Orthostatic Hypotension and Antiparkinsonian Drugs: A Systematic Review and Meta-analysis

Background Orthostatic hypotension (OH) is multifactorial in Parkinson’s disease (PD). Antiparkinsonian medication can contribute to OH, leading to increased risk of falls, weakness and fatigue. Methods We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of antiparkinsonian drugs associated with OH as an adverse effect, compared to placebo. We searched EMBASE, MEDLINE and Web of Science databases until November 2020. Analysis used fixed-effects models and the GRADE tool to rate quality of evidence. Meta-analysis was performed if 3 or more studies of a drug group were available. Results Twenty-one RCTs including 3783 patients were included comparing 6 PD drug groups to placebo (MAO-B inhibitors, dopamine agonists, levodopa, COMT inhibitors, levodopa and adenosine receptor antagonists). OH was recorded as an adverse event or measurement of vital signs, without further specification on how this was defined or operationalised. Meta-analysis was performed for MAO-B inhibitors and dopamine agonists, as there were 3 or more studies for these drug groups. In this analysis, compared with placebo, neither MAO-B inhibitors or dopamine agonists were associated with increased risk of OH, (OR 2.28 [95% CI:0.81–6.46]), (OR 1.39 [95% CI:0.97–1.98]). Conclusions Most studies did not specifically report OH, or reporting of OH was limited, including how and when it was measured. Furthermore, studies specifically reporting OH included participants that were younger than typical PD populations without multimorbidity. Future trials should address this, for example,, by including individuals over the age of 75, to improve estimations of how antiparkinsonian medications affect risk of OH.

Impulse control disorders in Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterised by typical motor symptoms and a range of non-motor symptoms, among which impulse control disorders, defined by an inability to resist temptations, impulses or urges, despite them being potentially harmful to the patient or caregivers, are gaining an increasing research interest. The most common compulsive activities include pathological gambling, hyper-sexuality, compulsive buying, and binge eating. The prevalence of impulse control disorders varies greatly depending on the country where the study was conducted, probably due to cultural and socioeconomic factors or the research methods used. Non-ergotamine dopamine agonists, and to a lesser extent highdose L-dopa and other antiparkinsonian drugs, are considered to be major risk factors for the development of impulse control disorders. Young age of patients, male gender, and early age of disease onset also increase the risk of developing this type of disorder. A probable cause of impulse control disorders is a state of dopaminergic overstimulation within the mesolimbic pathway and frontal-striatal circuit. The management of impulse control disorders is particularly challenging in view of the possible worsening of motor symptoms. The primary strategy remains dose reduction, discontinuation or switching from a dopamine agonist to another drug. If this type of intervention has failed, it is advisable to add atypical antipsychotics or antiepileptic drugs. Because of the low detection rate of impulse control disorders and their potentially devastating impact on patients’ personal and family lives, every clinician managing patients with Parkinson’s disease should be particularly vigilant for the presence of such disorders.

Antiparkinsonian drugs as potent contributors to nocturnal sleep in patients with Parkinson’s disease

Objective To clarify whether antiparkinsonian drugs contribute to nocturnal sleep disturbances in patients with Parkinson’s disease (PD). Background Although the major antiparkinsonian drugs L-dopa and dopamine agonists (DAs) have been found to affect sleep, little is known about the effects of specific drugs on sleep in PD patients. Methods The study participants consisted of 112 PD patients (median age 72.5 years [inter-quartile range: IQR 65–79]; mean disease duration 8.44 years [standard deviation: 7.33]; median Hoehn and Yahr stage 3 [IQR 2–3.75]) taking one of three types of non-ergot extended-release DAs (rotigotine 32; pramipexole 44; ropinirole 36) with or without L-dopa (median daily total dosage of antiparkinsonian drugs 525.5 mg [IQR 376.25–658] levodopa equivalent dose [LED]). Participants were assessed using the PD Sleep Scale-2 (PDSS-2). Results For the whole PD patient cohort, the PDSS-2 sleep disturbance domain score and the scores for item 1 assessing sleep quality and item 8 assessing nocturia were positively correlated with daily total dosage of antiparkinsonian drugs and dosage of L-dopa, but not with the dosage of DAs. Sub-analysis according to DA treatment revealed that DA dosage was not correlated with item 1 or 8 score in any of the subgroups. The LED ratio of rotigotine to the total dosage of antiparkinsonian drugs was inversely correlated with the item 1 score. Conclusions These data suggest that antiparkinsonian drugs, in particular L-dopa, adversely affect nocturnal sleep in PD patients, especially in terms of sleep quality and nocturia. Thus, adjusting both the total dosage of antiparkinsonian drugs and the dose-ratio of L-dopa might be key actions for alleviating poor sleep quality in patients with PD. Among DAs, we found a clear positive correlation between the dose-ratio of rotigotine and sleep quality. Thus, partial L-dopa replacement with rotigotine could improve sleep quality in patients with PD.

Profile and frequency of antiparkinsonian drugs adverse reactions: a systematic review and meta-analysis

Objective: to assess the predictors and prevalence of adverse drug reactions (ADRs) associated with antiparkinsonian drugs.Materials and methods. 18 clinical studies and randomized controlled trials were included in the analysis. We combined all registered ADRs for each drug and made direct comparisons with odds ratio (OR) and 95% confidence interval (95% CI) calculation.Results and discussion. Levodopa/benserazide (LB) had the best safety profile among levodopa drugs. Levodopa/carbidopa (LC) compared with LB was associated with more frequent development of nausea (OR=2.8; 95% CI: 1.51–5.21), aggravation of parkinsonism (OR=4.44; 95% CI: 2.12–9.28) and dizziness (OR=3.32; 95% CI: 1.5–7.33; p=0.002). Piribedil had the lowest number of ADRs among dopamine receptor agonists. Dizziness was more common with pramipexole and ropinirole than with levodopa (OR=1.82; 95% CI: 1.21–2.74 and OR=1.65; 95% CI: 1.11–2.44 respectively). Increased daytime sleepiness and peripheral edema have also been associated with pramipexole. Arterial hypertension was present in 9.6% of patients prescribed with piribedil. Amantadine compared with pramipexole was associated with a higher risk of hallucinations (OR=2.27; 95% CI: 1.24–4.12) and constipation (OR=2.40; 95% CI: 1.14–5.05). Patients prescribed with selegeline had higher odds of dizziness (OR=3.40; 95% CI: 1.76–6.55) and hallucinations (OR=4.30; 95% CI: 1.83–10.09) compared to rasagiline.Conclusion. Based on the results, we propose a diagram of the relationship between ADRs and their frequency with antiparkinsonian drugs. We hope that the study will find clinical application and allow neurologists to consider the effectiveness and the expected risks of ADRs in the treatment of PD.

Secondary parkinsonism and normal pressure hydrocephaly because of cranioencephalic trauma: a case report

Context: Normal Pressure Hydrocephalus (NPH) occurs due to the quantitative imbalance of cerebrospinal fluid (CSF), changes in absorption or drainage. It shows idiopathic or secondary etiology. Head trauma (TBI) — which causes brain and/or arachnoid granulations fibrosis and inflammation — impairs CSF reabsorption and induces accumulation in the ventricular system. The diagnosis of sNPH was based on a conjunction of symptoms (e.g.: urinary incontinence, dementia, and gait impairment) and imaging studies. Among the treatments with significant clinical improvement, there are ventriculoperitoneal shunt (VP) and tap test. Case report: FAR, a 74-year old man who was diagnosed with parkinsonian syndrome after 6 months of TBI, showed stiffness, bradykinesia and tremor at rest. In addition, he had CT and Skull MRI. Previous studies suggested PNH. Drug therapy with an optimized dose of Levodopa + Benserazide was established. However, it has shown an unsatisfactory response to antiparkinsonian drugs. Hence, he was submitted to the tap test, obtaining functionality and gait reversion as well as cognitive deficits regression. Those results still remained four weeks after the medical procedure. Conclusions: The work aims to emphasize the importance of a positive tap test response as well as early diagnosis and treatment in the outcome of the morbidity.

Medications associated with development of drug-induced depression

More than 60 % of all depressive syndromes are reactive depression, which occurs in response to internal and external influences. One of the variants of reactive depression is drug-induced (drug-induced) or iatrogenic depression, which is a possible side effect of a number of medications. Depressogenic effect is described in both psychotropic and somatotropic drugs. Depressions that occur when using psychotropic drugs are most often associated with the duration of administration and large doses of the drug. Some antihypertensive, antiarrhythmic, hypolipidemic drugs, antibiotics, hormones, antiparkinsonian drugs and antineoplastic agents are most often mentioned in the series of somatotropic drugs that have a depressogenic effect. Drug-induced depression is one of the most controversial issues. this article presents a systematization of available literature data on depression associated with taking various drugs.

Pattern of adverse drug reactions occurring at department of neurology of a tertiary care hospital in India

Background: The objective of the study was to study the pattern and trends of adverse effects of drugs used in department of neurology in a tertiary care hospital.Methods: A prospective, observational study was carried out for a duration of 12 months from November 2018 to October 2019 at Department of Neurology and Department of Pharmacology and Therapeutics, G.S.V.M. Medical College, Kanpur after getting an approval from institutional ethical committee. Data was collected by analyzing OPD prescription slip, treatment charts and investigation reports. All relevant information regarding adverse drug reactions (ADRs) were collected as per norms of Indian Pharmacopoeia commission (IPC).Results: During the study period, a total of 130 ADRs reported. Most of the ADRs were reported due to antiepileptic drugs followed by antiparkinsonian drugs. Dizziness was the most frequent ADR reported. Most of the ADRs were reported due to phenytoin. Other ADRs observed were drowsiness, nausea/vomiting, weakness, joint pain, dyskinesia.Conclusions: Most of the ADRs were due to anti-epileptic drugs. Most of the reactions were of mild severity.