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Psychiatry Research Dec 2021The purpose of this systematic review and meta-analysis was to assess adherence and persistence to long-acting injectable dopamine receptor blocking agents (LAI DRBAs)... (Meta-Analysis)
Meta-Analysis Review
Adherence and persistence to long-acting injectable dopamine receptor blocking agent therapy in the United States: A systematic review and meta-analysis of cohort studies.
The purpose of this systematic review and meta-analysis was to assess adherence and persistence to long-acting injectable dopamine receptor blocking agents (LAI DRBAs) in published observational cohort studies conducted in the United States. Adherence rate (proportion of days covered ≥80%) and persistence rate (no gap in therapy ≥60 days) to LAI DRBAs were examined in 26 articles for qualitative review and 8 articles for quantitative review. There was significant variability in adherence and persistence rates to LAI DRBAs in the reported observational cohort studies. The mean adherence and persistence rates to LAI DRBAs in the included studies were 36% (8-66%) and 56% (32-80%), respectively. The use of LAI DRBAs showed cumulative benefit of achieving adherence 1.40 times higher compared to oral agents. The persistence rate was measured by number of patients having no more than 60 days gap in therapy at follow-up, and the cumulative benefit of being persistently on the therapy was 1.65 times higher among the LAI agents-exposed group compared to the oral agents-exposed group. The use of LAI DRBAs confers benefit in adherence and persistence compared to oral DRBA formulations.
Topics: Antipsychotic Agents; Delayed-Action Preparations; Dopamine Antagonists; Humans; Medication Adherence; Observational Studies as Topic; Receptors, Dopamine; Schizophrenia; United States
PubMed: 34808495
DOI: 10.1016/j.psychres.2021.114277 -
JAMA Dermatology Aug 2020The association between the use of medications and the development of bullous pemphigoid (BP) is unclear. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The association between the use of medications and the development of bullous pemphigoid (BP) is unclear.
OBJECTIVE
To assess the associations between previous exposure to certain medications and BP.
DATA SOURCES
For this systematic review and meta-analysis, PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched for relevant studies from inception to February 20, 2020.
STUDY SELECTION
Case-control or cohort studies and randomized clinical trials that examined the odds or risk of BP in patients with previous medication use were included. No geographic or language limitations were imposed.
DATA EXTRACTION AND SYNTHESIS
The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline was followed. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of included observational studies; Cochrane Collaboration's tool was used for randomized clinical trials. Aggregate data were used to conduct a random-effects model meta-analysis if the included studies were sufficiently homogenous. Subgroup analyses were performed for use of various medications of the same category.
MAIN OUTCOMES AND MEASURES
Odds ratio (OR), hazard ratio, and risk ratio of bullous pemphigoid in association with medication use.
RESULTS
This meta-analysis included 13 case-control studies, 1 cohort study, and 1 randomized clinical trial with a total of 285 884 participants. The meta-analysis of case-control studies showed a significant association of BP with previous use of aldosterone antagonists (pooled OR, 1.75; 95% CI, 1.28-2.40), dipeptidyl peptidase 4 inhibitors (pooled OR, 1.92; 95% CI, 1.55-2.38), anticholinergics (pooled OR, 3.12; 95% CI, 1.54-6.33), and dopaminergic medications (pooled OR, 2.03; 95% CI, 1.34-3.05). One cohort study found an increased risk of BP among patients receiving dipeptidyl peptidase 4 inhibitors (hazard ratio, 2.38; 95% CI, 1.16-4.88; P = .02). One trial found a higher occurrence of BP in patients with diabetes receiving linagliptin (0.2% in diabetes group vs 0% in the placebo group).
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis suggest that aldosterone antagonists, dipeptidyl peptidase 4 inhibitors, anticholinergics, and dopaminergic medications are associated with BP. These medications should be judiciously prescribed, particularly in high-risk patients who are elderly and have disabling neurologic disorders.
Topics: Antihypertensive Agents; Cholinergic Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Diuretics; Dopamine Agents; Humans; Hypoglycemic Agents; Mineralocorticoid Receptor Antagonists; Odds Ratio; Pemphigoid, Bullous; Psychotropic Drugs; Risk Factors
PubMed: 32584924
DOI: 10.1001/jamadermatol.2020.1587 -
Brain and Behavior Jun 2023Primary generalized dystonia due to the DYT1 gene is an autosomal dominant disorder caused by a GAG deletion on chromosome 9q34. It is a well-defined, genetically... (Review)
Review
BACKGROUND
Primary generalized dystonia due to the DYT1 gene is an autosomal dominant disorder caused by a GAG deletion on chromosome 9q34. It is a well-defined, genetically proven, isolated dystonia syndrome. However, its pathophysiology remains unclear.
OBJECTIVES
This study was aimed at profiling the functional neuroimaging findings in DYT1 dystonia and harmonizing the pathophysiological implications for DYT1 dystonia from the standpoint of different neuroimaging techniques.
METHODS
A systematic review was conducted using identified studies published in English from Medline, PsycINFO, Embase, CINAHL, and the Cochrane Database of Systematic Reviews (CDSR), between 1985 and December 2019 (PROSPERO protocol CRD42018111211).
RESULTS
All DYT1 gene carriers irrespective of clinical penetrance have reduced striatal GABA, dopamine receptors and increased metabolic activity in the lentiform nucleus, supplementary motor area, and cerebellum in addition to an abnormal cerebellothalamocortical pathway. Nonmanifesting carriers on the other hand have a disruption of the distal (thalamocortical) segment and have larger putaminal volumes than manifesting carriers and healthy controls. Activation of the midbrain, thalamus, and sensorimotor cortex was only found in the manifesting carriers.
CONCLUSIONS
Therefore, we propose that DYT1 dystonia is a cerebellostriatothalamocortical network disorder affecting either the structure or function of the different structures or nodes in the network.
Topics: Humans; Dystonia; Dystonic Disorders; Molecular Chaperones; Neuroimaging
PubMed: 37165749
DOI: 10.1002/brb3.3023 -
Frontiers in Immunology 2023Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even... (Review)
Review
Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even endanger life. Acupuncture is widely accepted and applied in the treatment of sepsis, and breakthroughs have been made regarding its mechanism of action in recent years. In this review, we systematically discuss the current clinical applications of acupuncture in the treatment of sepsis and focus on the mechanisms of acupuncture in animal models of systemic inflammation. In clinical research, acupuncture can not only effectively inhibit excessive inflammatory reactions but also improve the immunosuppressive state of patients with sepsis, thus maintaining immune homeostasis. Mechanistically, a change in the acupoint microenvironment is the initial response link for acupuncture to take effect, whereas PROKR2 neurons, high-threshold thin nerve fibres, cannabinoid CB2 receptor (CB2R) activation, and Ca influx are the key material bases. The cholinergic anti-inflammatory pathway of the vagus nervous system, the adrenal dopamine anti-inflammatory pathway, and the sympathetic nervous system are key to the transmission of acupuncture information and the inhibition of systemic inflammation. In MODS, acupuncture protects against septic organ damage by inhibiting excessive inflammatory reactions, resisting oxidative stress, protecting mitochondrial function, and reducing apoptosis and tissue or organ damage.
Topics: Animals; Humans; Sepsis; Acupuncture Therapy; Inflammation; Vagus Nerve
PubMed: 37753078
DOI: 10.3389/fimmu.2023.1242640 -
International Journal of Molecular... Mar 2023Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain... (Review)
Review
Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.
Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain connectivity. Antipsychotics are the primary pharmacological treatment after more than sixty years after their introduction in therapy. Two findings hold true for all presently available antipsychotics. First, all antipsychotics occupy the dopamine D2 receptor (D2R) as an antagonist or partial agonist, even if with different affinity; second, D2R occupancy is the necessary and probably the sufficient mechanism for antipsychotic effect despite the complexity of antipsychotics' receptor profile. D2R occupancy is followed by coincident or divergent intracellular mechanisms, implying the contribution of cAMP regulation, β-arrestin recruitment, and phospholipase A activation, to quote some of the mechanisms considered canonical. However, in recent years, novel mechanisms related to dopamine function beyond or together with D2R occupancy have emerged. Among these potentially non-canonical mechanisms, the role of Na channels at the dopamine at the presynaptic site, dopamine transporter (DAT) involvement as the main regulator of dopamine concentration at synaptic clefts, and the putative role of antipsychotics as chaperones for intracellular D2R sequestration, should be included. These mechanisms expand the fundamental role of dopamine in schizophrenia therapy and may have relevance to considering putatively new strategies for treatment-resistant schizophrenia (TRS), an extremely severe condition epidemiologically relevant and affecting almost 30% of schizophrenia patients. Here, we performed a critical evaluation of the role of antipsychotics in synaptic plasticity, focusing on their canonical and non-canonical mechanisms of action relevant to the treatment of schizophrenia and their subsequent implication for the pathophysiology and potential therapy of TRS.
Topics: Humans; Antipsychotic Agents; Dopamine; Schizophrenia; Schizophrenia, Treatment-Resistant; beta-Arrestins
PubMed: 36983018
DOI: 10.3390/ijms24065945 -
European Journal of Neurology Aug 2023Tremor is often perceived as severely disabling by patients with idiopathic Parkinson's disease (iPD) and yet ranges among the most difficult symptoms to treat. To date,... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Tremor is often perceived as severely disabling by patients with idiopathic Parkinson's disease (iPD) and yet ranges among the most difficult symptoms to treat. To date, no comprehensive analysis of non-lesional therapies to manage tremor in iPD exists to base recommendations upon. We therefore present a systematic literature review and meta-analysis assessing the efficacy/effectiveness and safety of non-lesional treatments for tremor in iPD.
METHODS
Three electronic databases were searched using a combination of title/abstract keywords complemented by hand-searching of reference lists. A random-effects meta-analysis of standardized mean change scores was conducted where appropriate.
RESULTS
Some 114 studies met inclusion criteria involving 8045 patients. The meta-analysis revealed an overall reduction of standardized mean change scores by (-0.93 [CI: -1.42; -0.43], p < 0.001) by 14 different dopaminergic and non-dopaminergic classes of agents. No significant differences were identified between direct comparisons. Subgroup analysis comparing dopamine receptor agonists resulted in superior effects of pramipexole and rotigotine compared with ropinirole. There was little cumulative evidence to support the use of individual non-pharmacological interventions for tremor, except for electrical stimulation.
CONCLUSIONS
The results of this meta-analysis suggest a large but nonspecific effect of established pharmacological therapies on tremor in iPD. Based on high-quality studies, there is sufficient evidence to support that levodopa, dopamine receptor agonists, and monoamine oxidase inhibitors provide tremor relief in most patients, while evidence supporting other treatments is less well established. Sufficient evidence to draw conclusions on effects of non-lesional treatments in cases with refractory tremor is lacking.
Topics: Humans; Parkinson Disease; Dopamine Agonists; Antiparkinson Agents; Tremor; Levodopa
PubMed: 37154268
DOI: 10.1111/ene.15823 -
Pharmacological Reviews Oct 2022Transcranial magnetic stimulation (TMS) is a noninvasive neuromodulation tool currently used as a treatment in multiple psychiatric and neurologic disorders. Despite its... (Review)
Review
Changing Cerebral Blood Flow, Glucose Metabolism, and Dopamine Binding Through Transcranial Magnetic Stimulation: A Systematic Review of Transcranial Magnetic Stimulation-Positron Emission Tomography Literature.
Transcranial magnetic stimulation (TMS) is a noninvasive neuromodulation tool currently used as a treatment in multiple psychiatric and neurologic disorders. Despite its widespread use, we have an incomplete understanding of the way in which acute and chronic sessions of TMS affect various neural and vascular systems. This systematic review summarizes the state of our knowledge regarding the effects TMS may be having on cerebral blood flow, glucose metabolism, and neurotransmitter release. Forty-five studies were identified. Several key themes emerged: 1) TMS transiently increases cerebral blood flow in the area under the coil; 2) TMS to the prefrontal cortex increases glucose metabolism in the anterior cingulate cortex of patients with depression; and 3) TMS to the motor cortex and prefrontal cortex decreases dopamine receptor availability in the ipsilateral putamen and caudate respectively. There is, however, a paucity of literature regarding the effects TMS may have on other neurotransmitter and neuropeptide systems of interest, all of which may shed vital light on existing biologic mechanisms and future therapeutic development. SIGNIFICANCE STATEMENT: Transcranial magnetic stimulation (TMS) is a noninvasive neuromodulation tool currently used as a treatment in multiple psychiatric and neurologic disorders. This systematic review summarizes the state of our knowledge regarding the effects TMS on cerebral blood flow, glucose metabolism, and neurotransmitter release.
Topics: Humans; Transcranial Magnetic Stimulation; Dopamine; Tomography, X-Ray Computed; Positron-Emission Tomography; Cerebrovascular Circulation; Glucose
PubMed: 36779330
DOI: 10.1124/pharmrev.122.000579 -
Journal of Affective Disorders May 2023Many studies have performed assessments of genetic variants in the D2 dopamine receptor (DRD2) gene as risk factors for post-traumatic stress disorder (PTSD) and major... (Meta-Analysis)
Meta-Analysis
Assessment of genetic variants in D2 dopamine receptor (DRD2) gene as risk factors for post-traumatic stress disorder (PTSD) and major depressive disorder (MDD): A systematic review and meta-analysis.
BACKGROUND
Many studies have performed assessments of genetic variants in the D2 dopamine receptor (DRD2) gene as risk factors for post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). However, the results are inconsistent. This meta-analysis aimed to systematically summarize published data to evaluate the reliable association between the DRD2 genetic variants and the risk of PTSD and MDD.
METHODS
A systematic literature search was conducted using the Web of Science, PubMed, Google Scholar, Excerpta Medica Database (EMBASE), Springer, ScienceDirect, Wiley Online Library, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database (CBM), WANFANG Data, CQVIP, and Chinese National Knowledge Infrastructure (CNKI) databases before January 1st, 2022.
RESULTS
A total of 27 genetic variants in the DRD2 gene were retrieved, and 7 of them met the inclusion criteria for meta-analysis. Our meta-analysis results indicated that the rs1800497 (TaqIA) polymorphism was significantly associated with the increased risk of PTSD (Dominant model (A1A1 + A1A2 vs. A2A2): OR = 1.49, 95 % CI, 1.08-2.04 Z = 2.46, P = 0.014). Subgroup analysis for ethnicity suggested that a significantly increased risk of PTSD was observed in Asians (Dominant model (A1A1 + A1A2 vs. A2A2): OR = 1.39, 95 % CI, 1.08-1.79, Z = 2.60, P = 0.009) and Caucasians (Dominant model (A1A1 + A1A2 vs. A2A2): OR = 1.87, 95 % CI 1.02-3.41, Z = 2.04, P = 0.042). Meanwhile, we detected significant association strengths between the rs1799978 and rs2075652 polymorphisms in the DRD2 gene and MDD (for rs1799978, Homozygote comparison (GG vs. AA): OR = 0.60, 95 % CI = 0.37-0.97, Z = 2.08, P = 0.038; for rs2075652, Homozygote comparison (AA vs. GG): OR = 1.82, 95 % CI = 1.32-2.50, Z = 3.67, P < 0.001). Our cumulative meta-analyses indicated a continuous trend toward association strength with PTSD and MDD.
CONCLUSIONS
This meta-analysis indicated that genetic variants in the DRD2 gene might potentially contribute to genetic susceptibility for PTSD and MDD. The utilization of DRD2 genetic variants as risk factors for PTSD and MDD requires further validation by large well-designed case-control studies.
Topics: Humans; Depressive Disorder, Major; Stress Disorders, Post-Traumatic; Polymorphism, Genetic; Risk Factors; Genetic Predisposition to Disease; Receptors, Dopamine D2
PubMed: 36740143
DOI: 10.1016/j.jad.2023.02.001 -
Biomolecules Jun 2022Schizophrenia has been conceptualized as a neurodevelopmental disorder with synaptic alterations and aberrant cortical-subcortical connections. Antipsychotics are the... (Review)
Review
Schizophrenia has been conceptualized as a neurodevelopmental disorder with synaptic alterations and aberrant cortical-subcortical connections. Antipsychotics are the mainstay of schizophrenia treatment and nearly all share the common feature of dopamine D2 receptor occupancy, whereas glutamatergic abnormalities are not targeted by the presently available therapies. D-amino acids, acting as N-methyl-D-aspartate receptor (NMDAR) modulators, have emerged in the last few years as a potential augmentation strategy in those cases of schizophrenia that do not respond well to antipsychotics, a condition defined as treatment-resistant schizophrenia (TRS), affecting almost 30-40% of patients, and characterized by serious cognitive deficits and functional impairment. In the present systematic review, we address with a direct and reverse translational perspective the efficacy of D-amino acids, including D-serine, D-aspartate, and D-alanine, in poor responders. The impact of these molecules on the synaptic architecture is also considered in the light of dendritic spine changes reported in schizophrenia and antipsychotics' effect on postsynaptic density proteins. Moreover, we describe compounds targeting D-amino acid oxidase and D-aspartate oxidase enzymes. Finally, other drugs acting at NMDAR and proxy of D-amino acids function, such as D-cycloserine, sarcosine, and glycine, are considered in the light of the clinical burden of TRS, together with other emerging molecules.
Topics: Amino Acids; Antipsychotic Agents; Humans; Neurobiology; Receptors, N-Methyl-D-Aspartate; Schizophrenia; Schizophrenia, Treatment-Resistant
PubMed: 35883465
DOI: 10.3390/biom12070909 -
Neuroscience and Biobehavioral Reviews Nov 2019A major hypothesis in the addiction field suggests deficits in dopamine signaling during abstinence as a driving mechanism for the relapsing course of the disorder....
A major hypothesis in the addiction field suggests deficits in dopamine signaling during abstinence as a driving mechanism for the relapsing course of the disorder. Paradoxically, blockade of mu-opioid receptors (MORs) intended to suppress dopamine release and alcohol reward is a widely used treatment for preventing relapse in alcohol use disorder (AUD). To elucidate this apparent discrepancy, we systematically survey the literature on experimental studies in AUD subjects and animal models, which assessed striatal dopamine levels and D1, D2-like receptor, dopamine transporter and MOR via positron emission tomography (PET) and ex vivo receptor binding assays. The reported evidence indicates a changing dopaminergic signaling over time, which is associated with concomitant alterations in MOR, thus suggesting a highly dynamic regulation of the reward system during abstinence. Such a view can reconcile the various evidences from in vivo and postmortem studies, but makes developing an effective pharmacological intervention that specifically targets either dopamine receptors or the transporter system a daunting task.
Topics: Alcoholism; Animals; Autopsy; Craving; Humans; Positron-Emission Tomography; Receptors, Dopamine; Receptors, Opioid, mu; Reward
PubMed: 30243576
DOI: 10.1016/j.neubiorev.2018.09.010