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Molecular Psychiatry Aug 2023Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic... (Meta-Analysis)
Meta-Analysis
Antipsychotic drugs differ in their propensity to cause extrapyramidal side-effects (EPS), but their dose-effects are unclear. Therefore, we conducted a systematic review and dose-response meta-analysis. We searched multiple electronic databases up to 20.02.2023 for fixed-dose studies investigating 16 second-generation antipsychotics and haloperidol (all formulations and administration routes) in adults with acute exacerbations of schizophrenia. The primary outcome was the number of participants receiving antiparkinsonian medication, and if not available, the number of participants with extrapyramidal side-effects (EPS) and the mean scores of EPS rating scales were used as proxies. The effect-size was odds ratio (ORs) compared with placebo. One-stage random-effects dose-response meta-analyses with restricted cubic splines were conducted to estimate the dose-response curves. We also examined the relationship between dopamine D receptor (DR) occupancy and ORs by estimating occupancies from administrated doses. We included data from 110 studies with 382 dose arms (37193 participants). Most studies were short-term with median duration of 6 weeks (range 3-26 weeks). Almost all antipsychotics were associated with dose-dependent EPS with varied degrees and the maximum ORs ranged from OR = 1.57 95%CI [0.97, 2.56] for aripiprazole to OR = 7.56 95%CI [3.16, 18.08] for haloperidol at 30 mg/d. Exceptions were quetiapine and sertindole with negligible risks across all doses. There was very low quality of findings for cariprazine, iloperidone, and zotepine, and no data for clozapine. The DR occupancy curves showed that the risk increased substantially when DR occupancy exceeded 75-85%, except for DR partial agonists that had smaller ORs albeit high DR occupancies. In conclusion, we found that the risk of EPS increases with rising doses and differs substantially in magnitude among antipsychotics, yet exceptions were quetiapine and sertindole with negligible risks. Our data provided additional insights into the current DR therapeutic window for EPS.
Topics: Adult; Humans; Antipsychotic Agents; Quetiapine Fumarate; Haloperidol; Clozapine; Receptors, Dopamine D2; Drug-Related Side Effects and Adverse Reactions
PubMed: 37537284
DOI: 10.1038/s41380-023-02203-y -
PloS One 2015International guidelines recommend dopamine or norepinephrine as first-line vasopressor agents in septic shock. Phenylephrine, epinephrine, vasopressin and terlipressin... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
International guidelines recommend dopamine or norepinephrine as first-line vasopressor agents in septic shock. Phenylephrine, epinephrine, vasopressin and terlipressin are considered second-line agents. Our objective was to assess the evidence for the efficiency and safety of all vasopressors in septic shock.
METHODS
Systematic review and meta-analysis. We searched electronic database of MEDLINE, CENTRAL, LILACS and conference proceedings up to June 2014. We included randomized controlled trials comparing different vasopressors for the treatment of adult patients with septic shock. Primary outcome was all-cause mortality. Other clinical and hemodynamic measurements were extracted as secondary outcomes. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) were pooled.
RESULTS
Thirty-two trials (3,544 patients) were included. Compared to dopamine (866 patients, 450 events), norepinephrine (832 patients, 376 events) was associated with decreased all-cause mortality, RR 0.89 (95% CI 0.81-0.98), corresponding to an absolute risk reduction of 11% and number needed to treat of 9. Norepinephrine was associated with lower risk for major adverse events and cardiac arrhythmias compared to dopamine. No other mortality benefit was demonstrated for the comparisons of norepinephrine to epinephrine, phenylephrine and vasopressin / terlipressin. Hemodynamic data were similar between the different vasopressors, with some advantage for norepinephrine in central venous pressure, urinary output and blood lactate levels.
CONCLUSIONS
Evidence suggests a survival benefit, better hemodynamic profile and reduced adverse events rate for norepinephrine over dopamine. Norepinephrine should be regarded as the first line vasopressor in the treatment of septic shock.
Topics: Epinephrine; Hemodynamics; Humans; Lypressin; Norepinephrine; Phenylephrine; Shock, Septic; Terlipressin; Treatment Outcome; Vasoconstrictor Agents; Vasopressins
PubMed: 26237037
DOI: 10.1371/journal.pone.0129305 -
Psychiatria Polska 2016BPSD (Behavioral and Psychological Symptoms in Dementia) affects virtually all patients with dementia. The aim of this review is to present information on epidemiology,... (Review)
Review
BPSD (Behavioral and Psychological Symptoms in Dementia) affects virtually all patients with dementia. The aim of this review is to present information on epidemiology, consequences and evidence-based non-pharmacological and pharmacological treatment approaches. The review also covers recent literature derived from a systematic literature Medline search on BPSD. Results indicate that BPSD are major risk factors for an earlier placement of affected individuals in nursing homes and a potentially more severe course of dementia over time. Treatment of BPSD is complex and includes both strategies.
Topics: Aggression; Anticonvulsants; Antipsychotic Agents; Behavioral Symptoms; Clinical Protocols; Conduct Disorder; Dementia; Dopamine Antagonists; Female; Geriatric Psychiatry; Humans; Male; Neurocognitive Disorders; Severity of Illness Index
PubMed: 27847922
DOI: 10.12740/PP/64477 -
Gastroenterology Apr 2023Although there have been multiple drugs tested in gastroparesis, their relative efficacy and safety are unknown. We evaluated this in a network meta-analysis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Although there have been multiple drugs tested in gastroparesis, their relative efficacy and safety are unknown. We evaluated this in a network meta-analysis of randomized controlled trials (RCTs).
METHODS
We searched the literature to September 7, 2022. We judged the efficacy of drugs based on global symptoms of gastroparesis; individual symptoms, including nausea, vomiting, abdominal pain, bloating, or fullness; and safety according to total adverse events and adverse events leading to withdrawal. We extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures and reporting pooled relative risks (RRs) of not improving with 95% confidence intervals (CIs), ranking drugs according to P-score.
RESULTS
We identified 29 RCTs (3772 patients). Based on global symptoms, clebopride ranked first for efficacy (RR, 0.30; 95% CI, 0.16-0.57; P-score = .99) followed by domperidone (RR, 0.68; 95% CI, 0.48-0.98; P-score = .76). No other drug was superior to placebo. Only 2 drug classes were efficacious: in rank order, oral dopamine antagonists (RR, 0.58; 95% CI, 0.44-0.77; P-score = .96) and tachykinin-1 antagonists (RR, 0.69; 95% CI, 0.52-0.93; P-score = .83). For individual symptoms, oral metoclopramide ranked first for nausea (RR 0.46; 95% CI, 0.21-1.00; P-score = .95), fullness (RR 0.67; 95% CI, 0.35-1.28; P-score = .86), and bloating (RR 0.53; 95% CI, 0.30-0.93; P-score = .97), based on only 1 small trial. Only prucalopride was more likely to be associated with adverse events than placebo.
CONCLUSIONS
In a network meta-analysis, oral dopamine antagonists and tachykinin-1 antagonists were more efficacious than placebo for gastroparesis, but confidence in the evidence was low to moderate for most comparisons. There is an unmet need for efficacious therapies for gastroparesis.
Topics: Humans; Gastroparesis; Network Meta-Analysis; Nausea; Dopamine Antagonists; Tachykinins
PubMed: 36581089
DOI: 10.1053/j.gastro.2022.12.014 -
International Journal of Molecular... Jan 2022This review investigates the association between vitamin D and sleep disorders. Vitamin D is an essential nutrient known to play an important role in the growth and bone... (Review)
Review
This review investigates the association between vitamin D and sleep disorders. Vitamin D is an essential nutrient known to play an important role in the growth and bone health of the human body, but it also appears to play a role in sleep. The goal of our review is to examine the association between vitamin D and sleep disorders in children and adolescents. We summarize the evidence about the role and the mechanism of action of vitamin D in children and adolescents with sleep disorders such as insomnia, obstructive sleep apnea (OSA), restless legs syndrome (RLS), and other sleep disorders. Systematic electronic database searches were conducted using Pubmed and Cochrane Library. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The studies that met the established inclusion criteria were analyzed and compared. Results suggest a strict relationship between vitamin D deficiency in children and sleep disorders. There is evidence that vitamin D is implicated in the different neurochemical mechanisms involved in sleep regulation and mainly in the serotonergic and dopaminergic pathways. This might be responsible for the association of vitamin D deficiency and restless sleep, sleep hyperhidrosis, OSA, and RLS.
Topics: Adolescent; Child; Dopamine; Female; Humans; Male; Serotonin; Sleep Wake Disorders; Vitamin D Deficiency
PubMed: 35163353
DOI: 10.3390/ijms23031430 -
Molecular Psychiatry Jul 2016The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies... (Meta-Analysis)
Meta-Analysis Review
The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies in clinical samples as well as twin studies suggest a familial liability and consequently different genes were investigated in association studies. Pharmacotherapy with methylphenidate (MPH) seems to be the first-line treatment of choice in adults with attention-deficit hyperactive disorder (ADHD) and some studies were conducted on the genes influencing the response to this drug. Finally some peripheral biomarkers were identified in ADHD adult patients. We believe this work is the first systematic review and meta-analysis of candidate gene association studies, pharmacogenetic and biochemical (metabolomics) studies performed in adults with ADHD to identify potential genetic, predictive and peripheral markers linked specifically to ADHD in adults. After screening 5129 records, we selected 87 studies of which 61 were available for candidate gene association studies, 5 for pharmacogenetics and 21 for biochemical studies. Of these, 15 genetic, 2 pharmacogenetic and 6 biochemical studies were included in the meta-analyses. We obtained an association between adult ADHD and the gene BAIAP2 (brain-specific angiogenesis inhibitor 1-associated protein 2), even after Bonferroni correction, with any heterogeneity in effect size and no publication bias. If we did not apply the Bonferroni correction, a trend was found for the carriers allele 9R of dopamine transporter SLC6A3 40 bp variable tandem repeat polymorphism (VNTR) and for 6/6 homozygotes of SLC6A3 30 bp VNTR. Negative results were obtained for the 9-6 haplotype, the dopamine receptor DRD4 48 bp VNTR, and the enzyme COMT SNP rs4680. Concerning pharmacogenetic studies, no association was found for the SLC6A3 40 bp and response to MPH with only two studies selected. For the metabolomics studies, no differences between ADHD adults and controls were found for salivary cortisol, whereas lower serum docosahexaenoic acid (DHA) levels were found in ADHD adults. This last association was significant even after Bonferroni correction and in absence of heterogeneity. Other polyunsaturated fatty acids (PUFAs) such as AA (arachidonic acid), EPA (eicosapentaenoic acid) and DyLA (dihomogammalinolenic acid) levels were not different between patients and controls. No publication biases were observed for these markers. Genes linked to dopaminergic, serotoninergic and noradrenergic signaling, metabolism (DBH, TPH1, TPH2, DDC, MAOA, MAOB, BCHE and TH), neurodevelopment (BDNF and others), the SNARE system and other forty genes/proteins related to different pathways were not meta-analyzed due to insufficient data. In conclusion, we found that there were not enough genetic, pharmacogenetic and biochemical studies of ADHD in adults and that more investigations are needed. Moreover we confirmed a significant role of BAIAP2 and DHA in the etiology of ADHD exclusively in adults. Future research should be focused on the replication of these findings and to assess their specificity for ADHD.
Topics: Adult; Alleles; Attention Deficit Disorder with Hyperactivity; Biomarkers; Docosahexaenoic Acids; Dopamine Plasma Membrane Transport Proteins; Female; Gene Frequency; Genetic Association Studies; Genotype; Humans; Male; Methylphenidate; Minisatellite Repeats; Nerve Tissue Proteins; Pharmacogenetics; Polymorphism, Genetic; Receptors, Dopamine D4
PubMed: 27217152
DOI: 10.1038/mp.2016.74 -
The Journal of Emergency Medicine Oct 2017Chlorpromazine is the only drug approved by the US Food and Drug Administration for the treatment of hiccups; however, many other pharmacologic treatments have been... (Review)
Review
BACKGROUND
Chlorpromazine is the only drug approved by the US Food and Drug Administration for the treatment of hiccups; however, many other pharmacologic treatments have been proposed for intractable and persistent hiccups. Currently, there is little evidence to support the use of one agent over another.
OBJECTIVE
This review aims to identify literature concerning the use of pharmacologic treatments for intractable and persistent hiccups with the goal of evaluating therapies in terms of their level of evidence, mechanism of action, efficacy, dosing, onset of action, and adverse effects.
METHODS
A systematic literature search of PubMed, Embase, the Cochrane Library, and the New York Academy of Medicine was performed to find articles where a pharmacologic agent was used to treat intractable or persistent hiccups between the years 1966 and 2016. The GRADE method was used to assess the level of evidence for the studies included in this review.
RESULTS
This review identified 26 articles involving 10 pharmacologic treatment options that met our inclusion criteria. Amitriptyline, baclofen, gabapentin, haloperidol, metoclopramide, midazolam, nifedipine, nimodipine, orphenadrine, and valproic acid were found in the literature to be successful in treating hiccups.
CONCLUSION
Baclofen, gabapentin, and metoclopramide were the only agents that were studied in a prospective manner, while only baclofen and metoclopramide were studied in randomized controlled trials. No specific recommendations can be made for treating intractable and persistent hiccups with the evidence currently available in the literature. Therapy selection should be specific to individual patients, their underlying comorbidities, etiology of hiccups, and take into account the individual properties of the drugs.
Topics: Adrenergic Uptake Inhibitors; Chlorpromazine; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Emergency Service, Hospital; GABA-B Receptor Agonists; Hiccup; Humans
PubMed: 29079070
DOI: 10.1016/j.jemermed.2017.05.033 -
Genetics of borderline personality disorder: systematic review and proposal of an integrative model.Neuroscience and Biobehavioral Reviews Mar 2014Borderline personality disorder (BPD) is one of the most common mental disorders and is characterized by a pervasive pattern of emotional lability, impulsivity,... (Review)
Review
Borderline personality disorder (BPD) is one of the most common mental disorders and is characterized by a pervasive pattern of emotional lability, impulsivity, interpersonal difficulties, identity disturbances, and disturbed cognition. Here, we performed a systematic review of the literature concerning the genetics of BPD, including familial and twin studies, association studies, and gene-environment interaction studies. Moreover, meta-analyses were performed when at least two case-control studies testing the same polymorphism were available. For each gene variant, a pooled odds ratio (OR) was calculated using fixed or random effects models. Familial and twin studies largely support the potential role of a genetic vulnerability at the root of BPD, with an estimated heritability of approximately 40%. Moreover, there is evidence for both gene-environment interactions and correlations. However, association studies for BPD are sparse, making it difficult to draw clear conclusions. According to our meta-analysis, no significant associations were found for the serotonin transporter gene, the tryptophan hydroxylase 1 gene, or the serotonin 1B receptor gene. We hypothesize that such a discrepancy (negative association studies but high heritability of the disorder) could be understandable through a paradigm shift, in which "plasticity" genes (rather than "vulnerability" genes) would be involved. Such a framework postulates a balance between positive and negative events, which interact with plasticity genes in the genesis of BPD.
Topics: Animals; Borderline Personality Disorder; Catechol O-Methyltransferase; Databases, Factual; Dopamine; Gene-Environment Interaction; Genetic Association Studies; Genetic Predisposition to Disease; Genetics; Humans; Serotonin
PubMed: 24456942
DOI: 10.1016/j.neubiorev.2014.01.003 -
BMJ Clinical Evidence Oct 2011Depression may affect 2% to 8% of children and adolescents, with a peak incidence around puberty. It may be self-limiting, but about 40% of affected children experience... (Review)
Review
INTRODUCTION
Depression may affect 2% to 8% of children and adolescents, with a peak incidence around puberty. It may be self-limiting, but about 40% of affected children experience a recurrent attack, one third of affected children will make a suicide attempt, and 3% to 4% will die from suicide.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmacological, psychological, combination, and complementary treatments for depression in children and adolescents? What are the effects of treatments for refractory depression in children and adolescents? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: citalopram, cognitive behavioural therapy (CBT) (individual or group, to prevent relapse), electroconvulsive therapy, escitalopram, family therapy, fluoxetine (alone or with cognitive therapy or CBT), fluvoxamine, group therapeutic support (other than CBT), guided self-help, individual psychodynamic psychotherapy, interpersonal therapy, lithium, mirtazapine, monoamine oxidase inhibitors (MAOIs), omega-3 polyunsaturated fatty acids, paroxetine, sertraline (alone or with CBT), St John's Wort (Hypericum perforatum), tricyclic antidepressants, and venlafaxine.
Topics: Adolescent; Antidepressive Agents; Anxiety; Child; Cognitive Behavioral Therapy; Depression; Depressive Disorder, Treatment-Resistant; Dopamine Uptake Inhibitors; Excitatory Amino Acid Antagonists; Humans; Psychotherapy, Psychodynamic; Sexual Maturation; Stress, Psychological
PubMed: 22018419
DOI: No ID Found -
Life (Basel, Switzerland) Apr 2023Pramipexole is a dopamine full agonist approved for the treatment of Parkinson's disease and restless legs syndrome. Its high affinity for the D3 receptor and... (Review)
Review
BACKGROUND
Pramipexole is a dopamine full agonist approved for the treatment of Parkinson's disease and restless legs syndrome. Its high affinity for the D3 receptor and neuroprotective, antioxidant, and anti-inflammatory activity provides a rationale for the treatment of depression. In this paper, we review studies on the effectiveness and safety of antidepressant pramipexole augmentation in treatment-resistant depression.
METHODS
This comprehensive systematic review and meta-analysis of observational studies on pramipexole-antidepressant augmentation included patients with resistant unipolar and bipolar depression. The primary outcome measure was the treatment response, measured at the study endpoint.
RESULTS
We identified 8 studies including 281 patients overall, 57% women and 39.5% with bipolar disorder and 60.5% with major depressive disorder. The mean follow-up duration was 27.3 weeks (range 8-69). The pooled estimate of treatment response was 62.5%, without significant differences between unipolar and bipolar depression. Safety was good, with nausea and somnolence the most frequent side effects.
CONCLUSIONS
The findings of this systematic review, needing further confirmation, show that off-label use of pramipexole as augmentation of antidepressant treatment could be a useful and safe strategy for unipolar and bipolar treatment-resistant depression.
PubMed: 37109571
DOI: 10.3390/life13041043