Dopamine Agonist Treatment Research Articles

Prevalence of obstructive sleep apnea in patients with prolactinoma before and after treatment with dopamine agonists

Obesity is the main risk factor for the development of obstructive sleep apnea (OSA). Hyperprolactinemia has also been related to obesity. To determine the OSA prevalence in patients with prolactinoma before and after dopamine agonist (DA) and to evaluate the correlation between the apnea-hypopnea index (AHI) and prolactin levels, body mass index (BMI), waist circumference (WC), visceral fat volume (VFV), subcutaneous fat volume, and other metabolic parameters. Thirty-five patients with prolactinoma at baseline and twenty-one who completed the 6-month DA treatment were submitted to clinical/laboratorial evaluations, polysomnography and abdominal imaging. Before treatment, the prevalence of obesity/overweight and OSA were, respectively, 68.5 and 34.2 %. We found a positive correlation between AHI and weight (r = 0.57; p < 0.001), BMI (r = 0.56; p < 0.001), WC (r = 0.61; p < 0.001), VFV (r = 0.55; p = 0.002), insulin levels (r = 0.57; p < 0.001), and HOMA-IR index (r = 0.57; p < 0.001); and a negative correlation between AHI and HDL-cholesterol (r = -0.47; p = 0.005). After multivariate analysis, VFV and insulin levels were the most important predictors for AHI (p = 0.001 and p = 0.02, respectively). After DA, the obesity/overweight and OSA prevalence did not change. The OSA prevalence in patients with prolactinoma is similar to the obese subjects and did not change after treatment. Higher BMI and visceral obesity, but not prolactin levels, seem to be the major factor involved in the occurrence of OSA in these patients.

Unexplained lower limb pain in Parkinson's disease: A phenotypic variant of “painful Parkinson's disease”

Unexplained pain is a key non-motor symptom (NMS) of Parkinson's disease (PD) that is prevalent throughout the condition and often unrecognized and under treated. We have identified a cluster of patients with unexplained refractory and intrusive lower limb pain. MethodsPatients with ‘unexplained’ pain were identified from a survey using a non-motor symptom questionnaire and scale (NMSQuest, NMSS). Patients reporting unexplained severe proximal lower limb pain were then assessed using a newly devised PD pain scale. Co-morbid conditions were excluded and all had lower spine imaging. ResultsFrom a cohort of 225 patients we have identified 22 with unexplained lower limb pain described as persistent leg pain ranging from unilateral to bilateral sometimes associated with whole body pain. None had significant spinal pathology or evidence of large fiber neuropathy. 14 were on regular analgesics with poor effect while 9 took morphine based remedies. Severe unremitting pain led to accidental overdose and death in one patient. All took a combination of levodopa and dopamine agonist treatment including 3 on intrajejunal levodopa infusion. All had high NMSQuest (mean = 17/30) and NMSS (mean = 95 (normal range 30–60)) scores. ConclusionsWe believe that unexplained lower limb pain is a specific non-motor phenotype in Parkinson's disease that is problematic and often undisclosed. This may be a variant of central pain and merits recognition.

Effect of exercise training and dopamine agonists in patients with uremic restless legs syndrome: a six-month randomized, partially double-blind, placebo-controlled comparative study

BackgroundRestless Legs Syndrome is very common in hemodialysis patients however there are no comparative studies assessing the effectiveness of a non-pharmacological treatment to a classical treatment on parameters related to syndromes’ severity and quality of life.MethodsIn this randomized, partially double blind, placebo controlled trial, thirty two hemodialysis patients with restless legs syndrome were randomly assigned into three groups: 1) the exercise training group (N = 16), 2) the dopamine agonists group (ropinirole 0.25 mg/d) (N = 8) and 3) the placebo group (N = 8). The intervention programs lasted 6 months. Restless Legs Syndrome severity was assessed using the international severity scale, physical performance by a battery of tests, muscle size and composition by computed tomography, body composition by Dual Energy X Ray Absorptiometry, while depression score, sleep quality, daily sleepiness and quality of life were assessed through questionnaires.ResultsExercise training and dopamine agonists were effective in reducing syndrome’s symptoms by 46% (P = 0.009) and 54% (P = 0.001) respectively. Within group changes revealed that both approaches significantly improved quality of life (P < 0.05), however, only the dopamine agonists significantly improved sleep quality (P = 0.009). Within group changes showed a tendency for lean body mass improvements with dopamine agonists, this reached statistical significance only with the exercise training (P = 0.014), which also reduced fat infiltration in muscles (P = 0.044) and improved physical performance (P > 0.05) in various tests. Between group changes detect significant improvements with both exercise and dopamine agonists in depression score (P = 0.003), while only the dopamine agonist treatment was able to significantly improve sleep quality, compared to exercise and placebo (P = 0.016).ConclusionsA 6-month exercise training regime was as effective as a 6-month low dosage dopamine agonist treatment in reducing restless legs syndrome symptoms and improving depression score in uremic patients. Further research is needed in order to show whether a combination treatment could be more beneficial for the amelioration of RLS.Trial registrationNCT00942253

Dopamine‐agonists and impulsivity in Parkinson's disease: Impulsive choices vs. impulsive actions

The control of impulse behavior is a multidimensional concept subdivided into separate subcomponents, which are thought to represent different underlying mechanisms due to either disinhibitory processes or poor decision-making. In patients with Parkinson's disease (PD), dopamine-agonist (DA) therapy has been associated with increased impulsive behavior. However, the relationship among these different components in the disease and the role of DA is not well understood. In this imaging study, we investigated in PD patients the effects of DA medication on patterns of brain activation during tasks testing impulsive choices and actions. Following overnight withdrawal of antiparkinsonian medication, PD patients were studied with a H2 ((15)) O PET before and after administration of DA (1 mg of pramipexole), while they were performing the delay discounting task (DDT) and the GoNoGo Task (GNG). We observed that pramipexole augmented impulsivity during DDT, depending on reward magnitude and activated the medial prefrontal cortex and posterior cingulate cortex and deactivated ventral striatum. In contrast, the effect of pramipexole during the GNG task was not significant on behavioral performance and involved different areas (i.e., lateral prefrontal cortex). A voxel-based correlation analysis revealed a significant negative correlation between the discounting value (k) and the activation of medial prefrontal cortex and posterior cingulate suggesting that more impulsive patients had less activation in those cortical areas. Here we report how these different subcomponents of inhibition/impulsivity are differentially sensitive to DA treatment with pramipexole influencing mainly the neural network underlying impulsive choices but not impulsive action.

Impulse Control Disorder in a Patient on Long-Term Treatment With Bromocriptine for a Macroprolactinoma

Impulse control disorders (ICDs) constitute socially disruptive behaviors such as pathological gambling, impulsive eating, compulsive shopping, and hypersexuality. These conditions are well recognized in patients on dopamine agonist (DA) therapy for Parkinson disease. Dopamine agonists are widely used as first-line agents in the treatment of prolactinomas, but ICDs in this group of patients are relatively rare, perhaps because of lower therapeutic doses used. A review of the literature yielded only a few cases of ICDs in patients on DA treatment for prolactinomas. These symptoms are perhaps underreported because of lack of awareness among patients and health care professionals. Impulse control disorders are recognized psychiatric disorders that have significant psychological and social implications, and patients need to be counselled about this rare possibility when embarking on prolonged DA therapy. We describe a young patient with severe, socially disruptive impulsivity manifesting with pathological gambling who had been on long-term bromocriptine therapy for a macroprolactinoma.

Metabolic syndrome associated with hyperprolactinemia: A new indication for dopamine agonist treatment?

In this issue of Endocrine, Inancli and co-authors presentthe manuscript ‘‘Effect of cabergoline on insulin sensitivity,inflammation, and carotid intima media thickness inpatients with prolactinoma’’ [1]. They found that cabergo-line treatment was associated with significant improve-ments in body mass index; total, HDL, and LDL-cholesterollevels and insulin sensitivity, also with a decrease in pro-inflammatory markers and carotid intima media thickness.Only the decrease in total and LDL-cholesterol showed apositive correlation with PRL levels. They concluded thatpatients with prolactinoma may have a higher vascular riskand cabergoline treatment may be associated with betterendothelial function [1].The human prolactin (PRL) is mainly produced bypituitary lactotrophs under inhibitory control of hypotha-lamic dopamine. The main and best-known effect of thePRL is the stimulation of lactogenesis and the maintenanceof lactation (galactopoiesis). However, PRL is also syn-thetized in extra-pituitary sites (decidua, myometrium,lymphocytes, and adipocytes) exerting several functions asa ‘‘metabolic hormone’’ [2–4].The human PRL gene is located on chromosome 6, hassix exons and two transcriptional start sites for extra-pitu-itary and for pituitary PRL. The regulation of PRL genetranscription is also different, requiring interaction withPit-1 at pituitary level and with several not well-knowntissue-specific factors for each extra-pituitary site [4].However, the final protein, PRL, is the same at pituitaryand extra-pituitary sites. In contrast with the pituitary PRLsecretion, the regulation of PRL extra-pituitary secretion islargely unknown.The PRL receptor is widely expressed in human bodyand mediates PRL actions by activation of JAK2/STAT5,PI3K, and MAPK pathways [4]. Regardless of its origin,PRL is able to interact with PRL receptors of any bodylocation. However, the mechanisms regulating the expres-sion of PRL receptor (and its different isoforms) in eachextra-pituitary tissue are basically unknown. This complexsystem could explain the absence of relationship betweencirculating PRL levels and some of the metabolic effects(mainly autocrine or paracrine) of PRL.The metabolic (extra-mammary gland) effects of PRLhave been reviewed elsewhere [2–5] and can be summa-rized as follows: (a) during the perinatal and postnatalperiods pancreatic islet cells development and insulinsecretion are promoted; (b) food intake and weight gainare also promoted; (c) adipogenesis inhibiting lipolysis isstimulated, which alters the release of adipokines includingleptin, adiponectin, and inter-leukin 6, promoting insulinresistance, hyper insulinemia, endothelial dysfunction, andmetabolic syndrome; (d) citrate production in prostaticcells is stimulated and finally, (e) the negative effects ofglucocorticoids on the immune system during stress arecounteracted [6].The appropriate treatment with dopamine agonists inpatients diagnosed with hyperprolactinemia have beenassociated with variable reduction in weight [1, 7], body fat[8], cardiovascular risk markers, cholesterol [1, 9–11], andendothelial dysfunction [1]. In patients with chronic kidney

Evidence-based evaluation of therapeutic measures for sleep disorders

Objective To evaluate the therapeutic efficacy and side effects of various treatment for sleep disorders in order to provide the best therapeutic regimen for the evidence-based treatment of sleep disorders. Methods Sleep disorder, insomnia, restless legs syndrome or RLS, obstructive sleep apnea or OSA, narcolepsy, REM behaviour disorder or RBD, treatment or therapy were used as retrieval words. Cochrane Library, MEDLINE, ScienceDirect were used for retrieval, and manual searching was also used. Related clinical guidelines, systematic reviews, randomized controlled clinical trials, retrospective case analysis, case-observation studies and reviews were collected and evaluated by Jadad Scale. Results Forty related articles were selected as following: 6 clinical guidelines, 12 systematic reviews, 5 randomized controlled trials, 2 retrospective case analysis, 1 case-observation study and 14 reviews. Thirty-three were of high quality, while 7 were of low quality with score. According to the evaluation of therapeutic efficacy and side effects of various therapies, it is suggested as following: 1) insomnia is the most common in sleep disorders; the treatment methods of insomnia mainly include drug therapy and cognitive behavioral treatment (CBT); the two kinds of therapy have their own advantages and disadvantages, and the combination therapy of drugs and CBT is the best treatment plan. 2) The first-line treatment of primary RLS is dopamine agonists and anti-seizure drugs; however, the treatment of secondary RLS is mainly etiologic treatment. 3) The main treatments of OSAS are nasal continuous positive airway pressure (nCPAP), oral orthotics and surgery, and nCPAP is the first-line treatments. 4) The medication of narcolepsy is mainly modafinil, hydroxy butyric acid sodium and antidepressants, and the specific choosing should accord to clinical classifications. 5) The main treatments of RBD include general treatments such as avoiding triggers, insuring the safety of sleep environment, and drug therapy such as benzodiazepines and melatonin. Conclusion Evidence-based medicine can provide the best clinical evidence on sleep disorders' treatment.

Macroprolactinemia in Patients with Prolactinomas: Prevalence and Clinical Significance

Data on the prevalence of macroprolactinemia in patients with prolactinomas is quite limited as the presence of high-molecular prolactin forms is suspected mainly in subjects with mild hyperprolactinemia and negative pituitary imaging. The main objective of this observational case-control study was to assess the prevalence and clinical significance of macroprolactinemia among patients with prolactinomas. The study population consisted of 239 subjects: 131 prolactinoma patients and 108 sex-, age- and ethnicity- matched healthy controls. Macroprolactinemia was defined by a PRL recovery after PEG precipitation of<40%. The prevalence of macroprolactinemia among newly diagnosed prolactinoma patients did not differ statistically from the prevalence in the control group (3.5 vs. 3.7%; p=1.000) but was lower although non-significantly than the subgroup of patients treated with dopamine agonists (DA) (3.5 vs.10.8%; p=0.072). Significant association between disruptions of ovarian function and serum levels of the monomeric as well as high-molecular prolactin isoform was found. In few cases, the presence of typical hyperprolactinemia-related clinical symptoms and their disappearance after treatment with DA suggests biological activity of macroprolactin comparable with that of monomeric prolactin isoform. Decrease of macroprolactin levels after DA treatment could suggest tumoral origin of the high-molecular isoform in these rare cases. Although macroprolactinemia is considered a benign condition, pituitary imaging, DA treatment, and prolonged follow-up may be necessary in certain cases. An individualized approach to the management of patients with macroprolactinemia should be applied.

Reply: Dopamine agonists and delusional jealousy in Parkinson's disease: A cross‐sectional prevalence study

Background: Delusional jealousy (DJ) has been described in patients with Parkinson’s disease (PD) on dopaminergic therapy, but a role for dopaminergic therapy in DJ has not been established. Methods: The current cross-sectional study on DJ investigated its association with dopaminergic therapies compared with their associations with hallucinations and its prevalence in PD patients. Eight hundred five consecutive patients with PD were enrolled between January 2009 and June 2010. Results: DJ was identified in 20 patients (2.48%) and hallucinations in 193 patients (23.98%). In the multivariate logistic regression analyses, dopamine agonists were significantly associated with DJ (odds ratio, 18.1; 95% CI, 3.0–infinity; P 5 .0002) but not with hallucinations (odds ratio, 0.73; 95% CI, 0.49–1.10; P 5 .133). Conclusions: These findings suggest that dopamine agonist treatment represents a risk factor for DJ in PD independent of the presence of a dementing disorder, and the presence of this additional nonmotor side effect should be investigated in this clinical population. V C 2012 Movement Disorder Society Delusional jealousy (DJ), also defined as Othello’s syndrome, is a content-specific delusion characterized by a range of irrational thoughts and emotions, together with associated unacceptable or extreme behavior, in which the dominant theme is a preoccupation with a partner’s sexual unfaithfulness based on unfounded evidence. 1,2 DJ has been described in neurological patients, especially those with right hemispheric stroke 3 and those with neurodegenerative disorders, including Alzheimer’s disease, 4,5 frontotemporal dementia, 5 Lewy body dementia, 5 and Parkinson’s disease (PD). 5‐14

Dopamine agonists modulate the neural network of reward anticipation in Parkinson's disease patients

Dopamine agonists (DA) are widely prescribed to treat Parkinson's disease (PD) but have been found to cause impulse control disorders such as pathological gambling. In a previous study, we found that administration of DA pramipexole in young healthy adults changed the local activity and the connectivity pattern of the nucleus accumbens (NAcc) during reward anticipation. To assess effects of long term DA treatment functional magnetic resonance imaging was used in PD patients in medication-off state (PD-off), the same group of patients in medication-on state (PD-on), and a matched group of healthy controls without medication administration (HC) while they engaged in a reward anticipation task. Compared to HC, PD-off patients showed greater NAcc activity, a stronger interaction between NAcc and the insular cortex, but a weaker interaction between NAcc and the prefrontal cortex. Compared to PD-off, PD-on patients showed less NAcc activity, a weaker insula-striatal connectivity, but a stronger prefrontal-striatal connectivity. The effect of long-term exposure to dopamine agonists thus seems to be different from the effect of short-term medication administration. The change in NAcc activity can be understood in the frame of tonic-phasic dopamine hypothesis. We propose that the imbalance in the connectivity of different reward-related brain areas may underlie the development of pathological gambling in PD patients treated by DA.

Bromocriptine-induced Brainstem Angulation in a Patient With Invasive Prolactinoma

A 29-year-old male patient presented with a 2-year historyof severe frontalheadache,nasalobstruction,and visual defects in April 2004, along with increased prolactin level (16 808 ng/ml) and decreased cortisol level (8.3 g/L). Brain magnetic resonance imaging (MRI) (Figure 1, A–C) showed that a giant invasive prolactinoma and odontoid processexceededchamberlain lineover1.3cmandthebrainstem at an angle of 36.5° (Figure 1B). A computed tomography scan (Figure 2, A–D) showed that the clivus and occipitalwereseriouslydestroyed.Thepatientwas treatedwith bromocriptine (BRC), which was gradually increased to 15 mg/d, and no side effect was observed. The serum prolactin level also returned to normal in November 2006. Ten months after BRC treatment, MRI (Figure 1, D–F) revealed that the size of the prolactinoma was significantly reduced and that the bone of total clivus had disappeared and the brainstem crawled over the bulgy odontoid process (the angle of brainstem was 61.1°; Figure 1E). Similar magnetic resonance images were found in January 2012 (Figure 1, G–I). Some complications associated with dopamine agonist treatment for prolactinomas, such as cerebrospinal rhinorrhea(1),emptysella turcica (2),andopticchiasmaherniation (3), have been reported. To the best of our knowledge, we first report here that a male patient with invasive prolactinoma developed the brainstem angulation, which crawls over the bulgy odontoid process, after BRC treatment. Studies show that occipito-cervical fusion is necessary for the cranio-cervical joint instability due to skull base bone destruction (4,5).However, theworseangulationofbrainstem and symptoms were not observed after BRC and cortisol replacement therapy in the follow-up period without the occipito-cervical fusion.

Untethering of herniated left optic nerve after dopamine agonist treatment for giant prolactinoma

Untethering of herniated left optic nerve after dopamine agonist treatment for giant prolactinoma

Macroprolactinemia in a Patient with Invasive Macroprolactinoma: A Case Report and Minireview

Background. Macroprolactin, the high-molecular prolactin isoform, is considered to be an inactive in vivo product with extrapituitary origin. Patients with macroprolactinemia are usually asymptomatic, with negative pituitary imaging. Based on these data, most authors do not recommend treatment and long-term followup in subjects with macroprolactinemia. However, there is evidence for overlapping clinical features among subjects with hyperprolactinemia due to monomeric or “big big” PRL isoform. Case Presentation. We present a 35-year-old female patient with secondary amenorrhea, mild obesity, hirsutism, headache and blurred vision. Hormonal evaluation revealed an extreme hyperprolactinemia (PRL = 10 610 mIU/L) almost exclusively due to macroprolactin isoform (MPRL = 10 107 mIU/L; recovery after PEG precipitation 4.7%) and hypogonadotropic hypogonadism. An invasive pituitary macroadenoma was visualized on MRI, and cabergoline therapy was initiated. Disappearance of clinical signs and symptoms, normalization of gonadotropin levels, and restoration of regular ovulatory menstrual cycles after 1 year of treatment are arguments in favor of preserved-macroprolactin bioactivity in this case. The significant decrease in MPRL levels and tumor volume in response to dopamine agonist therapy is suggestive for the tumoral origin of this isoform. Conclusions. Although macroprolactinemia is considered to be a benign condition, pituitary imaging, dopamine agonist treatment, and prolonged followup should be recommended in some particular cases.

1H MRSI of middle frontal gyrus in pediatric ADHD

Neuroimaging studies in multiple modalities have implicated the left or right dorsolateral prefrontal cortex (here, middle frontal gyrus) in attentional functions, in ADHD, and in dopamine agonist treatment of ADHD. The far lateral location of this cortex in the brain, however, has made it difficult to study with magnetic resonance spectroscopy (MRS). We used the smaller voxel sizes of the magnetic resonance spectroscopic imaging (MRSI) variant of MRS, acquired at a steep coronal-oblique angle to sample bilateral middle frontal gyrus in 13 children and adolescents with ADHD and 13 age- and sex-matched healthy controls. Within a subsample of the ADHD patients, aspects of attention were also assessed with the Trail Making Task. In right middle frontal gyrus only, mean levels of N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (tNAA), creatine + phosphocreatine (Cr), choline-compounds (Cho), and myo-inositol (mI) were significantly lower in the ADHD than in the control sample. In the ADHD patients, lower right middle frontal Cr was associated with worse performance on Trails A and B (focused attention, concentration, set-shifting), while the opposite relationship held true for the control group on Trails B. These findings add to evidence implicating right middle frontal cortex in ADHD. Lower levels of these multiple species may reflect osmotic adjustment to elevated prefrontal cortical perfusion in ADHD and/or a previously hypothesized defect in astrocytic production of lactate in ADHD resulting in decelerated energetic metabolism (Cr), membrane synthesis (Cho, mI), and acetyl-CoA substrate for NAA synthesis. Lower Cr levels may indicate attentional or executive impairments.

Rebalance of Striatal NMDA/AMPA Receptor Ratio Underlies the Reduced Emergence of Dyskinesia During D2-Like Dopamine Agonist Treatment in Experimental Parkinson's Disease

Dopamine replacement with levodopa (L-DOPA) represents the mainstay of Parkinson’s disease (PD) therapy. Nevertheless, this well established therapeutic intervention loses efficacy with the progression of the disease and patients develop invalidating side effects, known in their complex as L-DOPA-induced dyskinesia (LID). Unfortunately, existing therapies fail to prevent LID and very few drugs are available to lessen its severity, thus representing a major clinical problem inPDtreatment. D2-like receptor (D2R) agonists are a powerful clinical option as an alternative to L-DOPA, especially in the early stages of the disease, being associated to a reduced risk of dyskinesia development. D2R agonists also find considerable application in the advanced stages of PD, in conjunction with L-DOPA, which is used in this context at lower dosages, to delay the appearance and the extent of the motor complications. In advanced stages of PD, D2R agonists are often effective in delaying the appearance and the extent of motor complications. Despite the great attention paid to the family of D2R agonists, the main reasons underlying the reduced risk of dyskinesia have not yet been fully characterized. Here we show that the striatal NMDA/AMPAreceptor ratio and theAMPAreceptor subunit composition are altered in experimental parkinsonism in rats. Surprisingly, while L-DOPA fails to restore these critical synaptic alterations, chronic treatment with pramipexole is associated not only with a reduced risk of dyskinesia development but is also able to rebalance, in a dose-dependent fashion, the physiological synaptic parameters, thus providing new insights into the mechanisms of dyskinesia.

Pramipexole-Induced Obsessive-Compulsive Symptoms in a Patient with Parkinson's Disease and Disgust Sensitivity

While literature supports the phenomenological links between Parkinson’s disease (PD), obsessive-compulsive disorder (OCD), and impulse control disorders, the neurobiological underpinnings have yet to be established. Parkinson’s disease and its treatment have been implicated in the development of impulsive behaviors, including hypersexuality and pathologic gambling. They have not, however, been reported to induce frank OCD. In this case, we present a patient with PD and heightened disgust sensitivity who developed pramipexole-induced contamination OCD. As disgust sensitivity is positively correlated with the contamination subtype of OCD, this case illustrates the value of screening for this trait when patients require dopamine agonist treatment.

Prefrontal cortex, dopamine, and jealousy endophenotype

Jealousy is a complex emotion characterized by the perception of a threat of loss of something that the person values,particularly in reference to a relationship with a loved one, which includes affective, cognitive, and behavioral components. Neural systems and cognitive processes underlying jealousy are relatively unclear, and only a few neuroimaging studies have investigated them. The current article discusses recent empirical findings on delusional jealousy, which is the most severe form of this feeling, in neurodegenerative diseases. After reviewing empirical findings on neurological and psychiatric disorders with delusional jealousy, and after considering its high prevalence in patients with Parkinson's disease under dopamine agonist treatment, we propose a core neural network and core cognitive processes at the basis of (delusional) jealousy, characterizing this symptom as possible endophenotype. In any case,empirical investigation of the neural bases of jealousy is just beginning, and further studies are strongly needed to elucidate the biological roots of this complex emotion.

Dopamine agonists and delusional jealousy in Parkinson's disease: A cross‐sectional prevalence study

Delusional jealousy (DJ) has been described in patients with Parkinson's disease (PD) on dopaminergic therapy, but a role for dopaminergic therapy in DJ has not been established. The current cross-sectional study on DJ investigated its association with dopaminergic therapies compared with their associations with hallucinations and its prevalence in PD patients. Eight hundred five consecutive patients with PD were enrolled between January 2009 and June 2010. DJ was identified in 20 patients (2.48%) and hallucinations in 193 patients (23.98%). In the multivariate logistic regression analyses, dopamine agonists were significantly associated with DJ (odds ratio, 18.1; 95% CI, 3.0-infinity; P = .0002) but not with hallucinations (odds ratio, 0.73; 95% CI, 0.49-1.10; P = .133). These findings suggest that dopamine agonist treatment represents a risk factor for DJ in PD independent of the presence of a dementing disorder, and the presence of this additional nonmotor side effect should be investigated in this clinical population.

Risk Factors Identified for Impulse Control Disorders in Parkinson's

Risk Factors Identified for Impulse Control Disorders in Parkinson's

Long‐term efficacy and safety of safinamide as add‐on therapy in early Parkinson's disease

Safinamide is an α-aminoamide with both dopaminergic and non-dopaminergic mechanisms of action in Phase III clinical development as a once-daily add-on to dopamine agonist (DA) therapy for early Parkinson's disease (PD). Study 017 was a 12-month, randomized, double-blind, placebo-controlled pre-planned extension study to the previously reported Study 015. Patients received safinamide 100 or 200 mg/day or placebo added to a single DA in early PD. The primary efficacy endpoint was the time from baseline (Study 015 randomization) to 'intervention', defined as increase in DA dose; addition of another DA, levodopa or other PD treatment; or discontinuation due to lack of efficacy. Safinamide groups were pooled for the primary efficacy endpoint analysis; post hoc analyses were performed on each separate dose group. Of the 269 patients randomized in Study 015, 227 (84%) enrolled in Study 017 and 187/227 (82%) patients completed the extension study. Median time to intervention was 559 and 466 days in the pooled safinamide and placebo groups, respectively (log-rank test; P = 0.3342). In post hoc analyses, patients receiving safinamide 100 mg/day experienced a significantly lower rate of intervention compared with placebo (25% vs. 51%, respectively) and a delay in median time to intervention of 9 days (P < 0.05; 240- to 540-day analysis). The pooled data from the safinamide groups failed to reach statistical significance for the primary endpoint of median time from baseline to additional drug intervention. Post hoc analyses indicate that safinamide 100 mg/day may be effective as add-on treatment to DA in PD.