María Verónica Rey

Prevalence and pharmacological factors associated with impulse-control disorder symptoms in patients with Parkinson disease.

BackgroundImpulse-control disorders (ICDs) occur in patients with Parkinson disease (PD), especially in younger patients on dopamine therapies. ObjectiveTo assess the prevalence of ICD symptoms and its pharmacological correlations in a sample of French patients with PD and without PD (poststroke). MethodsOutpatients with PD and without PD (poststroke) were screened for compulsive behaviors related to hypersexuality, compulsive shopping, pathological gambling, or compulsive eating by means of the Questionnaire for Impulse-Control Disorders—short version. Full medical history and Unified Parkinson’s Disease Rating Scale scores were also recorded. Dose of dopamine agonists were converted to defined daily doses (DDDs), according to the World Health Organization Anatomical Therapeutic Chemical classification system classification system. ResultsTwo hundred three patients with PD and 52 patients without PD were recruited (mean ± SD age, 67 ± 1 vs 69 ± 2, P= 0.4; males: 62% vs 55% P= 0.2). Symptoms of ICDs were reported by 0% of poststroke patients and 25% of the patients with PD (P < 0.001). Hypersexuality was reported by 10% of the patients with PD, compulsive shopping by 6%, pathological gambling by 3%, and compulsive eating by 14%. A logistic regression analysis found that age younger than 68 years (odds ratio [OR], 3.3; 95% confidence interval, 1.6–6.6) and exposure to dopamine agonists (OR, 20.3; 95% confidence interval, 2.7–65.0) or monoaminooxidase-B inhibitor (OR, 3.7; 95% confidence interval, 1.1–12.6) were significant factors associated with increased ICD frequency. Patients with ICD symptoms were exposed to higher dopamine doses than those without them (1.6 ± 0.1 vs 1.0 ± 0.1 daily-defined doses; P < 0.001). A dose-response pharmacodynamic model disclosed a significant nonlinear dose-response relationship between dopamine agonists and frequency of ICD symptoms (P < 0.01). ConclusionsImpulse-control disorder symptoms were more frequent in the patients with PD than in the poststroke patients with PD. Impulse-control disorder symptoms were related to younger age and exposure to monoaminooxidase-B inhibitors, and showed a nonlinear dose-response relationship with dopamine agonists.

Factors related to orthostatic hypotension in Parkinson's disease.

INTRODUCTION Orthostatic hypotension (OH), a frequent feature of Parkinsons disease (PD) can contribute to falls and is usually related to the disease itself and/or to drugs. OBJECTIVES To explore factors related to OH and to assess the concordance between abnormal blood pressure (BP) fall after standing and the presence of orthostatic symptoms. METHODS Non-demented, non-operated idiopathic PD out-patients were questioned about the presence of orthostatic symptoms. Afterward, BP was measured 5-min after lying down and for 3-min after standing up. OH was defined as systolic and/or diastolic BP fall ≥ 20 and/or 10 mmHg after standing. Patients were further evaluated by the Unified PD Rating Scale (UPDRS) and their medications were recorded. RESULTS 103 patients were included in this study (mean age = 66 ± 1 years, mean disease duration = 9 ± 1 years; mean UPDRS II+III in ON-state = 37 ± 2 points). Forty-one subjects (40%) reported the presence of orthostatic symptoms during the previous week and 38 (37%) had OH according to manometric definition. Independent factors related to OH, as assessed by logistic regression were age >68 years (OR, 95% CI=3.61, 1.31-9.95), polypharmacy (defined as intake of >5 medications, OR = 3.59, 1.33-9.69), amantadine (7.45, 1.91-29.07) or diuretics (5.48, 1.10-54.76), whereas the consumption of entacapone was protective (0.20, 0.05-0.76). The agreement between abnormal BP fall and presence of orthostatic symptoms was poor (kappa = 0.12 ± 0.1, p = 0.23). CONCLUSION OH was significantly related to older age, polypharmacy and amantadine or diuretics intake, while entacapone exposure appeared to reduce the risk of OH. Low concordance between OH and orthostatic symptoms was observed.

Rotigotine transdermal patch for the treatment of Parkinson's Disease.

Rotigotine, a non‐ergot dopamine agonist, has been developed as a novel transdermal formulation. The rotigotine transdermal patch has received EMEA marketing authorization for the treatment of adult patients with early or advanced Parkinson’s disease (PD) or with moderate to severe restless legs syndrome (RLS). FDA originally granted a marketing authorization for early PD, which was later suspended, and is now studying the authorization for RLS. The aim of this review is to review the pharmacokinetics, pharmacodynamics as well as the clinical efficacy and tolerability of the rotigotine transdermal patch in PD. Source material was identified using a PubMed search for the term ‘rotigotine’ and PD. Articles published up to January 2011 or abstract submitted to most relevant international neurology congresses were reviewed. The rotigotine transdermal patch is efficacious for the treatment of PD. Tolerability profile appears to be well within the range of that observed with other non‐ergot dopamine agonists in PD. Application‐site reactions were the most frequent adverse event, and they were considered mild to moderate in the majority of cases. The rotigotine transdermal patch offers a safe and efficacious alternative for the treatment of PD. Further studies should focus on the possibility that continuous dopamine stimulation by means of the transdermal patch has any influence on levodopa‐related motor complications.

Do Parkinson’s disease patients disclose their adverse events spontaneously?

BackgroundUnderreporting of adverse drug reactions is common but has been rarely studied in Parkinson’s disease (PD).ObjectiveTo compare the prevalence of adverse events (AEs) in relation to antiparkinsonian drugs in PD patients using two different data collection methods: patient’s spontaneous reporting versus a predefined investigator-driven structured interview. Secondary objectives were to assess factors related to spontaneous reporting and to compare the rate of AE reporting in PD patients with that of a group of non-parkinsonian post-stroke patients.Study designCross-sectional study.PatientsAmbulatory, cognitively intact PD or post-stroke outpatients.InterventionsNone.Outcome measuresPatients were first asked by means of an an open question to disclose any unpleasant effects in connection with their current medications that had occurred during the previous week. Afterwards, a predefined questionnaire listing the most common AEs known to be related to antiparkinsonian drugs was used to question the same patients in a systematic manner about the presence of any AE during the same week. Chronological and semiological criteria were used to classify the reported AEs as “unrelated” or “possibly/plausibly related” to the antiparkinsonian treatment.ResultsA total of 203 PD and 52 post-stroke patients of comparable age and sex were recruited. Eighty-five PD and five post-stroke patients reported spontaneously at least one AE (42 vs. 10%, p < 0.01), while 203 PD and 47 post-stroke patients reported at least one AE following the structured questionnaire (100 vs. 90%, p < 0.001). In PD patients, there were a total of 112 spontaneously reported AEs as compared with 1,574 according to the structured questionnaire (7%). Spontaneous disclosure of AEs was associated with experiencing >2 AEs [OR = 1.2 (1.1–3.2)], logistic regression). Seventy-four percent of PD patients had ≥1 AE possibly/plausibly related to antiparkinsonian drugs.ConclusionsResults showed that only 7% of AEs were reported spontaneously by patients, thus underscoring the importance of systematically asking about AEs in PD patients.

Pramipexole for the treatment of early Parkinson’s disease

Pramipexole is a nonergolinic dopamine agonist, with high affinity for the D2 subfamily of dopamine receptors. Pramipexole is efficacious for the symptomatic treatment of early Parkinson’s Disease (PD) and its early use, before that of levodopa can delay the emergence of levodopa-related motor complication. Dosage should be increased gradually from a starting dose of 0.375 mg/day up to a maximum of 4.5 mg/day in equally divided doses taken three times per day with pramipexole immediate-release or equivalent daily dosages once-daily with pramipexole extended-release. Pramipexole can also improve depressive symptoms and possibly health-related quality of life in PD. Nonetheless, its use is not devoid of tolerability problems. While peripheral adverse drug reactions, such as nausea, vomiting or orthostatic hypotension, can be effectively treated and usually pose few problems to most patients, neuropsychiatric events can seriously limit the use of pramipexole in some cases. Indeed, excessive daytime somnolence, impulse-control disorders, hallucinations or delusions can severely affect patients, causing important personal or social handicap. Patients should be informed about the risk of such neuropsychiatric complications and their presence should be actively detected at each consultation. More effort will have to be put into further studying the risk–benefit ratio of pramipexole and other dopamine agonists in the treatment of early PD.

Clinical Effects of a 6-Month Treatment Course of Ibandronate, Vitamin D, and Calcium in Postmenopausal Women from Central America: Results of a Multinational, Prospective Pilot Study

Background/Aims: To explore the effects of ibandronate plus a supplementation of vitamin D and calcium on bone mineral density (BMD) and health-related quality of life (HRQoL) in a sample of postmenopausal women from Central America. Secondarily, factors related to the magnitude of improvements in BMD after treatment were investigated. Methods: Postmenopausal women with idiopathic osteoporosis or at risk of developing it, who were going to start treatment with ibandronate 150 mg once a month plus daily supplementation with vitamin D 400-800 IU and calcium 500-1,000 mg, were followed up for 6 months. BMD, HRQoL (mini-Osteoporosis Quality of Life Questionnaire), and treatment adherence (Morisky scale) were studied before and after treatment. Results: Four hundred and twenty-five women were assessed at baseline, and 308 (72%) were reassessed at month 6. Lumbar spine, proximal femur, and hip BMD increased by 3.35 ± 0.75, 1.88 ± 0.50, and 2.75 ± 0.32%, respectively (p < 0.001 for all). HRQoL total score and emotional functioning, symptoms, physical function, and leisure subscores improved by 26-49% (p < 0.01 in all cases). Lower body mass index, younger age at menopause, use of corticoids, and higher adherence were significantly and independently associated with a greater improvement in lumbar spine BMD (logistic regression). Conclusion: Improvements in BMD and HRQoL after ibandronate, vitamin D, and calcium were observed in patients from Central America, which should be confirmed by double-blind, randomized, controlled trials. Lack of adherence to ibandronate was related to worse outcomes, thus highlighting the need for work on this issue with patients on treatment.

Diagnosis and Treatment of Orthostatic Hypotension in Parkinson's Disease

Orthostatic hypotension (OH) is a frequent comorbidity affecting between 23 and 38% of Parkinsons disease (PD) patients. Several pieces of evidence suggest that OH is related to faster cognitive decline and more frequent falls, and has been also connected to increased mortality. OH can be arbitrarily defined as a drop of systolic and/or diastolic blood pressure of 20 or 10 mmHg or more in the first three minutes after passing from decubitus to an upright position. Till test appears to be the most reliable tool for assessing the orthostatic response. On the other hand, the standing test and evaluation of orthostatic symptoms should be regarded as screening tests. The key physiopathological aspect of OH is an altered baroreflex function resulting from cardiac and vascular sympathetic denervation. Nonetheless, OH can be aggravated by heat, alcohol consumption or by drug treatments, such as antihypertensives, dopamine agonists or amantadine. Treatment should begin with re-considering drug treatments. After treatment is optimized, non- pharmacological measures may be employed. Drugs treatment should be reserved for patients in whom other strategies have failed. Midodrine and fludrocortisone are the most frequently used treatments, even though evidence about their efficacy and safety is weak. Midodrine has a shorter duration of action and thus avoidance of evening dosing may help keep nocturnal blood pressure dipping intact. Promising alternatives may include droxidopa and fipamezole.