interactions OBJECTIVE: To systematically review evidence-based available on drug-drug interactions between COVID-19 treatments and antipsychotics. EVIDENCE REVIEW: Three databases were consulted: Lexicomp® Drug Interactions, Micromedex® Solutions Drugs Interactions, and Liverpool© Drug Interaction Group for COVID-19 therapies. To acquire more information on QT prolongation and Torsade de Pointes (TdP), the CredibleMeds® QTDrugs List was searched. The authors made a recommendation agreed to by consensus. Additionally, a systematic review of drug-drug interactions between antipsychotics and COVID-19 treatment was conducted. RESULTS: The main interactions between COVID-19 drugs and antipsychotics are the risk of QT-prolongation and TdP, and cytochromes P450 interactions. Remdesivir, baricinitib, and anakinra can be used concomitantly with antipsychotics without risk of drug-drug interaction (except for hematological risk with clozapine and baricinitib). Favipiravir only needs caution with chlorpromazine and quetiapine. Tocilizumab is rather safe to use in combination with antipsychotics. The most demanding COVID-19 treatments for coadministration with antipsychotics are chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir because of the risk of QT prolongation and TdP and cytochromes interactions. The systematic review provides highly probable drug interaction between lopinavir/ritonavir plus quetiapine and ritonavir/indinavir plus risperidone. CONCLUSIONS: Clinicians prescribing antipsychotics should be aware of the likely risk of drug-drug interaction with COVID-19 medication and may benefit from taking into account present recommendations of use to preserve patient safety.


Assuntos
Antipsicóticos/efeitos adversos , Antivirais/efeitos adversos , /tratamento farmacológico , Antipsicóticos/uso terapêutico , Antivirais/uso terapêutico , Sistema Enzimático do Citocromo P-450 , Interações Medicamentosas , Humanos , Síndrome do QT Longo/induzido quimicamente , Torsades de Pointes/induzido quimicamente
12.
Mayo Clin Proc ; 96(1): 242-256, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33413822

RESUMO

Medications to treat disease and extend life in our patients often amass in quantities, resulting in what has been termed "polypharmacy." This imprecise label usually describes the accumulation of 5, and often more, medications. Polypharmacy in advancing age frequently results in drug therapy problems related to interactions, drug toxicity, falls with injury, delirium, and nonadherence. Polypharmacy is associated with resulting increased hospitalizations and higher costs of care for individuals and health care systems. To reduce polypharmacy, we delineate a systematic, consultative approach to identify highest-risk medications and drug-therapy problems. We address strategic reductions (deprescribing) of medications in palliative care, long-term care, and ambulatory older adults. Best practices for reducing opioids, benzodiazepines, and other high-risk medications include education about risk and agreement by patients and their families, advocates, and care teams. Addressing deprescribing should be within the framework of patients' health status as their care and goals transition from longevity to a plan of maintaining alertness, comfort, and satisfaction of quality of life. A team approach to address polypharmacy and avoidance of high-risk therapy is optimal within long-term care. Patients with terminal illnesses or those moving toward a comfort-care emphasis benefit from medication adjustments that are recognized beneficially within each patient's care goals. In caring for older adults, the acknowledgement that complicated regimens and high-risk medications requires a care plan to reduce or prevent medication-related problems and costs that are associated with polypharmacy.


Assuntos
Polimedicação , Idoso , Analgésicos Opioides/efeitos adversos , Antipsicóticos/efeitos adversos , Desprescrições , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Reconciliação de Medicamentos , Instituições de Cuidados Especializados de Enfermagem
14.
Biomed Pharmacother ; 133: 111087, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378980

RESUMO

Olanzapine is an atypical antipsychotic widely used for the treatment of schizophrenia, which often causes serious adverse drug reactions. Currently, there are no clinical guidelines implementing pharmacogenetic information on olanzapine. Moreover, the Dutch Pharmacogenomics Working Group (DPWG) states that CYP2D6 phenotype is not related to olanzapine response or side effects. Thus, the objective of this candidate-gene study was to investigate the effect of 72 polymorphisms in 21 genes on olanzapine pharmacokinetics and safety, including transporters (e.g. ABCB1, ABCC2, SLC22A1), receptors (e.g. DRD2, HTR2C), and enzymes (e.g. UGT, CYP and COMT), in a cohort of healthy volunteers. Polymorphisms in CYP2C9, SLC22A1, ABCB1, ABCC2, and APOC3 were related to olanzapine pharmacokinetic variability. The incidence of adverse reactions was related to several genes: palpitations to ABCB1 and SLC22A1, asthenia to ABCB1, somnolence to DRD2 and ABCB1, and dizziness to CYP2C9. However, further studies in patients are warranted to confirm the influence of these genetic polymorphisms on olanzapine pharmacokinetics and tolerability.


Assuntos
Antipsicóticos/farmacocinética , Enzimas/genética , Proteínas de Membrana Transportadoras/genética , Olanzapina/farmacocinética , Variantes Farmacogenômicos , Polimorfismo Genético , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Biotransformação , Ensaios Clínicos como Assunto , Feminino , Estudos de Associação Genética , Genótipo , Voluntários Saudáveis , Humanos , Masculino , Olanzapina/administração & dosagem , Olanzapina/efeitos adversos , Fenótipo , Fatores de Risco , Adulto Jovem
15.
Ann Pharmacother ; 55(1): 15-24, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32567359

RESUMO

BACKGROUND: Approximately 17% of intensive care unit (ICU) patients are prescribed at least 1 home neuropsychiatric medication (NPM). When abruptly discontinued, withdrawal symptoms may occur manifesting as agitation or delirium in the ICU setting. OBJECTIVE: To evaluate the impact of early reinitiation of NPMs. METHODS: This was a retrospective, observational cohort of adult ICU patients in a tertiary care hospital. Patients were included if admitted to the ICU and prescribed a NPM prior to arrival. Study groups were based on the timing of reinitiation of at least 50% of NPMs: ≤72 hours (early group) versus >72 hours (late group). RESULTS: The primary outcome was the proportion of patients with at least 1 agitation or delirium episode in the first 72 hours. Agitation and delirium were defined as at least 1 RASS assessment between +2 to +4 and a positive CAM-ICU assessment, respectively. A total of 300 patients were included, with 187 (62%) and 113 (38%) in the early and late groups, respectively. There was no difference in agitation or delirium (late 54 [48%] vs early 62 [33%]; adjusted odds ratio [aOR] = 1.5; 95% CI = 0.8-2.8; P = 0.193). Independent risk factors found to be associated with the primary outcome were restraints (aOR = 12.9; 95% CI = 6.9-24.0; P < 0.001) and benzodiazepines (BZDs; aOR = 2.0; 95% CI = 1.0-3.7; P = 0.038). CONCLUSIONS: After adjustment for baseline differences, there was no difference in agitation or delirium. Independent risk factors were restraint use and newly initiated BZDs.


Assuntos
Antipsicóticos/administração & dosagem , Delírio/prevenção & controle , Unidades de Terapia Intensiva , Agitação Psicomotora/prevenção & controle , Prevenção Secundária/métodos , Síndrome de Abstinência a Substâncias/prevenção & controle , Adulto , Idoso , Antipsicóticos/uso terapêutico , Benzodiazepinas/administração & dosagem , Benzodiazepinas/uso terapêutico , Estudos de Coortes , Cuidados Críticos , Delírio/diagnóstico , Substituição de Medicamentos , Feminino , Humanos , Masculino , Reconciliação de Medicamentos , Pessoa de Meia-Idade , Agitação Psicomotora/diagnóstico , Estudos Retrospectivos , Síndrome de Abstinência a Substâncias/diagnóstico
16.
Ann Pharmacother ; 55(1): 98-104, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32590907

RESUMO

OBJECTIVE: To provide a concise review of the new Food and Drug Administration (FDA)-approved antipsychotic, lumateperone, for use in schizophrenia. DATA SOURCES: A literature search of PubMed was performed (January 2000 to May 2020) using the following key terms: lumateperone, Caplyta, and ITI-007. Abstracts from conferences, review articles, clinical trials, and drug monographs were reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language monographs and studies conducted in humans were considered. DATA SYNTHESIS: Lumateperone was FDA approved for the treatment of schizophrenia in December 2019 based on 2 published randomized, double-blind, placebo-controlled trials. Lumateperone's pharmacology is consistent with that of other second-generation antipsychotics in that it has a higher affinity for the serotonin (5-HT2A) receptors compared with dopamine (D2) receptors but with lower affinities for α-1 and histaminergic receptors. In addition, it serves as a presynaptic dopamine partial agonist, serotonin reuptake inhibitor, and an indirect modulator of glutamatergic systems. Based on the 4-week clinical trials, lumateperone was well tolerated. Most common treatment-emergent adverse events were headache, somnolence, and dizziness. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: At this time, lumateperone had a statistically significant reduction in Positive and Negative Syndrome Scale when compared with placebo and was not significantly associated with the extrapyramidal symptoms (EPS) and metabolic adverse effects commonly seen with other antipsychotics. CONCLUSIONS: Lumateperone has the potential to benefit individuals with schizophrenia who are intolerant to the EPSs or metabolic adverse effects of other antipsychotics. However, further head-to-head trials with commercially available antipsychotics are still required to assist in establishing its role in treatment.


Assuntos
Antipsicóticos/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Esquizofrenia/tratamento farmacológico , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Antipsicóticos/farmacocinética , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration
17.
Clin Drug Investig ; 41(1): 99-113, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33331979

RESUMO

BACKGROUND AND OBJECTIVE: Long-acting injectable antipsychotics (LAIs) are associated with better treatment adherence and persistence than oral antipsychotics (OAPs) in patients with schizophrenia. However, real-world evidence assessing the impact of treatment with LAIs in Germany is limited. To fill this gap, we compared antipsychotic medication adherence and risk of treatment discontinuation (TD) among schizophrenia patients newly initiated on LAI or who switched their OAP regimen (overall cohort; OC). METHODS: Claims data of German schizophrenia patients who initiated LAIs or switched their OAP during 2012-2016 (index date) were retrospectively analyzed. Treatment switch was defined as add-on medication to existing prescription or terminating the existing prescription and initiating another OAP. Adherence and time to treatment discontinuation (TTD) were estimated. Determinants of treatment discontinuation were analyzed using two Cox regression models. Model 1 controlled for age, sex, and Charlson Comorbidity Index (CCI); model 2 also included insurance status, and medication, visit, and psychiatric inpatient stay costs. Sensitivity analysis on patients who terminated existing prescriptions and initiated new OAPs (complete switch cohort; CSC) was performed. RESULTS: In OC (n = 2650), LAI users had better adherence (35.4% vs. 11.6%), persistence (no 60-day gap; 40.7% vs. 19.8%), and longer TTD (median [95% confidence interval (CI)] 216 [193-249] vs. 50 [46-56] days) than OAP users. OAP usage (hazard ratio [HR] 1.89, 95% CI 1.73-2.06; p < 0.001) and greater CCI (HR 1.04, 95% CI 1.00-1.07; p = 0.023) were associated with greater risk of TD in model 1. Model 2 showed similar results. LAI users in CSC also had better adherence, persistence, and longer TTD. In CSC too, OAP usage and greater CCI were associated with greater risk of TD in model 1, but only CCI was significant in model 2. Higher pre-index psychiatric inpatient costs were associated with lower risk of TD (HR 0.99, 95% CI 0.98-1.00; p = 0.014). LIMITATIONS: Inherent limitations of claims data and lack of control on OAP administration may have influenced the results. CONCLUSION: This real-world study associates LAIs with better medication adherence and lower antipsychotic discontinuation risk than OAPs.


Assuntos
Antipsicóticos/administração & dosagem , Adesão à Medicação , Esquizofrenia/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Idoso , Estudos de Coortes , Preparações de Ação Retardada/administração & dosagem , Feminino , Alemanha , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
18.
Life Sci ; 266: 118889, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33310043

RESUMO

AIM: The coronavirus disease 2019 (COVID-19) pandemic has swept the globe and no specific effective drug has been identified. Drug repurposing is a well-known method to address the crisis in a time-critical fashion. Antipsychotic drugs (APDs) have been reported to inhibit DNA replication of hepatitis B virus, measles virus germination, and HIV infection, along with replication of SARS-CoV and MERS-CoV, both of which interact with host cells as SARS-CoV-2. METHODS: Nineteen APDs were screened using ACE2-HEK293T cell membrane chromatography (ACE2-HEK293T/CMC). Cytotoxicity assay, coronavirus spike pseudotype virus entry assay, surface plasmon resonance, and virtual molecular docking were applied to detect affinity between ACE2 protein and drugs and a potential antiviral property of the screened compounds. KEY FINDINGS: After the CMC screening, 8 of the 19 APDs were well-retained on ACE2-HEK293T/CMC column and showed significant antiviral activities in vitro. Three quarters of them belong to phenothiazine and could significantly inhibit the entrance of coronavirus into ACE2-HEK293T cells. Aother two drugs, aripiprazole and tiapride, exhibited weaker inhibition. We selected five of the drugs for subsequent evaluation. All five showed similar affinity to ACE2 and virtual molecular docking demonstrated they bound with different amino acids respectively on ACE2 which SARS-CoV-2 binds to. SIGNIFICANCE: Eight APDs were screened for binding with ACE2, five of which demonstrated potential protective effects against SARS-CoV-2 through acting on ACE2. Although the five drugs have a weak ability to block SARS-CoV-2 with a single binding site, they may provide a synergistic effect in adjuvant therapy of COVID-19 infection.


Assuntos
/metabolismo , Antipsicóticos/farmacologia , Antivirais/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , /efeitos dos fármacos , /antagonistas & inibidores , Antipsicóticos/química , Antipsicóticos/metabolismo , Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida/métodos , Reposicionamento de Medicamentos , Células HEK293 , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Glicoproteína da Espícula de Coronavírus/metabolismo , Ressonância de Plasmônio de Superfície , Internalização do Vírus/efeitos dos fármacos
20.
J Frailty Aging ; 10(1): 22-30, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33331618

RESUMO

The implementation of effective interventions for neuropsychiatric symptoms (NPS) is perceived as one of the most pressing research priorities in the field of dementia and one of the main unmet needs from the perspective of affected individuals and their caregivers and relatives. Nevertheless, to date, only a relatively marginal part of dementia research has focused on NPS. This study aimed to describe and discuss the state of the art concerning the identification and development of new pharmacological treatments for NPS in dementia. A review of 320 ongoing phase 1, 2, 3, and 4 protocols registered in the clinicaltrials.gov database was performed. All the trials enrolling patients with dementia were selected. Only studies adopting clinical measures of NPS frequency and/or severity as primary outcome were retained and analyzed. Overall, only a minority of ongoing phase 1, 2, 3 and 4 protocols on dementia (i.e., 9.0%) is primarily targeting NPS. Most of these studies are adopting a placebo-controlled parallel assignment design, testing oral compounds, and targeting specific NPS (mostly agitation and/or aggression). A total of 3,445 subjects with dementia will tentatively be recruited in these trials. The methodologies adopted in these studies, the characteristics of the tested interventions, the eligibility criteria, and the operational definitions of NPS are presented and discussed. The relevance of NPS is not yet matched by an adequate research effort. The current tendency at privileging disease-modifying approaches and other symptoms of dementia and the methodological complexity of studying NPS are still substantially contributing to the gap between research activities and clinical needs.


Assuntos
Demência/tratamento farmacológico , Atenção Primária à Saúde/métodos , Agitação Psicomotora/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Cuidadores/psicologia , Ensaios Clínicos como Assunto , Demência/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Testes Neuropsicológicos
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