Side Effects Of Dopamine Agonists Research Articles

Current and Perspective Approaches to the Treatment of Prolactinomas.

Along with the presence of the 2011 Endocrine Society Clinical Practice Guidelines and numerous large-scale studies on the treatment of hyperprolactinemia of different origin, there are some unresolved questions, ambiguous and sometimes contradictory points of view regarding the management of patients with prolactinomas. This overview is devoted to the analysis of the results of modern clinical studies and the approaches towards the management of hyperprolactinemia caused by prolactinoma. A systematic research of the literature for the appropriate keywords published mainly for the last 10 years was done; also, a reference list of each selected article was analysed. We included to our review the articles reporting controversial issues or new data on the treatment of hyperprolactinemia. The review describes various problems arising during the treatment of prolactinoma. The presence of primary and secondary dopamine agonist resistance in each case requires an individual approach, and sometimes may include the use of the antineoplastic agent t emozolomide. The side effects of dopamine agonists are discussed, with quite rare ones, including valvulopathy, pathological psychological conditions and cerebrospinal rhinorrhea. The controversial issue of the duration and doses of the drug used to achieve a lasting effect in the treatment of prolactinomas is considered. There are some points connected with the frequency of relapses. Thus, recurrence is correlated to the duration of treatment with dopamine agonists, prolactin levels at diagnosis, and the initial tumor size. Metformin, somatostatin analogues, selective estrogen receptor modulators, tyrosine kinase inhibitors, inhibitors of the mammalian target of rapamycin, epidermal growth factor receptor antagonists are investigated nowadays as potential alternative methods of drug treatment of prolactinomas. Drug therapy with dopamine agonists makes it possible to achieve the desired results in the vast majority of patients. However, despite the proven safety of this group of medicines, the risk of side effects should still be taken into account. The therapy regimen should be determined by the clinical course of prolactinoma and the patient's response to treatment. Other options of treatment should be considered in patients intolerant to medical therapy, with contraindication or resistance to dopamine agonists, in the case of a malignant tumor. The presence of refractory to any of the applied methods of treatment and aggressive prolactinomas leads to the search for new drugs.

Change in Insulin Sensitivity and Lipid Profile After Dopamine Agonist Therapy in Patients With Prolactinoma.

BackgroundProlactinomas are prolactin(PRL)-secreting neoplastic lesions that can lead to metabolic disturbances and insulin resistance. We aimed to find the change in insulin sensitivity and lipid profile in prolactinoma patients after dopamine therapy. MethodologyA prospective observational study was conducted at the Hayatabad Medical Complex, Peshawar between June 2019 to July 2020. All patients with newly diagnosed prolactinoma were eligible to partake in the study. Individuals with multiple hormone-producing pituitary tumors, hyperprolactinemia secondary to other causes than tumors, and those taking medication for hypercholesterolemia were excluded. Diagnosis of prolactinoma was established on the basis of elevated PRL levels on at least two occasions three days apart in addition to an MRI detecting prolactinoma on the hypothalamic-pituitary area. The mean dose for dopamine agonist was 5.8 ± 4.1 mg per day with a range between 1.25 to 15 mg. To assess the change in insulin resistance, the homeostatic model assessment insulin resistance (HOMA-IR) was computed. All data were recorded in a predefined proforma. Results The difference between pre- and post-treatment values for mean PRL levels was statistically significant (p<0.0001). There was a significant association between dopamine agonist treatment and the BMI (pre- vs. post-treatment; 28.9 ± 4.28 vs. 24.53 ± 2.2, p<0.0001). Both low-density lipoprotein (LDL)-cholesterol and HOMA-IR scores were significantly lower in the post-treatment group as compared to the pre-treatment group (p<0.0001). ConclusionThe present study indicated that dopamine agonist therapy was effective not only in lowering the serum PRL levels but also improved insulin sensitivity and decreased lipid metabolism, resulting in improved BMI. Further studies should explore the long-term side effects of dopamine agonists on patients with prolactinoma.

Increased prevalence of impulse control disorder symptoms in endocrine diseases treated with dopamine agonists: a cross-sectional study

IntroductionImpulse control disorders (ICDs) have been described as a side effect of dopamine agonists (DAs) in neurological as well as endocrine conditions. Few studies have evaluated the neuropsychological effect of DAs in hyperprolactinemic patients, and these have reported a relationship between DAs and ICDs. Our objective was to screen for ICD symptoms in individuals with DA-treated endocrine conditions.Materials and methodsA cross-sectional analysis was conducted on 132 patients with pituitary disorders treated with DAs (DA exposed), as well as 58 patients with pituitary disorders and no history of DA exposure (non-DA exposed). Participants responded to the full version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s disease (QUIP).ResultsCompared with the non-DA-exposed group, a higher prevalence of DA-exposed patients tested positive for symptoms of any ICD or related behavior (52% vs. 31%, p < 0.01), any ICD (46% vs. 24%, p < 0.01), any related behavior (31% vs. 17%, p < 0.05), compulsive sexual behavior (27% vs. 14%, p < 0.04), and punding (20% vs. 7%, p < 0.02) by QUIP. On univariate analysis, DA treatment was associated with a two- to threefold increased risk of any ICD or related behavior [odds ratio (OR) 2.43] and any ICD (OR 2.70). In a multivariate analysis, independent risk factors for any ICD or related behavior were DA use (adjusted OR 2.22) and age (adjusted OR 6.76). Male gender was predictive of the risk of hypersexuality (adjusted OR 3.82).DiscussionDespite the QUIP limitations, a clear sign of increased risk of ICDs emerges in individuals with DA-treated pituitary disorders. Our data contribute to the growing evidence of DA-induced ICDs in endocrine conditions.

Changes in Prescribing Practices of Dopaminergic Medications in Individuals with Parkinson's Disease by Expert Care Centers from 2010 to 2017: The Parkinson's Foundation Quality Improvement Initiative

During the past decade, there has been increasing awareness of the side effects of dopamine agonists (DAs), including impulse control disorders. We hypothesized that there may be a shift toward more conservative use of DAs. To explore the change in prescribing practices for dopaminergic medications in Parkinson's disease between 2010 and 2017. Data were collected from the Parkinson's Foundation Quality Improvement Initiative registry. Baseline characteristics were compared between the 2010 and 2017 cohorts using chi-squared tests for discrete and t tests for continuous variables. Logistic regressions were conducted for each class of medications to assess the effect of time points (2010 vs. 2017) and prespecified covariates on the probability of prescribing. A total of 2,717 participants from 2010 and 2,900 participants from 2017 were included in the analysis. Mean (standard deviation) age was 67.4 (10) and 68.7 (9.3) for the 2010 and 2017 cohorts, respectively (P < 0.0001). After controlling for baseline characteristics, DA use was unchanged (P = 0.1172). The odds of using monoamine oxidase B inhibitors was 52% higher in 2017 than in 2010 (P < 0.0001), 38% lower for catechol-O-methyltransferase inhibitors (P < 0.0001), 25% lower for amantadine (P < 0.0001), and 31% lower for anticholinergics (P = 0.0153). There was no difference in the utilization of levodopa in the 2 cohorts (86.1% vs. 86.2%; P = 0.5783). Despite increasing awareness of impulse control disorders, there has been no reduction in the use of DAs during the past decade. Overall, there is less utilization of adjunctive classes of drugs except for an increase in the use of monoamine oxidase B inhibitors.

Editorial introductions

Current Opinion in Neurology was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of neurology is divided into 14 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Stefan KlöppelStefan KlöppelProf. Stefan Klöppel studied medicine at the University Medical Centers in Freiburg, Germany, and Vienna, Austria. He specialised in Psychiatry and Psychotherapy at the University Medical Centers in Hamburg, London and Freiburg. He was head of the Memory Clinic in Freiburg and of Freiburg Brain Imaging. In December 2016, he became Chairman of the University Hospital of Old Age Psychiatry at the University of Bern (Switzerland). His research aims to improve imaging based diagnostics in dementia and to develop individualised non-pharmacological treatments of cognitive impairment. Per SvenningssonPer SvenningssonPer Svenningsson is Professor in Neurology at the Karolinska Institutet, Sweden. He received his MD and PhD from Karolinska Institutet in 1998. He then did his postdoctoral training in the laboratory of the Nobel laureate Paul Greengard at the Rockfeller University, USA, between 1999 and 2003. His studies concerned GPCR neuropharmacology and signal transduction and included the discovery of p11 as an important modulator of serotonin neurotransmission. He performed his residency in Neurology at Karolinska University Hospital and became Professor in 2012 and senior physician in 2016. His research interests include GPCR pharmacology, Parkinson's disease both its motor and non-motor aspects and atypical parkinsonism. Studies are conducted both in preclinical models and in specimens from patients. The goal is to identify novel targets for improved diagnostics and pharmacological receptor-based treatments. Biochemical, histological, pharmacological, molecular biological and behavioral techniques are used. At the clinical side, he is conducting clinical trials with therapies aiming to slow down progression of Parkinson's disease or to treat debilitating symptoms of the disease. He has published more than 200 articles. Since 2014, he is member of the Nobel Assembly annually awarding the Nobel Prize in Physiology or Medicine. Steven J. FruchtSteven J. FruchtDr Frucht is currently Professor of Neurology and Director of Movement Disorders at NYU Langone Medical Center in New York City, USA. He has devoted his career to the care and management of patients with movements disorders, particularly those with rare or treatment refractory hyperkinetic movement disorders. He has published over 180 PubMed referenced papers, written two books, and lectured more than forty times at the International Movement Disorders Congress and American Academy of Neurology annual meetings. Among his research accomplishment, he was the first to describe sleep attacks as a side effect of dopamine agonists in Parkinson's disease, to define the metabolic topography of posthypoxic myoclonus, and to demonstrate the efficacy of sodium oxybate in a variety of alcohol responsive hyperkinetic movement disorders. He has published extensively on the phenomenology of dystonia, including musicians’ dystonia and other unusual focal task-specific dystonia. He has helped to train more than thirty fellows, many of whom have pursued careers in academic movement disorders. Doris A. TraunerDoris A. TraunerDr Doris A. Trauner is a Distinguished Professor of Neurosciences at the University of California San Diego School of Medicine, USA. After earning her medical degree at the Medical College of Virginia, Dr Trauner completed an internship and a residency at UC San Diego, followed by a fellowship at the University of Chicago, USA. She is board certified in pediatrics, child neurology and neurodevelopmental disorders. She has held a joint appointment in the UC San Diego Neurosciences and Pediatrics Departments since 1977 and served as the chief of pediatric neurology from 1981 to 2015. She has served on numerous national and local committees, including as chair of several national and UCSD committees. She has received numerous awards, most recently the Lifetime Achievement Award from the Child Neurology Society. Dr Trauner's research focuses on the cognitive consequences of conditions that alter brain development early in life, including both structural and metabolic disorders. She studies children with neurodevelopmental, genetic and metabolic disorders. She has over 200 publications including research articles and book chapters, as well as two books. Dr Trauner also teaches undergraduate and graduate students, medical students and residents. In addition, she maintains an active clinical practice in pediatric neurology, with clinical interests encompassing the entire spectrum of neurodevelopmental disorders, including autism spectrum disorders, language impairment, developmental delay, neurobehavioral disorders and epileptic behavior syndromes.

Treating the Motor Symptoms of Parkinson Disease.

After a patient is diagnosed with Parkinson disease (PD), there are many therapeutic options available. This article provides examples of prototypical patients encountered in clinical practice and illustrates the various pharmacologic and nonpharmacologic treatment options for the motor symptoms of PD. Levodopa became available in the late 1960s and remains the gold standard for the treatment of PD even today. Since that time, amantadine, monoamine oxidase type B inhibitors, dopamine agonists, and catechol-O-methyltransferase inhibitors have emerged as monotherapy, add-on therapies, or both, in the armamentarium against PD. The most appropriate time to start such drugs remains a clinical decision according to patient symptoms. However, earlier use of levodopa is the more common practice due to its superior benefit and the side effects of dopamine agonists. Deep brain stimulation continues to be the most effective treatment for motor symptoms in appropriate patients, and advances in technology may improve efficacy. New ways to deliver levodopa have emerged (effective extended-release oral preparations and levodopa/carbidopa intestinal gel), and these medications provide additional options for certain patients. Exercise and neurorehabilitation are increasingly recognized as important tools to combat the motor symptoms of PD. Nondopaminergic drugs may help non-levodopa-responsive motor symptoms. Treatment of PD is multifaceted and requires a tailored pharmacotherapeutic and nonpharmacologic approach for a given patient. Patients should be at the center of care, and clinicians should try to provide optimum benefit through the many treatment options available.

Self-Limited Kleptomania Symptoms as a Side Effect of Duloxetine.

Introduction. Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists, frequently used in neurodegenerative conditions affecting the nigrostriatal pathway. Serotonin-norepinephrine reuptake inhibitors (e.g., duloxetine) have dose-dependent differential affinity for monoaminergic transporters, inhibiting the dopamine transporter at higher doses, thus increasing availability of synaptic dopamine, with the potential for similar impulse control side effects. Case Presentation. A 19-year-old Asian-American female with a history of depression developed new-onset stealing behaviors after an increase in her dose of duloxetine from 60 mg to 90 mg; she described these actions as “compulsive” and irresistible, later experiencing either relief or guilt, features compatible with an ICD. Her symptoms eventually subsided with continued use of 90 mg of duloxetine. Discussion. To the knowledge of the authors, this is the first report of a patient developing new-onset ICD behaviors after being placed on a higher dose of duloxetine, which can inhibit the dopamine transporter and cause difficulty with impulse control. The self-resolving nature of the symptoms may result from compensatory upregulation of dopamine transporters, increasing reuptake of dopamine. Asian populations may be at a higher risk due to the frequent occurrence of CYP2D6 polymorphisms, which decrease the conversion of duloxetine to its inactive metabolites.

Current Indications for the Surgical Treatment of Prolactinomas

Introduction: Prolactin-secreting lesions represent the most common subtype of all pituitary tumors, approximately 40% of diagnosed pituitary adenomas. Prolactinomas are unique in that they are the only type of pituitary adenoma that can be treated quite effectively with medications in the form of dopamine agonists (DAs). Transsphenoidal surgery (TSS) may be indicated in prolactinoma patients who are resistant to DA therapy, intolerant of their side effects, or both. Approximately 10% of patients will fail medical therapy and have no tumor shrinkage, refractory serum prolactin levels, and/or intolerable side effects of DAs, and subsequently become candidates for surgical resection. We examine the current indications for TSS in the prolactinoma patient population.

A Possible Case of Peduncular Hallucinosis in a Patient with Parkinson's Disease Successfully Treated With Quetiapine

Back to table of contents Previous article Next article LETTERFull AccessA Possible Case of Peduncular Hallucinosis in a Patient with Parkinson’s Disease Successfully Treated With QuetiapineDavid R. Spiegel M.D.Brandy Lybeck B.S.Victoria Angeles M.D.,David R. Spiegel M.D.Search for more papers by this authorBrandy Lybeck B.S.Search for more papers by this authorVictoria Angeles M.D.Search for more papers by this author,Published Online:1 Apr 2009https://doi.org/10.1176/jnp.2009.21.2.225aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Peduncular hallucinosis was first described by Lhermitt as odd visual hallucinations stemming from lesions affecting the midbrain, pons, and thalamus. 1 We report on an elderly female with Parkinson’s disease who possibly exhibits this rare form of perceptual disturbance. Case Report Our patient is a 76-year-old Caucasian woman with a 3-year history of Parkinson’s disease, presenting with acute dyspnea which resulted in her hospitalization. She reported visual hallucinations of “mechanical bugs walking around the hospital” and “two people fighting” in the corner of her room. The visual hallucinations began 1 year prior to her hospitalization and were nondistressing. She had insight into the visual hallucinations. Our patient was treated with carbidopa- l -dopa until 4 months prior to admission. The patient’s mental status exam was notable for bradyphasia, psychomotor retardation, and limited range of affect. She had signs of a pill rolling tremor on her left hand. She was otherwise alert and oriented times 3 with no fluctuations in consciousness. She reports visual hallucinations in the absence of bizarre delusions or auditory hallucinations. Cognitive examination was notable for deficits in short-term recall (which improved with cues) and attention span. An MRI scan of the brain revealed a hyper-intense focus adjacent to the right thalamus consistent with an old lacunar infarct. An EEG revealed no eliptiform discharges or significant slowing.Our patient was treated with quetiapine for the visual hallucinations, with a noted decrease in the number of hallucinations for the remainder of the hospital stay.Discussion Visual hallucinations often suggest a wide range of etiologies. Hallucinations and delusions occur in up to 40% of patients with Parkinson’s disease. Visual hallucinations are typically associated as a side effect of dopamine agonists, such as carbidopa- l -dopa, in about 20% of Parkinson’s disease patients; however, our patient’s visual hallucinations persisted despite discontinuation of carbidopa- l -dopa. 2 The differential diagnosis for visual hallucinations includes neurodegenerative dementias, such as Parkinson’s dementia, postictal states, intoxications/delirium tremens, migraine headache with aura, and narcolepsy. 3 Peduncular hallucinosis is a rare form of visual hallucination characterized by intense, vividly colored, nonstereotypical visual images of people, animals, and plants that are nonthreatening to the patient. The exact mechanism for peduncular hallucinosis is unknown. One theory is that when “normal” afferent input is decreased, for example by diminished visual acuity, spontaneous cerebral activity of the visual system is disinhibited, resulting in visual hallucinations. However, given the rarity of such cases, it may be that cerebral pathology may render some elderly patients vulnerable to this disinhibited phenomena associated with pontine lesions. 4 However, according to Cubo et al., 5 visual hallucinations are more likely to occur with more severe overall Parkinson’s symptoms and longer duration of Parkinson’s disease. Our patient only had Parkinson’s disease for 3 years and was only mildly impaired by the illness. Thus, based on clinical and radiographic findings, peduncular hallucinosis was considered in the differential diagnosis of our patient’s visual hallucinations. In closing, the emergence of new-onset visual hallucinations in the elderly warrants an MRI of the brain and, although rare, peduncular hallucinosis should be considered in the differential diagnosis, especially with brain stem or thalamic infarcts. Department of Psychiatry, Eastern Virginia Medical School, Norfolk, Virginia

A Possible Case of Peduncular Hallucinosis in a Patient with Parkinson’s Disease Successfully Treated With Quetiapine

Back to table of contents Previous article Next article LETTERFull AccessA Possible Case of Peduncular Hallucinosis in a Patient with Parkinson’s Disease Successfully Treated With QuetiapineDavid R. Spiegel M.D.Brandy Lybeck B.S.Victoria Angeles M.D.,David R. Spiegel M.D.Search for more papers by this authorBrandy Lybeck B.S.Search for more papers by this authorVictoria Angeles M.D.Search for more papers by this author,Published Online:1 Apr 2009https://doi.org/10.1176/jnp.2009.21.2.225aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Peduncular hallucinosis was first described by Lhermitt as odd visual hallucinations stemming from lesions affecting the midbrain, pons, and thalamus. 1 We report on an elderly female with Parkinson’s disease who possibly exhibits this rare form of perceptual disturbance. Case Report Our patient is a 76-year-old Caucasian woman with a 3-year history of Parkinson’s disease, presenting with acute dyspnea which resulted in her hospitalization. She reported visual hallucinations of “mechanical bugs walking around the hospital” and “two people fighting” in the corner of her room. The visual hallucinations began 1 year prior to her hospitalization and were nondistressing. She had insight into the visual hallucinations. Our patient was treated with carbidopa- l -dopa until 4 months prior to admission. The patient’s mental status exam was notable for bradyphasia, psychomotor retardation, and limited range of affect. She had signs of a pill rolling tremor on her left hand. She was otherwise alert and oriented times 3 with no fluctuations in consciousness. She reports visual hallucinations in the absence of bizarre delusions or auditory hallucinations. Cognitive examination was notable for deficits in short-term recall (which improved with cues) and attention span. An MRI scan of the brain revealed a hyper-intense focus adjacent to the right thalamus consistent with an old lacunar infarct. An EEG revealed no eliptiform discharges or significant slowing.Our patient was treated with quetiapine for the visual hallucinations, with a noted decrease in the number of hallucinations for the remainder of the hospital stay.Discussion Visual hallucinations often suggest a wide range of etiologies. Hallucinations and delusions occur in up to 40% of patients with Parkinson’s disease. Visual hallucinations are typically associated as a side effect of dopamine agonists, such as carbidopa- l -dopa, in about 20% of Parkinson’s disease patients; however, our patient’s visual hallucinations persisted despite discontinuation of carbidopa- l -dopa. 2 The differential diagnosis for visual hallucinations includes neurodegenerative dementias, such as Parkinson’s dementia, postictal states, intoxications/delirium tremens, migraine headache with aura, and narcolepsy. 3 Peduncular hallucinosis is a rare form of visual hallucination characterized by intense, vividly colored, nonstereotypical visual images of people, animals, and plants that are nonthreatening to the patient. The exact mechanism for peduncular hallucinosis is unknown. One theory is that when “normal” afferent input is decreased, for example by diminished visual acuity, spontaneous cerebral activity of the visual system is disinhibited, resulting in visual hallucinations. However, given the rarity of such cases, it may be that cerebral pathology may render some elderly patients vulnerable to this disinhibited phenomena associated with pontine lesions. 4 However, according to Cubo et al., 5 visual hallucinations are more likely to occur with more severe overall Parkinson’s symptoms and longer duration of Parkinson’s disease. Our patient only had Parkinson’s disease for 3 years and was only mildly impaired by the illness. Thus, based on clinical and radiographic findings, peduncular hallucinosis was considered in the differential diagnosis of our patient’s visual hallucinations. In closing, the emergence of new-onset visual hallucinations in the elderly warrants an MRI of the brain and, although rare, peduncular hallucinosis should be considered in the differential diagnosis, especially with brain stem or thalamic infarcts. Department of Psychiatry, Eastern Virginia Medical School, Norfolk, Virginia

Efficacy of cabergoline in restless legs syndrome

To assess the efficacy and safety of the dopamine agonist cabergoline in the treatment of patients with idiopathic restless legs syndrome (CATOR study). Patients with moderate to severe restless legs syndrome (RLS) were randomly assigned to cabergoline (single evening dose: 2 mg) or placebo and treated for 5 weeks in a double-blind, multicenter polysomnography (PSG) trial. The primary efficacy measures were the periodic leg movements during sleep arousal index (PLMS-AI) and sleep efficiency. These and further PSG variables were monitored by centrally evaluated PSG. Severity of RLS was assessed using the International RLS Study Group Severity Scale (IRLS), the RLS-6 scales, the Sleep Questionnaire Form A (SF-A; quality of sleep), and the Quality of Life for RLS questionnaire. Forty-three patients were treated and 40 patients were evaluated with PSG (age 56 +/- 10 years, 73% women). Cabergoline was superior to placebo in terms of the PLMS-AI (-17.7 +/- 16.4 vs -4.5 +/- 20.0 placebo; p = 0.0024), sleep efficiency (+6.2 +/- 13.9% vs +3.3 +/- 11.7%; p = 0.0443), PLMS index (p = 0.0014), PLM index (p = 0.0012), and total sleep time (p = 0.0443). Improvements in IRLS total score (-23.7 +/- 11.2 vs -7.9 +/- 11.0 placebo; p = 0.0002), RLS-6 severity scales during the night (p = 0.0010) and during the day (p = 0.0018), Clinical Global Impressions severity item (p = 0.0003), sleep quality (p = 0.0180), SF-A sleep quality (p = 0.0371), and QoL-RLS (p = 0.0247) were larger in patients treated with cabergoline compared with the placebo group. Adverse events were only mild and well-known side effects of dopamine agonists. Single-evening cabergoline is an efficacious and well-tolerated short-term therapy for sensorimotor symptoms of restless legs syndrome and associated sleep disturbances.