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Therapeutic Advances in... 2022Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and... (Review)
Review
BACKGROUND
Clozapine is the most effective medication for treatment-refractory schizophrenia but is associated with significant adverse drug effects, including hypotension and dizziness, which have a negative impact on quality of life and treatment compliance. Available evidence for the management of clozapine-induced hypotension is scant.
OBJECTIVES
Due to limited guidance on the safety and efficacy of pharmacological treatments for clozapine-induced hypotension, we set out to systematically review and assess the evidence for the management of clozapine-induced hypotension and provide guidance to clinicians, patients, and carers.
DESIGN
We undertook a systematic review of the safety and efficacy of interventions for clozapine-induced hypotension given the limited available evidence.
DATA SOURCES AND METHODS
PubMed, Embase, PsycINFO, CINAHL, and the Cochrane trial Registry were searched from inception to November 2021 for literature on the treatment strategies for clozapine-induced hypotension and dizziness using a PROSPERO pre-registered search strategy. For orthostatic hypotension, we developed a management framework to assist in the choice of intervention.
RESULTS
We identified nine case studies and four case series describing interventions in 15 patients. Hypotension interventions included temporary clozapine dose reduction, non-pharmacological treatments, and pharmacological treatments. Midodrine, fludrocortisone, moclobemide and Bovril combination, and etilefrine were associated with improvement in symptoms or reduction in orthostatic hypotension. Angiotensin II, arginine vasopressin, and noradrenaline successfully restored and maintained mean arterial pressure in critical care situations. A paradoxical reaction of severe hypotension was reported with adrenaline use.
CONCLUSION
Orthostatic hypotension is a common side effect during clozapine titration. Following an assessment of the titration schedule, salt and fluid intake, and review of hypertensive and nonselective α1-adrenergic agents, first-line treatment should be a temporary reduction in clozapine dose or non-pharmacological interventions. If orthostatic hypotension persists, fludrocortisone should be trialled with monitoring of potassium levels and sodium and fluid intake. Midodrine may be considered second-line or where fludrocortisone is contraindicated or poorly tolerated. For patients on clozapine with hypotension in critical care settings, the use of adrenaline to maintain mean arterial pressure should be avoided.
REGISTRATION
PROSPERO (Registration No. CRD42020191530).
PubMed: 35633931
DOI: 10.1177/20451253221092931 -
Australian Prescriber Feb 2021
Review
PubMed: 33664549
DOI: 10.18773/austprescr.2020.081 -
Journal of General Internal Medicine Nov 2013To perform a systematic review and meta-analysis of clinical trials evaluating the efficacy and safety of midodrine in orthostatic hypotension (OH). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To perform a systematic review and meta-analysis of clinical trials evaluating the efficacy and safety of midodrine in orthostatic hypotension (OH).
METHODS
We searched major databases and related conference proceedings through June 30, 2012. Two reviewers independently selected studies and extracted data. Random-effects meta-analysis was used to pool the outcome measures across studies.
RESULTS
Seven trials were included in the efficacy analysis (enrolling 325 patients, mean age 53 years) and two additional trials were included in the safety analysis. Compared to placebo, the mean change in systolic blood pressure was 4.9 mmHg (p = 0.65) and the mean change in mean arterial pressure from supine to standing was -1.7 mmHg (p = 0.45). The change in standing systolic blood pressure before and after giving midodrine was 21.5 mmHg (p < 0.001). A significant improvement was seen in patients' and investigators' global assessment symptoms scale (a mean difference of 0.70 [95 % CI 0.30-1.09; p < 0.001] and 0.80 [95 % CI 0.76-0.85; p < 0.001], respectively). There was a significant increase in risk of piloerection, scalp pruritis, urinary hesitancy/retention, supine hypertension and scalp paresthesia after giving midodrine. The quality of evidence was limited by imprecision, heterogeneity and increased risk of bias.
CONCLUSION
There is insufficient and low quality evidence to support the use of midodrine for OH.
Topics: Blood Pressure; Clinical Trials as Topic; Humans; Hypotension, Orthostatic; Midodrine; Vasoconstrictor Agents
PubMed: 23775146
DOI: 10.1007/s11606-013-2520-3 -
Annals of Hepatology 2019Hepatorenal syndrome has the worst prognosis among causes of acute kidney injury in cirrhotic patients. Its definitive treatment is liver transplantation. Nevertheless,... (Review)
Review
Hepatorenal syndrome has the worst prognosis among causes of acute kidney injury in cirrhotic patients. Its definitive treatment is liver transplantation. Nevertheless, considering its high short-term mortality rate and the shortage of liver grafts, a pharmacological treatment is of utmost importance, serving as a bridge to liver transplant. The clinical management of hepatorenal syndrome is currently based on the use of a vasoconstrictor in association with albumin. Terlipressin, noradrenaline and the combination of midodrine and octreotide could be used to treat hepatorenal syndrome. Among these options, terlipressin seems to gather the strongest body of evidence regarding efficacy and should be considered the first line of treatment whenever available and in the absence of contraindications. Treatment with a vasoconstrictor and albumin should be promptly initiated after the diagnosis of hepatorenal syndrome in order for patients to have higher chances of recovery.
Topics: Acute Kidney Injury; Albumins; Animals; Hepatorenal Syndrome; Humans; Liver Cirrhosis; Splanchnic Circulation; Treatment Outcome; Vasoconstriction; Vasoconstrictor Agents; Vasodilation
PubMed: 31023616
DOI: 10.1016/j.aohep.2018.12.002 -
Current Hypertension Reports Aug 2013Orthostatic hypotension is a condition commonly affecting the elderly and is often accompanied by disabling presyncopal symptoms, syncope and impaired quality of life.... (Review)
Review
Orthostatic hypotension is a condition commonly affecting the elderly and is often accompanied by disabling presyncopal symptoms, syncope and impaired quality of life. The pathophysiology of orthostatic hypotension is linked to abnormal blood pressure regulatory mechanisms and autonomic insufficiency. As part of its diagnostic evaluation, a comprehensive history and medical examination focused on detecting symptoms and physical findings of autonomic neuropathy should be performed. In individuals with substantial falls in blood pressure upon standing, autonomic function tests are recommended to detect impairment of autonomic reflexes. Treatment should always follow a stepwise approach with initial use of nonpharmacologic interventions including avoidance of hypotensive medications, high-salt diet and physical counter maneuvers. If these measures are not sufficient, medications such as fludrocortisone and midodrine can be added. The goals of treatment are to improve symptoms and to make the patient as ambulatory as possible instead of targeting arbitrary blood pressure values.
Topics: Aging; Blood Pressure; Blood Pressure Determination; Humans; Hypertension; Hypotension, Orthostatic; Syncope
PubMed: 23832761
DOI: 10.1007/s11906-013-0362-3 -
Clinical Gastroenterology and... Sep 2023Hepatorenal syndrome (HRS) can occur in patients with cirrhosis and ascites due to splanchnic vasodilation, renal hypoperfusion, and vasoconstriction. HRS is a diagnosis... (Review)
Review
BACKGROUND & AIMS
Hepatorenal syndrome (HRS) can occur in patients with cirrhosis and ascites due to splanchnic vasodilation, renal hypoperfusion, and vasoconstriction. HRS is a diagnosis of exclusion and portends a poor prognosis, with upward of 80% mortality at 2 weeks without treatment. This review will highlight randomized controlled trials for HRS pharmacotherapy.
METHODS
A PubMed review of randomized controlled trials conducted over the past 25 years was undertaken; 18 studies were included.
RESULTS
Initial studies showed that norepinephrine is as effective as terlipressin for HRS reversal. Midodrine with octreotide and albumin is less effective than terlipressin but better than albumin alone at improving 30-day mortality. Recently, terlipressin with albumin led to significantly higher rates of HRS reversal compared to albumin alone. Non-response to terlipressin can predict 90-day mortality in acute-on-chronic-liver failure.
CONCLUSIONS
Our current understanding of HRS treatment is improved by recent randomized clinical trials. Previous studies using varying medication doses along with the "old" definition of hepatorenal syndrome (HRS type 1) rather than HRS-AKI means that there is still a need for future multicenter prospective studies further refining the risk-benefit ratio of vasoconstrictors for HRS-AKI patients. The Food and Drug Administration has approved terlipressin for use in September 2022. Because it will take time to adapt into clinical practice, less cost-prohibitive vasoconstrictors should still be considered. Opportunities also exist to clarify the safety, timing of initiation, as well as possible discontinuation of terlipressin.
Topics: United States; Humans; Hepatorenal Syndrome; Terlipressin; Prospective Studies; Acute Kidney Injury; Vasoconstrictor Agents; Albumins; Multicenter Studies as Topic
PubMed: 37625864
DOI: 10.1016/j.cgh.2023.06.006 -
Cureus Feb 2024Sepsis and septic shock represent critical conditions, often necessitating vasopressor support in the intensive care unit (ICU). Midodrine, an oral vasopressor, has... (Review)
Review
Sepsis and septic shock represent critical conditions, often necessitating vasopressor support in the intensive care unit (ICU). Midodrine, an oral vasopressor, has gathered attention as a potential adjunct to vasopressor therapy, aiming to facilitate weaning and improve clinical outcomes. However, the efficacy of midodrine remains questionable, with conflicting evidence from clinical trials and meta-analyses. This article provides a comprehensive review of the literature on midodrine's role in ICU settings by gathering evidence from multicenter trials, retrospective studies, and meta-analyses. While some studies suggest a limited benefit of midodrine in expediting vasopressor weaning and reducing ICU/hospital stays, others report potential advantages, particularly in reducing mortality rates among septic shock patients. Ongoing efforts aim to address knowledge gaps surrounding midodrine's efficacy and safety.
PubMed: 38558716
DOI: 10.7759/cureus.55192 -
Cureus May 2023The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate... (Review)
Review
The literature on pharmacologic treatments for postural orthostatic tachycardia syndrome (POTS) is inconsistent and unstandardized. Therefore, we aimed to evaluate choices in pharmacologic treatment options for POTS and the challenges encountered in the studies. We searched numerous databases like PubMed, Scopus, Embase, Web of Science, and Google Scholar for literature published before April 8, 2023. The search was done to retrieve potential peer-reviewed articles that explored drug therapy in POTS. Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were used to conduct the systematic review. Of the 421 potential articles assessed, 17 met the inclusion criteria. Results demonstrated that pharmacologic treatment options for POTS were effective in reducing symptoms of POTS, but most of the studies were underpowered. Several were terminated due to various reasons. Midodrine ivabradine, bisoprolol, fludrocortisone, droxidopa, desmopressin, propranolol, modafinil, methylphenidate, and melatonin have been studied with positive impact but sample sizes that were low in the range of 10-50 subjects. Therefore, we concluded the treatment options effectively improve symptoms of POTS and increase orthostatic tolerance, but more evidence is needed as most studies had a low sample size and thus are underpowered.
PubMed: 37313107
DOI: 10.7759/cureus.38887 -
The American Journal of Managed Care Oct 2015Neurogenic orthostatic hypotension (NOH) is an orphan disease that primarily affects patients with neurodegenerative disorders such as Parkinson's disease and multiple... (Review)
Review
Neurogenic orthostatic hypotension (NOH) is an orphan disease that primarily affects patients with neurodegenerative disorders such as Parkinson's disease and multiple system atrophy. The first step in the management of NOH is to discontinue or minimize the use of drugs that lower blood pressure. Nonpharmacologic therapy for NOH includes physical countermaneuvers, compression abdominal binders and lower extremity stockings, recognition and avoidance of orthostatic stressors, hydration, and salt supplementation. The management of NOH should also include interventions to prevent falls. Pharmacotherapy for NOH includes the mineralocorticoid drug fludrocortisone to expand plasma volume and the sympathomimetic drugs midodrine and droxidopa. Clinical efficacy, tolerability, and the role of each drug in the treatment paradigm are reviewed here.
Topics: Accidental Falls; Humans; Hypotension, Orthostatic; Neurodegenerative Diseases; Patient Education as Topic; Quality of Life; Sympathomimetics; Syncope
PubMed: 26790110
DOI: No ID Found