Effects of droxidopa: A Synthesis of Findings from 26 Studies

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Original Abstract of the Article

Major Research Findings

Droxidopa is a medication that has shown promise in treating neurogenic orthostatic hypotension (nOH). nOH is a condition where blood pressure drops significantly when standing up, causing dizziness, lightheadedness, and fainting. Droxidopa is a precursor to norepinephrine, a neurotransmitter that helps regulate blood pressure. Studies have shown that droxidopa can increase blood pressure and improve symptoms in patients with nOH. 4 Droxidopa is converted to norepinephrine in the kidneys, and this conversion is believed to be a key factor in its effectiveness. 4 Clinical trials have confirmed that droxidopa can effectively increase blood pressure and improve symptoms in nOH patients. However, it's important to note that droxidopa can also cause an increase in blood pressure at night. 1 This nighttime increase in blood pressure could potentially put additional strain on the heart, so it's something to be mindful of.

Benefits and Risks

Benefits Summary

Droxidopa has the potential to improve symptoms of nOH. It's expected to increase blood pressure in nOH patients and alleviate symptoms like dizziness, lightheadedness, and fainting. 4 Droxidopa could also contribute to an improved quality of life for nOH patients. 10 It has shown effectiveness even in patients who haven't responded well to other treatment options. 7

Risks Summary

Droxidopa can cause an increase in blood pressure at night. 1 This nighttime blood pressure increase can put extra strain on the heart, so careful monitoring is necessary. Droxidopa can also interact with other medications. 18 It's crucial to take droxidopa as prescribed by a doctor and to be aware of potential interactions.

Comparison Between Studies

Commonalities Among Studies

Many research studies have indicated that droxidopa can increase blood pressure and improve symptoms in nOH patients. 4 19 24 These studies suggest that droxidopa is a promising treatment option for nOH.

Differences Among Studies

The blood pressure increase produced by droxidopa can vary between patients. 24 The dosage and method of administration can also influence the effectiveness of droxidopa.

Consistency and Contradictions in Results

While droxidopa is believed to improve nOH symptoms, it's important to note that it might not be effective for all patients. 6 The exact mechanism by which droxidopa works is not fully understood. 4 Further research is needed to gain a more comprehensive understanding of its effectiveness and safety.

Considerations for Real-World Applications

Although droxidopa holds promise in treating nOH symptoms, it's essential to remember that it may not be effective for all individuals. Always follow a doctor's instructions carefully when taking droxidopa, and be aware of the potential for nighttime blood pressure increases. Since nOH treatment can vary depending on the patient, open communication with your doctor is crucial to finding the right approach.

Limitations of Current Research

There is still a need for more extensive research on droxidopa. Large-scale clinical trials are necessary to gain a more in-depth understanding of its effectiveness and safety. Additional studies are also needed to investigate the impact of droxidopa on nighttime blood pressure levels.

Future Research Directions

Large-scale clinical trials are needed to further evaluate the effectiveness of droxidopa. Research should also focus on understanding the effects of droxidopa on nighttime blood pressure. 24 More research is necessary to gain a deeper understanding of the mechanisms by which droxidopa works. 4

Conclusion

Droxidopa shows potential as a treatment for nOH, but it's crucial to acknowledge its potential side effects. Always follow your doctor's instructions carefully when taking this medication, and be mindful of potential interactions with other medications. It's important to remember that nOH treatment can vary from person to person. Communication with your doctor is key in finding the right treatment approach for your individual needs.

Literature analysis of 26 papers
Positive Content
22
Neutral Content
1
Negative Content
3
Article Type
4
1
1
3
26
1.

Effects of the novel norepinephrine prodrug, droxidopa, on ambulatory blood pressure in patients with neurogenic orthostatic hypotension.

Author: KaufmannHoracio, Norcliffe-KaufmannLucy, HewittL Arthur, RowseGerald J, WhiteWilliam B

Orthostatic hypotension treatment
Hypertension

The prodrug droxidopa increases blood pressure (BP) in patients with neurogenic orthostatic hypotension. This study investigated the BP profile of droxidopa using ambulatory BP monitoring. These data demonstrate that ambulatory BP monitoring is useful to evaluate the circadian BP profile after initiating treatment with a pressor agent.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

Ipilimumab-induced Guillain-Barré Syndrome Presenting as Dysautonomia: An Unusual Presentation of a Rare Complication of Immunotherapy.

Author: Kelly WuW, BromanKristy K, BrownieEvan R, KauffmannRondi M

Guillain-Barré syndrome
Neurological complications
Pandysautonomia

This case report describes a patient who developed pandysautonomia and Guillain-Barré syndrome after receiving a single dose of ipilimumab for resected stage III melanoma. The authors emphasize the importance of awareness and recognition of the potential for profound immune-mediated adverse effects associated with ipilimumab treatment.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

3.

Droxidopa, an oral norepinephrine precursor, improves hemodynamic and renal alterations of portal hypertensive rats.

Author: CollMar, RodriguezSarai, RaurellImma, EzkurdiaNahia, BrullAstrid, AugustinSalvador, GuardiaJaime, EstebanRafael, MartellMaría, GenescàJoan

Portal hypertension treatment

This study investigated the effects of droxidopa, a medication used to treat low blood pressure, on hemodynamic and renal function in rats with portal hypertension, a condition that occurs when blood pressure in the portal vein is elevated. Droxidopa was found to improve hemodynamic parameters and increase urine production in rats with portal hypertension. The study suggests that droxidopa may be a beneficial treatment for portal hypertension, but further research is needed.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

Substantial renal conversion of L-threo-3,4-dihydroxyphenylserine (droxidopa) to norepinephrine in patients with neurogenic orthostatic hypotension.

Author: LamotteGuillaume, HolmesCourtney, SullivanPatti, GoldsteinDavid S

Treats orthostatic hypotension

Droxidopa, a drug for low blood pressure, increases norepinephrine levels in the kidneys, which may contribute to its effectiveness.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., IntramuralFunding provided by the NIH for research projects within the NIH.

Language : English

5.

Gata3 loss leads to embryonic lethality due to noradrenaline deficiency of the sympathetic nervous system.

Author: LimK C, LakshmananG, CrawfordS E, GuY, GrosveldF, EngelJ D

Improved SNS function
Embryonic lethality
Neural crest defects
Renal hypoplasia

Gata3 deficiency in mouse embryos leads to reduced noradrenaline in the sympathetic nervous system (SNS), which is a proximal cause of death.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

6.

Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa.

Author: BiaggioniItalo, FreemanRoy, MathiasChristopher J, LowPhillip, HewittL Arthur, KaufmannHoracio,

Neurogenic orthostatic hypotension treatment

This study evaluated the effectiveness of droxidopa for treating symptomatic neurogenic orthostatic hypotension (OH). Droxidopa failed to meet the primary efficacy endpoint of improving dizziness/lightheadedness, but showed positive secondary outcomes, suggesting that additional clinical trials are needed to confirm its benefits for symptomatic neurogenic OH.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

L-DOPS therapy for refractory orthostatic hypotension in autoimmune autonomic neuropathy.

Author: GibbonsChristopher H, VerninoSteven A, KaufmannHoracio, FreemanRoy

Improved blood pressure
Orthostatic tolerance

A 46-year-old woman with antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia experienced severe orthostatic intolerance. L-DOPS significantly improved blood pressure and orthostatic tolerance.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

9.

Development and validation of a UPLC-MS/MS method for quantitation of droxidopa in human plasma: Application to a pharmacokinetic study.

Author: WangHaidong, YangGuangsheng, ZhouJinyu, PeiJiang, ZhangQiangfeng, SongXingfa, SunZengxian

Quantify droxidopa in human plasma

This study developed and validated a simple and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantifying droxidopa in human plasma. The method was successfully applied to a pharmacokinetic study of droxidopa in healthy Chinese volunteers.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Validation StudyResearch to assess the validity and reliability of new measurement methods or diagnostic tests.

Language : English

10.

Orthostatic hypotension in hereditary transthyretin amyloidosis: epidemiology, diagnosis and management.

Author: PalmaJose-Alberto, Gonzalez-DuarteAlejandra, KaufmannHoracio

Neurogenic orthostatic hypotension treatment
Quality of life improvement
TTR amyloidosis treatment

Neurogenic orthostatic hypotension, which affects an estimated 40-60% of patients with hereditary transthyretin (TTR) amyloidosis, can be treated with non-pharmacologic and pharmacologic strategies.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

11.

Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial.

Author: KaufmannHoracio, VickeryRoss, WangWhedy, KanodiaJitendra, ShibaoCyndya A, Norcliffe-KaufmannLucy, HaumannBrett, BiaggioniItalo

Ampreloxetine
Neurogenic orthostatic hypotension treatment

This study explores the safety and efficacy of ampreloxetine, a selective norepinephrine reuptake inhibitor, for treating neurogenic orthostatic hypotension (nOH). The study found that ampreloxetine was generally well-tolerated and resulted in improvements in blood pressure and symptoms in patients with nOH.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

L-threo-dihydroxyphenylserine corrects neurochemical abnormalities in a Menkes disease mouse model.

Author: DonsanteAnthony, SullivanPatricia, GoldsteinDavid S, BrinsterLauren R, KalerStephen G

Improved brain neurochemicals

This study investigated the effects of L-DOPS on brain neurochemical abnormalities and neuropathology in a mouse model of Menkes disease.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., IntramuralFunding provided by the NIH for research projects within the NIH.

Language : English

13.

Managing autonomic dysfunction in Parkinson's disease: a review of emerging drugs.

Author: KulshreshthaDinkar, GangulyJacky, JogMandar

Bladder dysfunction treatment
Constipation management
Orthostatic hypotension management
Sialorrhea management

This review explores the pathophysiology and treatment options for autonomic dysfunction in Parkinson disease (PD).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

14.

Atomoxetine for Orthostatic Hypotension in an Elderly Patient Over 10 Weeks: A Case Report.

Author: HaleGenevieve M, BrennerMichael

Orthostatic hypotension treatment

This report discusses a case of atomoxetine use for 10 weeks in an elderly patient with primary orthostatic hypotension. Atomoxetine was initiated, and the patient showed gradual improvements in symptoms and blood pressure control over the course of 10 weeks. Our data suggest that low-dose atomoxetine is an effective and safe agent for symptom improvement and blood pressure control in elderly patients with primary orthostatic hypotension.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

15.

Supine plasma NE predicts the pressor response to droxidopa in neurogenic orthostatic hypotension.

Author: PalmaJose-Alberto, Norcliffe-KaufmannLucy, MartinezJose, KaufmannHoracio

Improved pressor response
None reported

Lower supine plasma NE levels in patients with neurogenic orthostatic hypotension are associated with a greater pressor effect of droxidopa treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Effects of carbidopa and entacapone on the metabolic fate of the norepinephrine prodrug L-DOPS.

Author: GoldsteinDavid S, HolmesCourtney, SewellLaToya, PechnikSandra, KopinIrwin J

Orthostatic hypotension treatment
Drug interactions
Parkinson's disease

L-DOPS is a prodrug of norepinephrine that is being investigated for orthostatic hypotension. This study found that carbidopa, an inhibitor of L-aromatic amino-acid decarboxylase, blocks the conversion of L-DOPS to norepinephrine and reduces its pressor effect.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., IntramuralFunding provided by the NIH for research projects within the NIH.

Language : English

19.

Safety and Durability of Effect with Long-Term, Open-Label Droxidopa Treatment in Patients with Symptomatic Neurogenic Orthostatic Hypotension (NOH303).

Author: IsaacsonStuart, ShillHolly A, VerninoSteven, ZiemannAdam, RowseGerald J

nOH symptom improvement
Falls
Headache
Urinary tract infection

Long-term, open-label treatment with droxidopa for up to 12 months was generally well tolerated and provided durable improvements in neurogenic orthostatic hypotension (nOH) signs and symptoms.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.

Language : English

20.

Embryonic lethality in mice lacking mismatch-specific thymine DNA glycosylase is partially prevented by DOPS, a precursor of noradrenaline.

Author: SaitoYusuke, OnoTetsuya, TakedaNaoki, NohmiTakehiko, SekiMasayuki, EnomotoTakemi, NodaTetsuo, UeharaYoshihiko

Embryonic survival

Tdg mutant mice died in utero by 11.5 days post coitum (dpc) due to a reduction in noradrenaline levels. The administration of DOPS, a synthetic precursor of noradrenaline, partially rescued the Tdg (-/-) embryos.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

21.

Orthostatic Hypotension in the Hypertensive Patient.

Author: BiaggioniItalo

Fall prevention
Hypertension management
OH treatment
Increased blood pressure

Orthostatic hypotension (OH) is a common medical problem, particularly in older adults with multiple comorbidities and polypharmacy. Management of OH in hypertensive patients is challenging, but a comprehensive approach focusing on drug removal, non-pharmacological interventions, and appropriate pressor agents can be effective.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

22.

Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors.

Author: CryanJohn F, O'LearyOlivia F, JinSung-Ha, FriedlandJulie C, OuyangMing, HirschBradford R, PageMichelle E, DalviAshutosh, ThomasSteven A, LuckiIrwin

Antidepressant effect

This study investigates the role of norepinephrine (NE) in mediating the acute behavioral effects of antidepressants in mice. The research reveals that NE plays a crucial role in the effects of many antidepressants, including most selective serotonin reuptake inhibitors (SSRIs).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

24.

Standing and Supine Blood Pressure Outcomes Associated With Droxidopa and Midodrine in Patients With Neurogenic Orthostatic Hypotension: A Bayesian Meta-analysis and Mixed Treatment Comparison of Randomized Trials.

Author: ChenJack J, HanYi, TangJonathan, PortilloIvan, HauserRobert A, DashtipourKhashayar

Increased SBP
Supine hypertension

Both droxidopa and midodrine were effective in increasing standing systolic blood pressure (sSBP) in patients with neurogenic orthostatic hypotension (NOH), with midodrine producing a greater increase. However, midodrine also significantly increased the risk of supine hypertension.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

25.

DBH deficiency in an elderly patient: efficacy and safety of chronic droxidopa.

Author: DespasFabien, PathakA, BerryM, CagnacR, MassabuauP, LiozonE, GalinierM, SenardJ M

Cardiovascular safety
Sympathetic activity

The effects of chronic droxidopa in a patient with dopamine beta-hydroxylase deficiency were described.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

26.

Hyperinsulinemia and Insulin Resistance in Dopamine β-Hydroxylase Deficiency.

Author: ArnoldAmy C, GarlandEmily M, CeledonioJorge E, RajSatish R, AbumradNaji N, BiaggioniItalo, RobertsonDavid, LutherJames M, ShibaoCyndya A

Hyperinsulinemia
Insulin resistance
Orthostatic hypotension

Dopamine β-hydroxylase (DBH) deficiency is a rare genetic disorder. This study discusses the potential impact of DBH deficiency on glucose homeostasis in humans.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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