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Brain & Spine 2024TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on... (Review)
Review
INTRODUCTION
TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on mortality is about 10% across all ages. Amantadine hydrochloride is one of the most commonly prescribed medications for patients undergoing inpatient neurorehabilitation who have disorders of consciousness. It is a dopamine (DA) receptor agonist and a N-Methyl-D-aspartate (NMDA) receptor antagonist via dopamine release and dopamine reuptake inhibition. The current study will synthesize the current available evidence and show the effect of Amantadine in functional improvement after TBI.
RESEARCH QUESTION
Does Amantadine have an effect on functional improvement of TBI patients?
MATERIAL AND METHODS
This systematic review included all randomized placebo-controlled trials that compare the use of Amantadine versus placebo for functional improvement of patients after TBI. Outcome measures included DRS, GCS and/or GOS scores.
RESULTS
Three studies with a total of 281 patients were included in the quantitative analyses. GRADE assessments show that there was a high certainty of evidence for functional improvement in terms of DRS scores.
DISCUSSION AND CONCLUSION
Evidence of this review show that the use of Amantadine may have a beneficial effect on functional outcome in moderate to severe traumatic brain injuries among adult patients. Given the still-limited body of knowledge, more relevant studies must be made exploring the impact of Amantadine therapies on promoting functional recovery within the brain injury rehabilitation care continuum, with the goals of achieving larger sample sizes and establishing the early- or later-treatment beneficial effects.
PubMed: 38465280
DOI: 10.1016/j.bas.2024.102773 -
Frontiers in Neurology 2024Tardive dyskinesia (TD) is a movement disorder that can arise as a side effect of treatment with dopamine receptor-blocking agents (DRBAs), including antipsychotic drugs...
Tardive dyskinesia (TD) is a movement disorder that can arise as a side effect of treatment with dopamine receptor-blocking agents (DRBAs), including antipsychotic drugs (APDs) used to manage psychotic illnesses. Second-generation APDs (SGAs) are often preferred to first-generation drugs due to their lower propensity to cause TD, however many SGAs-treated patients still develop the condition. Although TD is a global health concern, evidence regarding the occurrence of TD and how it is managed in Asian countries is currently limited. This article reports the results of a systematic review of the published literature on TD focusing on its prevalence, types of patients, knowledge of the condition, causative factors, and usual treatment pathways in clinical practice in Asian countries. Epidemiological data suggest that the prevalence of TD is increasing globally due to an overall rise in APD use, contributing factors being polypharmacy with multiple APDs, the use of higher than necessary doses, and off-label use for non-psychotic indications. Although exact prevalence figures for TD in Asian countries are difficult to define, there is a similar pattern of rising APD use which will result in increasing numbers of TD patients in this region. These issues need to be addressed and strategies developed to minimize TD risk and manage this disabling condition which impacts patients' quality of life and daily functioning. To date, both research into TD has been predominantly psychiatry focused and the perspectives from neurologists regarding the clinical management of this challenging condition are scarce. However, neurologists have an essential role in managing the movement disorders manifestations that characterize TD. Optimum management of TD, therefore, should ideally involve collaboration between psychiatrists and neurologists in joint care pathways, wherever practical. Collaborative pathways are proposed in this article, and the challenges that will need to be addressed in Asian countries to improve the care of people with TD are highlighted, with a focus on the neurologist's viewpoint and the implications for the management of TD globally.
PubMed: 38419696
DOI: 10.3389/fneur.2024.1356761 -
Journal of Psychiatry & Neuroscience :... 2024Transcranial magnetic stimulation (TMS) is a noninvasive neurostimulation modality that has been used to study human synaptic plasticity. Leveraging work in ex vivo...
BACKGROUND
Transcranial magnetic stimulation (TMS) is a noninvasive neurostimulation modality that has been used to study human synaptic plasticity. Leveraging work in ex vivo preparations, mechanistically informed pharmacological adjuncts to TMS have been used to improve our fundamental understanding of TMS-induced synaptic plasticity.
METHODS
We systematically reviewed the literature pairing pharmacological adjuncts with TMS plasticity-induction protocols in humans. We searched MEDLINE, PsycINFO, and Embase from 2013 to Mar. 10, 2023. Studies published before 2013 were extracted from a previous systematic review. We included studies using repetitive TMS, theta-burst stimulation, paired associative stimulation, and quadripulse stimulation paradigms in healthy and clinical populations.
RESULTS
Thirty-six studies met our inclusion criteria (28 in healthy and 8 in clinical populations). Most pharmacological agents have targeted the glutamatergic -methyl-d-aspartate (NMDA; 15 studies) or dopamine receptors (13 studies). The NMDA receptor is necessary for TMS-induced plasticity; however, sufficiency has not been shown across protocols. Dopaminergic modulation of TMS-induced plasticity appears to be dose-dependent. The GABAergic, cholinergic, noradrenergic, and serotonergic neurotransmitter systems have small evidence bases supporting modulation of TMS-induced plasticity, as do voltage-gated calcium and sodium channels. Studies in clinical populations suggest that pharmacological adjuncts to TMS may rescue motor cortex plasticity, with implications for therapeutic applications of TMS and a promising clinical trial in depression.
LIMITATIONS
This review is limited by the predominance in the literature of studies with small sample sizes and crossover designs.
CONCLUSION
Pharmacologically enhanced TMS largely parallels findings from ex vivo preparations. As this area expands and novel targets are tested, adequately powered samples in healthy and clinical populations will inform the mechanisms of TMS-induced plasticity in health and disease.
Topics: Humans; Transcranial Magnetic Stimulation; Neuronal Plasticity; Motor Cortex; Dopamine; Calcium; Evoked Potentials, Motor
PubMed: 38359933
DOI: 10.1503/jpn.230090 -
BMJ Neurology Open 2024The aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists...
BACKGROUND
The aim of this manuscript is to review the evidence and compare the efficacy and safety of catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists (DRAs) and monoamine-oxidase B inhibitors (MAOB-Is) as adjunctive treatment to levodopa in patients with Parkinson's disease (PD) experiencing motor complications.
METHODS
In this systematic review and network meta-analysis, literature searches were performed in MEDLINE and Embase to identify eligible randomised controlled trials (RCTs) with a minimal follow-up of at least 4 weeks published in English between 1980 and 2021. RCTs were included if either a COMT-I, DRA or MAOB-I was evaluated as an adjunctive therapy to levodopa in patients with PD experiencing motor complications and dyskinesia. The main outcomes included daily off-medication time, motor and non-motor examination scales, and adverse events including dyskinesia.
RESULTS
74 RCTs reporting on 18 693 patients were included. All three studied drug classes decreased daily off-medication time compared with placebo (COMT-Is mean -0.8 hours (95% CI -1.0 to -0.6), DRAs -1.1 hours (95% CI -1.4 to -0.8), MAOB-Is -0.9 hours (95% CI -1.2 to -0.6)). Safety analysis showed an increased risk of dyskinesia for all three drug classes (COMT-Is OR 3.3 (95% CI 2.7 to 4.0), DRAs 3.0 (95% CI 2.5 to 3.5), MAOB-Is 1.6 (95% CI 1.2 to 2.2)). According to surface under the cumulative ranking curve scores, pramipexole IR was associated with the most favourable benefit-risk profile.
CONCLUSIONS
COMT-Is, DRAs and MAOB-Is effectively reduce motor complications and increase incidence of dyskinesia. In the network meta-analysis, adjunctive use of DRAs appeared most effective.
PubMed: 38352047
DOI: 10.1136/bmjno-2023-000573 -
Psychopharmacology Feb 2024Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Dopamine antagonists induce dopamine receptor supersensitivity. This may manifest in late-appearing movement disorders (tardive dyskinesia (TD). VMAT-2 inhibitors reduce dopaminergic transmission but have limited activity at postsynaptic receptors and so may have antipsychotic activity with lower risk of tardive dyskinesia.
METHODS
We conducted a systematic database search from inception to September 2022 for articles describing the use of VMAT-2 inhibitors in psychosis. Inclusion criteria were as follows: Population: adults diagnosed with psychosis or schizophrenia; Intervention: treatment with tetrabenazine, deutetrabenazine or valbenazine; Comparison: comparison with placebo or/and antipsychotic drug; Outcomes: with efficacy outcomes (e.g. Brief Psychiatric Rating Scale (BPRS) change or clinician assessment) and adverse effects ratings (e.g. rating scale or clinician assessment or dropouts); and Studies: in randomised controlled trials and non-randomised studies.
RESULTS
We identified 4892 records relating to VMAT-2 inhibitor use of which 5 (173 participants) met our a priori meta-analysis inclusion criteria. VMAT-2 inhibitors were more effective than placebo for the outcome 'slight improvement' (risk ratio (RR) = 1.77 (95% CI 1.03, 3.04)) but not for 'moderate improvement' (RR 2.81 (95% CI 0.27, 29.17). VMAT-2 inhibitors were as effective as active comparators on both measures for-'slight improvement' (RR 1.05 (95% CI 0.6, 1.81)) and 'moderate improvement' (RR 1.11 (95% CI 0.51, 2.42). Antipsychotic efficacy was also suggested by a narrative review of 37 studies excluded from the meta-analysis.
CONCLUSIONS
VMAT-2 inhibitors may have antipsychotic activity and may offer promise for treatment of psychosis with the potential for a reduced risk of TD.
Topics: Adult; Humans; Antipsychotic Agents; Psychotic Disorders; Schizophrenia; Tardive Dyskinesia; Tetrabenazine; Vesicular Monoamine Transport Proteins
PubMed: 38238580
DOI: 10.1007/s00213-023-06488-3 -
Expert Review of Clinical Pharmacology Jan 2024Quetiapine exhibits notable pharmacokinetic and pharmacodynamic (PK/PD) variability, the origins of which are poorly understood. This systematic review summarizes... (Review)
Review
INTRODUCTION
Quetiapine exhibits notable pharmacokinetic and pharmacodynamic (PK/PD) variability, the origins of which are poorly understood. This systematic review summarizes published population PK/PD studies and identifies significant covariates accounting for this variability to inform precision dosing.
METHODS
We systematically searched the PubMed, Web of Science, and Embase databases and compared study characteristics, model parameters, and covariate effects. Visual predictive distributions were used to compare different models. Forest plots and Monte Carlo simulations were used to assess the influence of covariates.
RESULTS
Six population PK and three population PK/PD studies were included. The median apparent clearance in adults was 87.7 L/h. Strong and moderate cytochrome P450 3A4 inducers increased the apparent clearance approximately fourfold, while strong cytochrome P450 3A4 inhibitors reduced it by 93%. The half-maximum effect concentrations were 82.8 ng/mL for the Brief Psychiatric Rating Scale and 583 ng/mL for dopamine D receptor occupancy. Both treatment duration and quetiapine exposure were associated with weight gain.
CONCLUSIONS
Concurrent administration of potent or moderate CYP3A4 inducers and inhibitors need to be avoided in quetiapine-treated patients. When co-medication is required, it is recommended to adjust the dosage based on therapeutic drug monitoring. Additional research is warranted to delineate the dose-exposure-response relationships of quetiapine and active metabolite norquetiapine in pediatrics, geriatrics, hepatically-impaired patients, and women using contraceptives or are pregnant or menopausal.
PROSPERO REGISTRATION
CRD42023446654.
Topics: Adult; Humans; Female; Child; Quetiapine Fumarate; Cytochrome P-450 Enzyme System; Models, Biological
PubMed: 38108086
DOI: 10.1080/17512433.2023.2295428 -
Therapeutic Drug Monitoring Feb 2024Positron emission tomography (PET) and single photon emission tomography (SPECT) of molecular drug targets (neuroreceptors and transporters) provide essential...
BACKGROUND
Positron emission tomography (PET) and single photon emission tomography (SPECT) of molecular drug targets (neuroreceptors and transporters) provide essential information for therapeutic drug monitoring-guided antipsychotic drug therapy. The optimal therapeutic windows for D 2 antagonists and partial agonists, as well as their proposed target ranges, are discussed based on an up-to-date literature search.
METHODS
This part I of II presents an overview of molecular neuroimaging studies in humans and primates involving the target engagement of amisulpride, haloperidol, clozapine, aripiprazole, olanzapine, quetiapine, risperidone, cariprazine, and ziprasidone. The systemic review particularly focused on dopamine D 2 -like and 5-HT 2A receptors. Target concentration ranges were estimated based on receptor occupancy ranges that relate to clinical effects or side effects (ie, extrapyramidal side effects). In addition, findings for other relevant receptor systems were included to further enrich the discussion.
RESULTS
The reported reference ranges for aripiprazole and clozapine align closely with findings from PET studies. Conversely, for haloperidol, risperidone, and olanzapine, the PET studies indicate that a lowering of the previously published upper limits would be necessary to decrease the risk of extrapyramidal side effect.
CONCLUSIONS
Molecular neuroimaging studies serve as a strong tool for defining target ranges for antipsychotic drug treatment and directing therapeutic drug monitoring.
Topics: Humans; Antipsychotic Agents; Olanzapine; Risperidone; Clozapine; Aripiprazole; Haloperidol; Schizophrenia; Positron-Emission Tomography; Benzodiazepines
PubMed: 38018857
DOI: 10.1097/FTD.0000000000001131 -
Journal of Clinical PsychopharmacologyIncreasing evidence suggests an association between third-generation antipsychotics (TGAs) and impulse control disorders (ICDs). This is thought to be due to their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increasing evidence suggests an association between third-generation antipsychotics (TGAs) and impulse control disorders (ICDs). This is thought to be due to their partial agonism of dopamine receptors. However, neither the relative nor absolute risks of ICDs in those prescribed TGAs are well established. To inform clinical practice, this systematic review and meta-analysis summarizes and quantifies the current evidence for an association.
METHODS
An electronic search of Medline, PsychINFO, EMBASE, and the Cochrane Clinical Trials Database was undertaken from database inception to November 2022. Three reviewers screened abstracts and reviewed full texts for inclusion. A random-effects meta-analysis was conducted with eligible studies.
RESULTS
A total of 392 abstracts were retrieved, 214 remained after duplicates were removed. Fifteen full texts were reviewed, of which 8 were included. All 8 studies found that TGAs were associated with increased probability of ICDs. Risk of bias was high or critical in 7 of 8 studies. Three studies were included in the pooled analysis for the primary outcome, 2 with data on each of aripiprazole, cariprazine, and brexpiprazole. Exposure to TGAs versus other antipsychotics was associated with an increase in ICDs (pooled odds ratio, 5.54; 2.24-13.68). Cariprazine and brexpiprazole were significantly associated with ICDs when analyzed individually. Aripiprazole trended toward increased risk, but very wide confidence intervals included no effect.
CONCLUSIONS
Third-generation antipsychotics were associated with increased risk of ICDs in all studies included and pooled analysis. However, the risk of bias is high, confidence intervals are wide, and the quality of evidence is very low for all TGAs examined.
Topics: Humans; Antipsychotic Agents; Aripiprazole; Disruptive, Impulse Control, and Conduct Disorders; Risk Factors
PubMed: 38011021
DOI: 10.1097/JCP.0000000000001773 -
Journal of Diabetes and Metabolic... Dec 2023The Dopamine-2 receptor agonists, Bromocriptine and Cabergoline, were originally introduced for prolactinomas, pituitary tumors, and parkinson's disease but have... (Review)
Review
BACKGROUND
The Dopamine-2 receptor agonists, Bromocriptine and Cabergoline, were originally introduced for prolactinomas, pituitary tumors, and parkinson's disease but have glucose-lowering effects. This paper systematically reviewed the significance of their effects on lowering blood glucose level and conducted a comprehensive systematic search to identify relevant clinical trials of dopamine 2 agonists on glycated hemoglobin (HbA1c) and fasting blood sugar (FBS).
METHOD
We conducted a systematic review search in the databases (PubMed, Google Scholar, Cochrane Library, Registers, and Citations) until November 30, 2022, using the PRISMA 2020 statement. The Oxford quality score (Jadad score) was used to assess the study's quality. The present study protocol was registered on the PROSPERO database with ID: CRD42023389582. The study included studies with full abstracts, predefined doses, clear interventions, and blood glucose measurements.
RESULT
Data were synthesized from 23 clinical studies that recruited 6125 study subjects. The pooled effect analysis of the clinical trials revealed that dopamine 2 agonists improved HbA1c [SMD = -1.26; 95% CI (-1.60, -0.93), < .00001], and FBS [SMD = -1.84; 95% CI (-2.61, -1.07), < .00001]. Each drug's pooled effect analysis indicates bromocriptine significantly improved HbA1c [SMD = -1.25; 95% CI (-1.64, -0.87), < .00001] and FBS [SMD = -1.90; 95% CI (-2.79, -1.01), < .00001] and similarly, cabergoline significantly improved HbA1c [SMD = -1.29; 95% CI (-1.96, -0.62), < .00001] and FBS [SMD = -1.62; 95% CI (-2.82, -0.41), < .00001]. The pooled and individual analyses demonstrated that dopamine 2 agonists have a significant ability to lower blood glucose levels in clinical studies.
CONCLUSION
This study shows that dopamine 2 agonists significantly lowered FBS and HbA1c levels without causing severe negative effects. Even though the results are promising, additional research is necessary to establish the appropriate antihyperglycemic dosage, frequency of daily use, side effects, and potential product interactions when employing dopamine 2 receptor agonists for their antihyperglycemic effect.
PubMed: 37975084
DOI: 10.1007/s40200-023-01230-4 -
The European Journal of Neuroscience Mar 2024Dopamine, a catecholamine neurotransmitter, has historically been associated with the encoding of reward, whereas its role in aversion has received less attention. Here,...
Dopamine, a catecholamine neurotransmitter, has historically been associated with the encoding of reward, whereas its role in aversion has received less attention. Here, we systematically gathered the vast evidence of the role of dopamine in the simplest forms of aversive learning: classical fear conditioning and extinction. In the past, crude methods were used to augment or inhibit dopamine to study its relationship with fear conditioning and extinction. More advanced techniques such as conditional genetic, chemogenic and optogenetic approaches now provide causal evidence for dopamine's role in these learning processes. Dopamine neurons encode conditioned stimuli during fear conditioning and extinction and convey the signal via activation of D receptor sites particularly in the amygdala, prefrontal cortex and striatum. The coordinated activation of dopamine receptors allows for the continuous formation, consolidation, retrieval and updating of fear and extinction memory in a dynamic and reciprocal manner. Based on the reviewed literature, we conclude that dopamine is crucial for the encoding of classical fear conditioning and extinction and contributes in a way that is comparable to its role in encoding reward.
Topics: Dopamine; Extinction, Psychological; Conditioning, Classical; Fear; Prefrontal Cortex; Avoidance Learning
PubMed: 37848184
DOI: 10.1111/ejn.16157