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Annales D'endocrinologie Jun 2021The surveillance strategy for patients taking low dose cabergoline for hyperprolactinaemia is controversial. As more evidence has emerged that the risks of cardiac... (Review)
Review
The surveillance strategy for patients taking low dose cabergoline for hyperprolactinaemia is controversial. As more evidence has emerged that the risks of cardiac valvulopathy in this population of patients are low, fewer and fewer endocrinologists adhere strictly to the original medicines and healthcare products agency MHRA guidance of "at least" annual echocardiography. Strict adherence to this guidance would be costly in monetary terms (£5.76 million/year in the UK) and also in resource use (90,000 extra echocardiograms/year). This article reviews the proposed pathophysiological mechanism underlying the phenomenon of dopamine agonist valvulopathy, the characteristic echocardiographic changes seen, summarises the published literature on the incidence of valvulopathy with low dose cabergoline and examines the previous and current evidence-based screening guidelines.
Topics: Cost-Benefit Analysis; Dopamine Agonists; Drug Monitoring; Echocardiography; Heart Valve Diseases; Humans; Hyperprolactinemia; Incidence; Monitoring, Physiologic; United Kingdom
PubMed: 32178837
DOI: 10.1016/j.ando.2020.02.007 -
Perspectives in Psychiatric Care Jul 2017To review the data regarding a new antipsychotic, cariprazine. (Review)
Review
PURPOSE
To review the data regarding a new antipsychotic, cariprazine.
CONCLUSIONS
Cariprazine is a dopamine D3, D2 partial agonist, with greater affinity to D3. It has been examined for schizophrenia, bipolar mania, bipolar depression, and unipolar depression. It has demonstrated efficacy in schizophrenia and mania, and has recently been approved by the U.S. Food and Drug Administration. However, it has a more inconsistent effect in depression, both unipolar and bipolar. Adverse effects include extrapyramidal symptoms, akathisia, and gastrointestinal distress.
PRACTICE IMPLICATIONS
Cariprazine will be a promising addition in the treatment of patients with acute mania and schizophrenia.
Topics: Antipsychotic Agents; Bipolar Disorder; Dopamine Agonists; Humans; Piperazines
PubMed: 27059102
DOI: 10.1111/ppc.12150 -
Psychiatry and Clinical Neurosciences Mar 2023Impulse control disorders (e.g. pathological gambling, hypersexuality) may develop as adverse reactions to drugs. Pathogenetic hypotheses have mainly focused on...
INTRODUCTION
Impulse control disorders (e.g. pathological gambling, hypersexuality) may develop as adverse reactions to drugs. Pathogenetic hypotheses have mainly focused on D3-receptor agonism, and switching to alternatives with different pharmacologic mechanisms represents a common management strategy. Nonetheless, treatment failure is common and gaining pathophysiological insights is needed.
AIM
We aimed to identify targets potentially contributing to pathologic impulsivity.
METHOD
We performed a pharmacovigilance-pharmacodynamic study on dopamine agonists and antipsychotics using the Food and Drug Administration Adverse Event Reporting System (January 2004-December 2021). We estimated disproportionate reporting using the Bayesian information component. Using online public databases (IUPHAR, ChEMBL, PDSP, DrugBank), we calculated drug occupancies. To identify the targets potentially contributing to impulsivity, we fitted univariate regression models interpolating information components and occupancies within dopamine agonists and antipsychotics. Sensitivity analyses were performed to check for the robustness of the results.
RESULTS
Among 19 887 reports of impulsivity, 5898 recorded an antipsychotic, and 3100 a dopamine agonist. The more robust signals concerned aripiprazole (N = 3091; median information component [95% confidence interval] = 4.51[4.45-4.55]) and brexpiprazole (229; 4.00[3.78-4.16]) for antipsychotics, pergolide (105; 5.82[5.50-6.06]) and pramipexole (2009; 5.43[5.36-5.48]) for dopamine agonists. Robust, significant positive associations between drug occupancy and impulsivity reporting were found for D3 within dopamine agonists (beta = 1.52; P-value = 0.047) and 5-HT1a within antipsychotics (1.92, 0.029).
CONCLUSION
Our results supported the role of D3-receptor agonism in inducing impulsivity in dopamine receptor agonists and identified a potential role of 5-HT1a receptor agonism in antipsychotics. Investigating these receptors may drive towards a better management of drug-induced impulsivity.
Topics: Humans; Dopamine Agonists; Antipsychotic Agents; Pharmacovigilance; Bayes Theorem; Disruptive, Impulse Control, and Conduct Disorders
PubMed: 36436204
DOI: 10.1111/pcn.13511 -
Expert Review of Endocrinology &... Nov 2022Treatment of prolactinomas with dopamine agonists has been the established first-line treatment option for many years, with surgery reserved for refractory cases or...
INTRODUCTION
Treatment of prolactinomas with dopamine agonists has been the established first-line treatment option for many years, with surgery reserved for refractory cases or medication intolerance. This approach may not be the best option in many cases.
AREAS COVERED
Review of the epidemiology, biology, and treatment options available for prolactinomas, including best available data on outcomes, costs, and morbidities for each therapy. These data are then used to propose a 'surgery-first' treatment approach for a subset of prolactinomas as an alternative to primary medical management.
EXPERT OPINION
Based on the available data, there is a strong rationale that transsphenoidal surgery should be considered a first-line treatment option for both micro- and macro-prolactinomas that do not demonstrate high grade cavernous sinus invasion on MRI imaging, with dopamine agonists administered as a secondary therapy for tumors not in remission following surgery, and for giant tumors. This 'surgery-first' approach assumes the availability of skilled and experienced pituitary surgeons to ensure optimal outcomes. This approach should result in high cure rates and reduced DA requirements for patients not cured from initial surgery. Further, it will reduce medical costs over a patient's lifetime and the chronic morbidities associated with protracted dopamine agonist usage.
Topics: Humans; Prolactinoma; Dopamine Agonists; Bromocriptine; Pituitary Neoplasms; Magnetic Resonance Imaging
PubMed: 36200144
DOI: 10.1080/17446651.2022.2131531 -
Neuropharmacology Feb 2022Motor complications, characterized by "off" periods - when anti-parkinsonian medications are ineffective - and dyskinesia, are the hallmark of advanced Parkinson's... (Review)
Review
BACKGROUND
Motor complications, characterized by "off" periods - when anti-parkinsonian medications are ineffective - and dyskinesia, are the hallmark of advanced Parkinson's disease (PD). While levodopa is the gold standard PD medication in terms of efficacy, its short duration of effect coupled with progressive loss of dopaminergic neurons leads to motor complications and fails to treat off periods.
PURPOSE OF REVIEW
This review focuses on novel dopaminergic therapies that were recently made clinically available or are currently in development for the treatment of motor complications. First, it will discuss rescue therapies for the treatment of off episodes, including novel apomorphine and levodopa formulations. Second, it will highlight adjunctive dopaminergic medications approved to reduce total daily off time. Third, it will discuss longer-acting levodopa formulations in development and introduce a novel selective dopamine agonist under study. Finally, it will cover novel dopaminergic delivery mechanisms, with specific focus on continuous subcutaneous infusions in development.
SUMMARY
The breadth of dopaminergic therapies recently approved or in development for motor complications, and specifically off time reduction, evokes cautious optimism. Gains in reducing off time with rescue therapies, adjunctive medications or longer-acting levodopa formulations are modest, and underscore the need for more continuous dopaminergic delivery to address the underlying pathophysiology and translate to clinically meaningful improvement in motor complications.
Topics: Alanine; Antiparkinson Agents; Apomorphine; Benzylamines; Delayed-Action Preparations; Disease Progression; Dopamine Agents; Dopamine Agonists; Drug Compounding; Drug Delivery Systems; Dyskinesias; Humans; Levodopa; Oxadiazoles; Parkinson Disease
PubMed: 34742740
DOI: 10.1016/j.neuropharm.2021.108869 -
BMJ Case Reports Feb 2019A 47-year-old Caucasian man was referred to our clinic with a severe clinical and biochemical phenotype of endogenous hypercortisolism for further evaluation and...
A 47-year-old Caucasian man was referred to our clinic with a severe clinical and biochemical phenotype of endogenous hypercortisolism for further evaluation and treatment. In addition to confirming adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, we found left temporal hemianopsia, massively increased prolactin, increased growth hormone/insulin-like growth factor 1 values, hypogonadotropic hypogonadism and central hypothyroidism. As the cause of these abnormalities we revealed an invasive macroadenoma of the pituitary secreting ACTH, prolactin and growth hormone, resulting not only in a clinically predominant picture of Cushing's syndrome but also causing hypogonadotropic hypogonadism and central hypothyroidism. The patient responded surprisingly well to dopamine agonist treatment leading not only to normalisation of prolactin levels but also to clinical and biochemical remission of Cushing's syndrome. Tumour size decreased successively in follow-up MRI scans. Despite lacking immunohistochemical analysis of tumour tissue, we assume plurihormonal secretion of ACTH, prolactin and growth hormone from pituitary macroadenoma, which fortunately responded well to dopamine agonist treatment.
Topics: Adenoma; Adult; Dopamine Agonists; Humans; Male; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Prolactin; Treatment Outcome
PubMed: 30765454
DOI: 10.1136/bcr-2018-228045 -
Reviews on Recent Clinical Trials Jan 2018Schizophrenia is a chronic and debilitating mental disorder that affects the patient's and their family's life. The disease remains a complicated disorder that is... (Review)
Review
BACKGROUND
Schizophrenia is a chronic and debilitating mental disorder that affects the patient's and their family's life. The disease remains a complicated disorder that is challenging to treat, despite there being a large antipsychotic armamentarium. Brexpiprazole acts both as a partial agonist at the serotonin 5-HT1A and dopamine D2 receptors and as an antagonist at the serotonin 5- HT2A and noradrenaline alpha1B and alpha2C receptors, all with similar potency. This balanced receptor profile may produce promising antipsychotic effects on positive, negative and cognitive symptoms in schizophrenia with minimal adverse effects.
METHODS
This review summarizes the pharmacodynamics and pharmacokinetic profile of brexpiprazole and the clinical trial information pertaining to its effectiveness and safety and tolerability, discusses its best clinical use, and compares its clinical profile to those of other widely used antipsychotic agents.
RESULTS
Brexpiprazole demonstrated significant clinical efficacy and had good safety and tolerability in well-designed trials with patients with schizophrenia. This agent may be a useful treatment alternative.
CONCLUSION
However, it will be valuable to consider a long-term observational study that includes an active comparator, especially other second-generation antipsychotics (SGAs), to further evaluate the efficacy and safety of brexpiprazole in the treatment of schizophrenia.
Topics: Dopamine Agonists; Humans; Quinolones; Schizophrenia; Thiophenes; Treatment Outcome
PubMed: 28828976
DOI: 10.2174/1574887112666170821114831 -
Primary Care Diabetes Feb 2016Dopamine action appears to play a role in changes that are seen in obesity, metabolic syndrome and type 2 diabetes mellitus. Bromocriptine-QR (Quick Release), a dopamine... (Review)
Review
Dopamine action appears to play a role in changes that are seen in obesity, metabolic syndrome and type 2 diabetes mellitus. Bromocriptine-QR (Quick Release), a dopamine agonist, is approved for use in treatment of type 2 diabetes. It has demonstrated modest improvement in glycemic parameters, cholesterol and weight in certain cohorts. Limited data using cabergoline, a long-acting dopamine agonist, also demonstrate glycemic efficacy. Additionally, bromocriptine-QR appears to have a favorable cardiovascular risk reduction. The direct mechanism by which bromocriptine-QR, or central dopamine agonism, achieves modest glycemic control and favorable cardio-metabolic profile is unclear. This relationship appears to be more complex than the historical explanation of "resetting" the circadian clock and may further be elucidated using data in individuals with hyperprolactinemia and prolactinoma.
Topics: Animals; Biomarkers; Blood Glucose; Bromocriptine; Cabergoline; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus, Type 2; Dopamine Agonists; Ergolines; Humans; Hypoglycemic Agents; Risk Factors; Treatment Outcome
PubMed: 26670921
DOI: 10.1016/j.pcd.2015.10.008 -
Current Medicinal Chemistry 2016The use of dopaminergic agonists is key in the treatment of Parkinson's disease and related central nervous system (CNS) neurodegenerative disorders. Despite there are a... (Review)
Review
The use of dopaminergic agonists is key in the treatment of Parkinson's disease and related central nervous system (CNS) neurodegenerative disorders. Despite there are a number of commercialized dopaminergic agonists that are currently being used successfully in the first stages of the disease, they often fail to provide sustained clinical benefit for a long period due to the appearance of side-effects such as augmentation, sleepiness, nausea, hypothension, and compulsive behaviors among others. New dopaminergic agonists with less side effects are being developed. These novel compounds offer an alternative when the disease progresses and patients fail to respond to standard dopaminergic treatments or side-effects increased. Chemistry, and in particular chemical synthesis, has played a major role in bringing synthetic dopaminergic agonists to the clinic and continues to be crucial for the development of new and necessary drugs for long-term treatments with less undesired side effects. A number of structural modifications of parent compounds have led to enhanced agonism but also partial agonism or even antagonism of one or more dopamine receptors. In some cases, these activities are accompanied by agonist effect at serotonin receptors which suggests a potential clinical application in the treatment of schizophrenia In this review, chemical synthesis of dopaminergic agents, their affinity, and the corresponding agonist/antagonist effects will be highlighted.
Topics: Apomorphine; Dopamine Agonists; Drug Design; Humans; Indoles; Parkinson Disease; Phenanthridines; Quinolines; Receptors, Dopamine
PubMed: 27142290
DOI: 10.2174/0929867323666160504103621 -
CNS Drugs May 2020Aripiprazole, brexpiprazole and cariprazine differ from all other second-generation antipsychotics due to partial agonism at the dopamine D2 and D3 receptors. In... (Comparative Study)
Comparative Study Review
Aripiprazole, brexpiprazole and cariprazine differ from all other second-generation antipsychotics due to partial agonism at the dopamine D2 and D3 receptors. In contrast to aripiprazole, brexpiprazole has lower intrinsic dopamine D2 activity and higher affinity for the serotonin 5-HT1A and 5-HT2A receptors, while cariprazine has the highest affinity for the dopamine D3 receptor, and the longest half-life. The main adverse effect of dopamine receptor partial agonists (DRPAs) is akathisia of low-to-moderate severity, which occurs in a small proportion of patients, usually in the first few weeks of treatment. While definitive conclusions concerning differences between the DRPAs require head-to-head comparison studies, on the available evidence, akathisia is probably least likely to occur with brexpiprazole and most likely with cariprazine; the risk of akathisia with aripiprazole lies in between. Weight-gain risk is low with aripiprazole and cariprazine, but moderate with brexpiprazole. Risk of sedation is low with DRPAs, as is risk of insomnia and nausea. Partial dopamine agonism leads to a low risk for hyperprolactinaemia (and probably a low risk of sexual dysfunction). Prolactin concentrations fall in some patients (particularly those with elevated levels prior to initiating the drugs). Rates of discontinuation due to adverse effects in pivotal studies were low, and on the whole, DRPAs are well tolerated. Aripiprazole has been implicated in pathological gambling and other impulse control behaviours, likely due to partial dopamine agonist activity (there have been no reports with brexpiprazole and cariprazine). The risks for diabetes and tardive dyskinesia with DRPAs are unknown, but are likely to be low. On the basis of tolerability, DRPAs should be considered as first-line treatment options, particularly in patients with early schizophrenia.
Topics: Animals; Antipsychotic Agents; Aripiprazole; Dopamine Agonists; Humans; Piperazines; Quinolones; Receptors, Dopamine D2; Receptors, Dopamine D3; Schizophrenia; Thiophenes
PubMed: 32246399
DOI: 10.1007/s40263-020-00718-4