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The Journal of Clinical Endocrinology... Nov 2023To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas.
PURPOSE
To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas.
METHODS
Register-based study of patients with giant prolactinomas [serum prolactin (PRL) > 1000 µg/L, tumor diameter ≥40 mm] identified in the Swedish Pituitary Register 1991-2018.
RESULTS
Eighty-four patients [mean age 47 (SD ±16) years, 89% men] were included in the study. At diagnosis, the median PRL was 6305 µg/L (range 1450-253 000), the median tumor diameter was 47 mm (range 40-85), 84% of the patients had hypogonadotropic hypogonadism, and 71% visual field defects. All patients were treated with a dopamine agonist (DA) at some point. Twenty-three (27%) received 1 or more additional therapies, including surgery (n = 19), radiotherapy (n = 6), other medical treatments (n = 4), and chemotherapy (n = 2). Ki-67 was ≥10% in 4/14 tumors. At the last follow-up [median 9 years (interquartile range (IQR) 4-15)], the median PRL was 12 µg/L (IQR 4-126), and the median tumor diameter was 22 mm (IQR 3-40). Normalized PRL was achieved in 55%, significant tumor reduction in 69%, and combined response (normalized PRL and significant tumor reduction) in 43%. In the primary DA-treated patients (n = 79), the reduction in PRL or tumor size after the first year predicted the combined response at the last follow-up (P < .001 and P = .012, respectively).
CONCLUSION
DAs effectively reduced PRL and tumor size, but approximately 1 patient out of 4 needed multimodal treatment. Our results suggest that the response to DA after 1 year is useful for identifying patients who need more careful monitoring and, in some cases, additional treatment.
Topics: Male; Humans; Middle Aged; Female; Prolactinoma; Pituitary Neoplasms; Follow-Up Studies; Sweden; Prolactin; Dopamine Agonists
PubMed: 37403202
DOI: 10.1210/clinem/dgad393 -
Scientific Reports Jan 2022The posterior pallial amygdala (PoA) is located on the basolateral caudal telencephalon, including the basal division of PoA (PoAb) and the compact division of PoA...
The posterior pallial amygdala (PoA) is located on the basolateral caudal telencephalon, including the basal division of PoA (PoAb) and the compact division of PoA (PoAc). PoA plays a vital role in emotion regulation and is considered a part of the amygdala in birds. However, the regulatory functions responsible for motor behaviors and emotions between PoAb and PoAc are poorly understood. Therefore, we studied the structure and function of PoA by tract-tracing methods, constant current electrical stimulation, and different dopamine receptor drug injections in pigeons (Columba livia domestica). PoAb connects reciprocally with two nuclear groups in the cerebrum: 1) a continuum comprising the temporo-parieto-occipitalis, corticoidea dorsolateralis, hippocampus, and parahippocampalis areas and 2) rostral areas of the hemisphere, including the nucleus septalis lateralis and nucleus taeniae amygdalae. Extratelencephalic projections of PoAb terminate in the lateral hypothalamic nucleus and are scattered in many limbic midbrain regions. PoAb and PoAc mainly mediated the turning movement. In the 'open-field' test, D1 agonist and D2 antagonist could significantly reduce the latency period for entering into the central area and increase the residence time in the central area, whereas D1 antagonist and D2 agonist had the opposite effect. PoAb and PoAc are important brain areas that mediate turning behavior.
Topics: Amygdala; Animals; Behavior, Animal; Columbidae; Dopamine; Dopamine Agonists; Dopamine Antagonists; Dopaminergic Neurons; Electric Stimulation; Female; Male; Motor Activity; Neuroanatomical Tract-Tracing Techniques; Open Field Test; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 35013368
DOI: 10.1038/s41598-021-03876-7 -
Progress in Neuro-psychopharmacology &... Aug 2020Addictions involve a spectrum of behaviors that encompass features of impulsivity and compulsivity, herein referred to as impulsive-compulsive spectrum disorders... (Review)
Review
Addictions involve a spectrum of behaviors that encompass features of impulsivity and compulsivity, herein referred to as impulsive-compulsive spectrum disorders (ICSDs). The etiology of ICSDs likely involves a complex interplay among neurobiological, psychological and social risk factors. Neurobiological risk factors include the status of the neuroanatomical circuits that govern ICSDs. These circuits can be altered by disease, as well as exogenous influences such as centrally-acting pharmacologics. The 'poster child' for this scenario is Parkinson's disease (PD) medically managed by pharmacological treatments. PD is a progressive neurodegenerative disease that involves a gradual loss of dopaminergic neurons largely within nigrostriatal projections. Replacement therapy includes dopamine receptor agonists that directly activate postsynaptic dopamine receptors (bypassing the requirement for functioning presynaptic terminals). Some clinically useful dopamine agonists, e.g., pramipexole and ropinirole, exhibit high affinity for the D2/D3 receptor subtypes. These agonists provide excellent relief from PD motor symptoms, but some patients exhibit debilitating ICSD. Teasing out the neuropsychiatric contribution of PD-associated pathology from the drugs used to treat PD motor symptoms is challenging. In this review, we posit that modern clinical and preclinical research converge on the conclusion that dopamine replacement therapy can mediate addictions in PD and other neurological disorders. We provide five categories of evidences that align with this position: (i) ICSD prevalence is greater with D2/D3 receptor agonist therapy vs PD alone. (ii) Capacity of dopamine replacement therapy to produce addiction-like behaviors is independent of disease for which the therapy is being provided. (iii) ICSD-like behaviors are recapitulated in laboratory rats with and without PD-like pathology. (iv) Behavioral pathology co-varies with drug exposure. (v) ICSD Features of ICSDs are consistent with agonist pharmacology and neuroanatomical substrates of addictions. Considering the underpinnings of ICSDs in PD should not only help therapeutic decision-making in neurological disorders, but also apprise ICSDs in general.
Topics: Animals; Behavior, Addictive; Dopamine; Dopamine Agonists; Humans; Parkinson Disease; Receptors, Dopamine D2; Receptors, Dopamine D3
PubMed: 32272129
DOI: 10.1016/j.pnpbp.2020.109942 -
The European Journal of Neuroscience Aug 2019Impulsive-compulsive spectrum disorders are associated with dopamine agonist therapy in some patients. These untoward outcomes occur with direct-acting, full and partial... (Review)
Review
Impulsive-compulsive spectrum disorders are associated with dopamine agonist therapy in some patients. These untoward outcomes occur with direct-acting, full and partial agonists at D2 dopamine family receptors. The disorders typically emerge during chronic treatment, and exhibit common features that are independent of the neurological or psychiatric pathology for which the initial therapy was indicated. It is well-documented that the brain is 'plastic', changing in response to alterations to internal factors (e.g., disease processes), as well as external factors (e.g., therapies). The complexities of these clinical scenarios have eluded a clear depiction of the neurobiology for impulsive-compulsive spectrum disorders and engendered considerable debate regarding the mechanistic underpinnings of the disorders. In this opinion, we use pharmacological concepts related to homeostatic compensation subsequent to chronic receptor activation to provide a unifying construct. This construct helps explain the occurrence of impulsive-compulsive spectrum disorders across disease states, and during therapy with full and partial agonists.
Topics: Animals; Compulsive Behavior; Dopamine; Dopamine Agonists; Dopaminergic Neurons; Humans; Impulsive Behavior; Parkinson Disease; Receptors, Dopamine D2
PubMed: 30269390
DOI: 10.1111/ejn.14177 -
Neurotherapeutics : the Journal of the... Oct 2020Parkinson disease (PD), as a slowly progressive neurodegenerative disorder, undergoes six neuropathological stages. The earliest clinical manifestation presents in the... (Review)
Review
Parkinson disease (PD), as a slowly progressive neurodegenerative disorder, undergoes six neuropathological stages. The earliest clinical manifestation presents in the middle stage of the disorder pathologically, when 50% or more of the dopaminergic neurons have degenerated in the substantia nigra. This discrepancy between the early stage clinically and that pathologically has, in part, spurred the debate as to when it is best to initiate symptomatic therapy. The most well-studied monotherapeutic agents for PD in its early course include levodopa (the cornerstone of PD therapy), dopamine agonists, and monoamine oxidase inhibitors (MAOIs). With several options for initiating pharmacologic therapy, along with the heterogenous presentation of the disorder, an individualized approach is warranted. Careful deliberation must be done to optimize risk reduction while providing effective symptom control, taking the chronological age, comorbidities, social and financial disposition, work status, and both immediate- and long-term goals into consideration. Generally, treatment can be delayed in patients with mild symptoms and minimal functional impairment at any age. If treatment must be initiated, dopamine agonists and monoamine oxidase type B inhibitors can be used, especially in younger patients with milder disease. However, for older patients, those with moderate to severe PD symptoms, regardless of age, or for patients with greater comorbidities, levodopa generally remains the better choice. Eventually, regardless of initial therapy, studies have shown that most will eventually require levodopa therapy when symptoms become more disabling.
Topics: Antiparkinson Agents; Dopamine Agonists; Early Diagnosis; Humans; Levodopa; Monoamine Oxidase Inhibitors; Parkinson Disease; Treatment Outcome
PubMed: 32935299
DOI: 10.1007/s13311-020-00924-4 -
Movement Disorders : Official Journal... Mar 2021No clinical trials have been specifically designed to compare medical treatments after surgery in Parkinson's disease (PD). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
No clinical trials have been specifically designed to compare medical treatments after surgery in Parkinson's disease (PD).
OBJECTIVE
Study's objective was to compare the efficacy and safety of levodopa versus dopamine agonist monotherapy after deep brain stimulation (DBS) in PD.
METHODS
Thirty-five surgical candidates were randomly assigned to receive postoperative monotherapy with either levodopa or dopamine agonist in a randomized, single-blind study. All patients were reevaluated in short- (3 months), mid- (6 months), and long-term (2.5 years) follow-up after surgery. The primary outcome measure was the change in the Non-Motor Symptoms Scale (NMSS) 3 months after surgery. Secondary outcome measures were the percentage of patients maintaining monotherapy, change in motor symptoms, and specific non-motor symptoms (NMS). Analysis was performed primarily in the intention-to-treat population.
RESULTS
Randomization did not significantly affect the primary outcome (difference in NMSS between treatment groups was 4.88 [95% confidence interval: -11.78-21.53, P = 0.566]). In short- and mid-term follow-up, monotherapy was safe and feasible in more than half of patients (60% in short- and 51.5% in mid-term follow-up), but it was more often possible for patients on levodopa. The ability to maintain dopamine agonist monotherapy was related to optimal contact location. In the long term, levodopa monotherapy was feasible only in a minority of patients (34.2%), whereas dopamine agonist monotherapy was not tolerated due to worsening of motor conditions or occurrence of impulse control disorders.
CONCLUSIONS
This trial provides evidence for simplifying pharmacological treatment after functional neurosurgery for PD. The reduction in dopamine receptor agonists should be attempted while monitoring for occurrence of NMSs, such as apathy and sleep disturbances. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Antiparkinson Agents; Deep Brain Stimulation; Dopamine Agonists; Humans; Levodopa; Parkinson Disease; Single-Blind Method; Treatment Outcome
PubMed: 33165964
DOI: 10.1002/mds.28382 -
Australasian Psychiatry : Bulletin of... Jun 2022Cariprazine is the third partial dopamine agonist now available in Australia. This paper will review the properties, evidence and likely clinical place of cariprazine.
OBJECTIVE
Cariprazine is the third partial dopamine agonist now available in Australia. This paper will review the properties, evidence and likely clinical place of cariprazine.
CONCLUSION
Cariprazine is a partial agonist with high affinity at dopamine D and D receptors, partial agonism at 5HT receptors, moderate 5HT and H antagonism and no anticholinergic activity. It is rapidly absorbed, is unaffected by food, achieves a peak plasma level in 4-8 hours and has high bioavailability. The half-life of cariprazine and its metabolites is long (7-8 days); steady state occurs in 4-8 weeks. It is hepatically metabolized via 3A4 cytochrome enzymes. Cariprazine is an effective antipsychotic in acute schizophrenia in both short and longer placebo-controlled studies. Cariprazine appears to have small advantages in negative symptoms of schizophrenia. While not approved for bipolar disorder, cariprazine is effective in mania and mixed states but requires doses higher than current maximums recommended. Cariprazine causes more akathisia than aripiprazole or brexpiprazole but is less prone to insomnia, weight gain and sedation. Risks for hyperprolactinaemia and QT prolongation are low. Cariprazine is another 'metabolically-friendly' antipsychotic for schizophrenia, with advantages for those with negative symptoms, mood symptoms or problems with adherence.
Topics: Antipsychotic Agents; Dopamine Agonists; Humans; Piperazines; Treatment Outcome
PubMed: 35156402
DOI: 10.1177/10398562211064254 -
Journal of Neurology Nov 2022The development of disease-modifying drugs and differential diagnostic agents is an urgent medical need in Parkinson's disease. Despite the complex pathophysiological... (Review)
Review
The development of disease-modifying drugs and differential diagnostic agents is an urgent medical need in Parkinson's disease. Despite the complex pathophysiological pathway, the misfolding of alpha-synuclein has been identified as a putative biomarker for detecting the onset and progression of the neurodegeneration associated with Parkinson's disease. Identifying the most appropriate alpha-synuclein-based diagnostic modality with clinical translation will revolutionize the diagnosis of Parkinson's. Likewise, molecules that target alpha-synuclein could alter the disease pathway that leads to Parkinson's and may serve as first-in class therapeutics compared to existing treatment options such as levodopa and dopamine agonist that do not necessarily modify the disease pathway. Notwithstanding the promising benefits that alpha-synuclein presents to therapeutics and diagnostics development for Parkinson's disease, finding ways to address potential challenges such as inadequate preclinical models, safety and efficacy will be paramount to achieving clinical translation. In this comprehensive review paper, we described the role of alpha-synuclein in the pathogenesis of Parkinson's disease, as well as how its structure and function relationship delineate disease onset and progression. We further discussed different alpha-synuclein-based diagnostic modalities including biomolecular assays and molecular imaging. Finally, we presented current small molecules and biologics that are being developed as disease-modifying drugs or positron emission tomography imaging probes for Parkinson's disease.
Topics: Biological Products; Biomarkers; Dopamine Agonists; Humans; Levodopa; Parkinson Disease; alpha-Synuclein
PubMed: 35831620
DOI: 10.1007/s00415-022-11267-9 -
The Journal of Neuroscience : the... Feb 2023Impulse control and/or gambling disorders can be triggered by dopamine agonist therapies used to treat Parkinson's disease, but the cognitive and neurobiological...
Impulse control and/or gambling disorders can be triggered by dopamine agonist therapies used to treat Parkinson's disease, but the cognitive and neurobiological mechanisms underlying these adverse effects are unknown. Recent data show that adding win-paired sound and light cues to the rat gambling task (rGT) potentiates risky decision-making and impulsivity via the dopamine system, and that changing dopaminergic tone has a greater influence on behavior while subjects are learning task contingencies. Dopamine agonist therapy may therefore be potentiating risk-taking by amplifying the behavioral impact of gambling-related cues on novel behavior. Here, we show that ropinirole treatment in male rats transiently increased motor impulsivity but robustly and progressively increased choice of the high-risk/high-reward options when administered during acquisition of the cued but not uncued rGT. Early in training, ropinirole increased win-stay behavior after large unlikely wins on the cued rGT, indicative of enhanced model-free learning, which mediated the drug's effect on later risk preference. cFos imaging showed that both chronic ropinirole and the addition of win-paired cues suppressed the activity of dopaminergic midbrain neurons. The ratio of midbrain:prefrontal cFos neurons was lower in animals with suboptimal choice patterns and tended to predict risk preference across all rats. Network analyses further suggested that ropinirole induced decoupling of the dopaminergic cells of the VTA and nucleus accumbens but only when win-paired cues were present. Frontostriatal activity uninformed by the endogenous dopaminergic teaching signal therefore appeared to perpetuate risky choice, and ropinirole exaggerated this disconnect in synergy with reward-paired cues. D receptor agonists, used to treat Parkinson's disease, can cause gambling disorder through an unknown mechanism. Ropinirole increased risky decision-making in rats, but only when wins were paired with casino-inspired sounds and lights. This was mediated by increased win-stay behavior after large unlikely wins early in learning, indicating enhanced model-free learning. cFos imaging showed that ropinirole suppressed activity of midbrain dopamine neurons, an effect that was mimicked by the addition of win-paired cues. The degree of risky choice rats exhibited was uniquely predicted by the ratio of midbrain dopamine:PFC activity. Depriving the PFC of the endogenous dopaminergic teaching signal may therefore drive risky decision-making on-task, and ropinirole acts synergistically with win-paired cues to amplify this.
Topics: Rats; Male; Animals; Dopamine Agonists; Dopamine; Cues; Rats, Long-Evans; Parkinson Disease; Reward; Choice Behavior; Decision Making
PubMed: 36623876
DOI: 10.1523/JNEUROSCI.1459-22.2022 -
Australasian Psychiatry : Bulletin of... Apr 2023We sought to review the effects of Dopamine Receptor Partial Agonist (DRPA) antipsychotic medications on milk supply and breastfeeding. (Review)
Review
OBJECTIVE
We sought to review the effects of Dopamine Receptor Partial Agonist (DRPA) antipsychotic medications on milk supply and breastfeeding.
METHOD
Narrative review of selected literature including animal and human data.
RESULTS
Scant case study evidence suggests that DRPAs may lead to reduced milk supply for some.
CONCLUSIONS
Women taking DRPAs should be advised of the possibility that these may affect milk supply, and reporting should be encouraged to aid future research.
Topics: Animals; Female; Humans; Aripiprazole; Milk; Breast Feeding; Mothers; Dopamine Agonists
PubMed: 36825499
DOI: 10.1177/10398562231159510