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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 -
Headache Jan 2016We sought to conduct a qualitative systematic review to evaluate the safety and efficacy of available treatments for pediatric patients with migraine or benign primary... (Review)
Review
OBJECTIVE
We sought to conduct a qualitative systematic review to evaluate the safety and efficacy of available treatments for pediatric patients with migraine or benign primary headache in the emergency department, in an effort to inform future practice.
METHODS
Scopus, Medline, and PubMed databases were searched for randomized controlled trials retrospective reviews, review articles, and case studies discussing migraine or benign primary headache management that were conducted in the emergency room or outpatient acute care setting in pediatric patients (less than 18-years old). Meeting abstracts and cited references within articles were also evaluated. Multiple variables were recorded, including type of treatment, study design, dosing, primary outcome, and side effects. Therapeutic gain was calculated in studies with a placebo arm. Treatments were subjectively assessed based on methodology and number of trials for a particular therapy.
RESULTS
Thirty-one studies were included in the final analysis. Of these, 17 were randomized controlled trials, 9 were retrospective reviews, and 5 were prospective chart review studies. One pertained to IV fluids, 2 to nonspecific analgesic use, 5 to dopamine receptor antagonists, 2 to valproic acid, 1 to propofol, 1 to magnesium, 1 to bupivicaine, 13 to triptan medications, and 3 to dihydroergotamine (DHE). Treatments considered effective for acute migraine or benign primary headache in the analgesic category include ibuprofen, and to a lesser degree acetaminophen. Ketorolac was not compared to other NSAIDs, but was found to be less effective than prochlorperazine. Of the phenothiazines, prochlorperazine was considered most effective. Of the triptan medications, almotriptan, rizatriptan, zolmitriptan nasal spray, sumatriptan nasal spray, and combination sumatriptan/naproxen are effective agents for acute treatment. Treatments considered probably effective included IV fluids, chlorpromazine, valproate sodium, injectable sumatriptan, and IV DHE. Treatments with oral zolmitriptan showed inconsistent results, while treatments considered ineffective included isolated oral sumatriptan and oral DHE. There is insufficient evidence to comment on propofol, magnesium, and bupivicaine efficacy.
CONCLUSIONS
Of the available evidence, ibuprofen, prochlorperazine, and certain triptan medications are the most effective and safe agents for acute management of migraine and other benign headache disorders in the pediatric population. Additional studies in this population are needed, and should take into consideration variables such as dosing, co-administered medications, treatment duration, and length of treatment effect.
Topics: Child; Child, Preschool; Emergency Service, Hospital; Humans; Migraine Disorders; Pediatrics; Treatment Outcome
PubMed: 26790849
DOI: 10.1111/head.12746 -
Sleep Attacks in Patients With Parkinson's Disease on Dopaminergic Medications: A Systematic Review.Movement Disorders Clinical Practice Dec 2014Dopaminergic medications are used as first-line treatment for Parkinson's disease (PD). In 1999, a case series was published describing 9 patients who took dopamine... (Review)
Review
Dopaminergic medications are used as first-line treatment for Parkinson's disease (PD). In 1999, a case series was published describing 9 patients who took dopamine agonists (pramipexole or ropinirole) and experienced sudden irresistible sleep attacks. Sleep attacks have subsequently been reported with other dopaminergic medications, including levodopa. Because these symptoms might not be rare and can affect health-related quality of life, we set out to review the prevalence and clinical characteristics of sleep attacks in patients with PD on dopaminergic medications. We conducted a systematic literature review using the terms parkinson* AND dopamine* AND narcolep* OR sleep attack in multiple databases (PubMed, Embase, and PsycINFO). The systematic literature review yielded 23 relevant articles, including nine case reports or case series and 14 original studies. According to the pooled data from the five studies reporting prevalence figures (n = 10,084), sleep attacks occur in 13.0% of patients with PD on dopaminergic medications. Our analysis failed to show significant differences in the Epworth Sleepiness scores between patients with and without sleep attacks (mean difference: 2.92; 95% confidence interval: -0.47-6.31). The I value of 76% indicated high heterogeneity among the studies. Sleep attacks are not a rare occurrence in patients with PD on dopamine agonist treatment. We found conflicting results on whether sleep attacks in PD resemble narcolepsy. The pathophysiology of these symptoms might be related to dopamine D2 and D4 receptor gene polymorphisms. The most effective management strategies were dose reduction and discontinuation of the offending drugs.
PubMed: 30363881
DOI: 10.1002/mdc3.12063 -
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 -
Journal of Neurotrauma Jul 2017This systematic review examined the association between genetics and risk for sustaining a traumatic brain injury. We retrieved articles published in English from 1980... (Review)
Review
This systematic review examined the association between genetics and risk for sustaining a traumatic brain injury. We retrieved articles published in English from 1980 to July 2016 obtained from the online databases PubMed, PsycINFO, MEDLINE, Embase, and Web of Science. In total 5903 articles were identified, 77 underwent full-text screening, and 6 were included in this review. Five studies examined the risk of concussion associated with apolipoprotein E alleles (APOE-ɛ2, ɛ3,ɛ4), and polymorphisms of the APOE promoter (rs405509), brain derived neurotrophic factor (BDNF, rs6265), and dopamine receptor D2 (DRD2, rs1800497) were each considered in two studies. Microtubule associated protein tau (TAU exon 6 polymorphisms His47Tyr [rs2258689] and Ser53Pro [rs10445337]), and neurofilament heavy (NEHF, rs165602) genotypic variants, were the focus of single studies. No study showed an increased risk associated solely with the presence of the APOE-ɛ4 allele, nor were there any significant findings for the NEFH, TAU, or DRD2 genotypic variants. Two studies examined the APOE promoter -219G/T polymorphism in athletes, and both found an association with concussion. Both BDNF studies also found a significant association with concussion incidence; United States soldiers with the Met/Met genotype were more likely to report a history of concussion prior to deployment and to sustain a concussion during deployment. We conclude that the APOE promoter -219G/T polymorphism and the BDNF Met/Met genotype might confer risk for sustaining a TBI. Based on research to date, the APOE-ɛ4 allele does not appear to influence risk. More research is needed to determine if these findings replicate.
Topics: Alleles; Apolipoproteins E; Brain Concussion; Brain-Derived Neurotrophic Factor; Genetic Predisposition to Disease; Genotype; Humans; Polymorphism, Genetic; Receptors, Dopamine D2; Risk Factors
PubMed: 28100103
DOI: 10.1089/neu.2016.4833 -
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 -
Schizophrenia Bulletin Nov 2016Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of... (Meta-Analysis)
Meta-Analysis Review
Although weight gain is a serious but variable adverse effect of antipsychotics that has genetic underpinnings, a comprehensive meta-analysis of pharmacogenetics of antipsychotic-related weight gain is missing. In this review, random effects meta-analyses were conducted for dominant and recessive models on associations of specific single nucleotide polymorphisms (SNP) with prospectively assessed antipsychotic-related weight or body mass index (BMI) changes (primary outcome), or categorical increases in weight or BMI (≥7%; secondary outcome). Published studies, identified via systematic database search (last search: December 31, 2014), plus 3 additional cohorts, including 222 antipsychotic-naïve youth, and 81 and 141 first-episode schizophrenia adults, each with patient-level data at 3 or 4 months treatment, were meta-analyzed. Altogether, 72 articles reporting on 46 non-duplicated samples (n = 6700, mean follow-up = 25.1wk) with 38 SNPs from 20 genes/genomic regions were meta-analyzed (for each meta-analysis, studies = 2-20, n = 81-2082). Eleven SNPs from 8 genes were significantly associated with weight or BMI change, and 4 SNPs from 2 genes were significantly associated with categorical weight or BMI increase. Combined, 13 SNPs from 9 genes (Adrenoceptor Alpha-2A [ADRA2A], Adrenoceptor Beta 3 [ADRB3], Brain-Derived Neurotrophic Factor [BDNF], Dopamine Receptor D2 [DRD2], Guanine Nucleotide Binding Protein [GNB3], 5-Hydroxytryptamine (Serotonin) Receptor 2C [HTR2C], Insulin-induced gene 2 [INSIG2], Melanocortin-4 Receptor [MC4R], and Synaptosomal-associated protein, 25kDa [SNAP25]) were significantly associated with antipsychotic-related weight gain (P-values < .05-.001). SNPs in ADRA2A, DRD2, HTR2C, and MC4R had the largest effect sizes (Hedges' g's = 0.30-0.80, ORs = 1.47-1.96). Less prior antipsychotic exposure (pediatric or first episode patients) and short follow-up (1-2 mo) were associated with larger effect sizes. Individual antipsychotics did not significantly moderate effect sizes. In conclusion, antipsychotic-related weight gain is polygenic and associated with specific genetic variants, especially in genes coding for antipsychotic pharmacodynamic targets.
Topics: Antipsychotic Agents; Humans; Pharmacogenetics; Psychotic Disorders; Weight Gain
PubMed: 27217270
DOI: 10.1093/schbul/sbw058 -
Progress in Neuro-psychopharmacology &... Dec 2020Global reports estimate the number of betel quid (BQ) chewers up to 600 million. The proportion of betel quid dependence (BQD) is 20%-90% among current users. BQD...
BACKGROUND
Global reports estimate the number of betel quid (BQ) chewers up to 600 million. The proportion of betel quid dependence (BQD) is 20%-90% among current users. BQD mechanisms are not fully understood, and no pharmacological solution exists for its cessation therapy.
METHODS
We present a systematic review on BQD mechanisms and examine potential cessation therapeutic drugs. We conducted a systematic literature search in PubMed and Web of Science databases and identified the latest 10 years' relevant articles for reviews.
RESULTS
Functional magnetic resonance imaging results demonstrate that neurological mechanisms link the brain reward, cognitive, and impulsive systems in BQ or BQD users. The use of the areca nut increases both brain serotonin and noradrenaline levels, whereas arecoline, a potentially addictive areca nut component, has monoamine oxidase-A (MAO-A) inhibitor-like properties. MAO-A inhibitors prevent neurotransmitter breakdown and increase dopamine and serotonin concentrations in the brain. A reduction of daily BQ use was observed among patients with depression after antidepressant therapy, including MAO-A inhibitor and selective serotonin reuptake inhibitor (SSRI). Arecoline is a nicotinic acetylcholine receptor agonist expressed in Xenopus oocytes. However, relatively negligible amounts of nicotine are detected in the areca nut.
CONCLUSION
In conclusion, the current evidence provides a better understanding of the neurological and pharmacological mechanisms behind BQD. Arecoline, an MAO-A inhibitor, may account for BQD. Future translational studies are needed to verify the efficacy of potential BQD cessation drugs. MAO-A inhibitor and SSRI would thus be potentially promising targets for clinical trials.
Topics: Animals; Areca; Arecoline; Behavior, Addictive; Brain Chemistry; Humans; Magnetic Resonance Imaging; Monoamine Oxidase Inhibitors; Substance-Related Disorders
PubMed: 32454163
DOI: 10.1016/j.pnpbp.2020.109982