Safety of Cabergoline for Postpartum Lactation Inhibition or Suppression: A Systematic Review.

This study sought to perform a systematic review of adverse events reported with the use of cabergoline for postpartum lactation inhibition or suppression in women aged 15 to 50. Following registration with PROSPERO (CRD42017049894), a comprehensive search of the Ovid databases Medline, Embase, and CENTRAL, along with PubMed, was conducted from January 1, 1985 to January 25, 2018. All study designs investigating cabergoline use for postpartum lactation inhibition or suppression in women aged 15 to 50 were included. A total of 695 articles were retrieved, and 25 articles were eligible for inclusion. Adverse events were then reported in terms of frequency, with percentages calculated according to the total number of women exposed to the intervention. A bias assessment of the articles was also performed. Among a total of 757 women, 108 adverse events were observed in 96 women (14.2%). The most common adverse events were dizziness (35 of 757), headache (30 of 757), and nausea or vomiting (19 of 757). These events were described as short-lived, self-resolving, and dose dependent. One pharmacovigilance study reported 29 "serious" events from a total of 175 events in 72 case reports, which included thromboembolic and neurologic events. Four case studies specifically addressed the psychiatric population, with one half reporting psychiatric symptoms following administration of cabergoline. In conclusion, this systematic review demonstrates that adverse events were generally benign and tolerable following the administration of cabergoline. However, pharmacovigilance data reveal that vigilance is still needed given the occurrence of rare but serious events.

Ergot and non-ergot dopamine agonists and heart failure in patients with Parkinson's disease.

PURPOSE: Some studies have suggested a potential risk of heart failure in patients with Parkinson's disease receiving dopamine (DA) agonists. However, the results are conflicting. We used VigiBase®, the World Health Organization (WHO) Global Individual Case Safety Reports (ICSRs) database, to investigate a potential signal strengthening of heart failure with DA agonists in Parkinsonian patients older than 45 years. METHODS: A case/non-case (disproportionality) analysis was performed in Vigibase® using ICSRs registered between 1978 and May 2016. The signal of disproportionality was calculated using reporting odds ratios (ROR). In our study, 154 ICSRs of heart failure occurring in 154 Parkinsonian patients (mean age 69.6 years, 51 % women) treated with DA agonists were included. RESULTS AND CONCLUSION: There was a significant signal between occurrence of heart failure and exposure to pergolide or cabergoline in particular and ergot derivatives in general. In contrast, none signal was found for rotigotine, pramipexole, apomorphine, or ropinirole in particular and non-ergot derivatives in general. The present study underlines the importance to prescribe as DA agonists in Parkinsonian patients only non-ergot derivatives, excluding ergot drugs.

Dihydroergotamine affects spatial behavior and neurotransmission in the central nervous system of Wistar rats.

INTRODUCTION: Dihydroergotamine (DHE) is a derivative of an ergot alkaloid used as an antimigraine medication. Nowadays, ergot alkaloids may still endanger the safety of humans and animals as food or medicine pollutants, but the outcomes of long-term DHE administration on the behaviour and neurotransmission remain undescribed. MATERIAL AND METHODS: Adult male Wistar Albino Glaxo rats pre-treated orally with DHE for six weeks were investigated to assess the relationship between concentration of neurotransmitters and behavioural response. The behavioural effects of the drug administered at doses of either 30 µg/kg b.w. (group DHE30, n = 11) or 100 µg/kg b.w. per day (group DHE100, n = 10) were evaluated in the Morris Water Maze. It is known that monoaminergic neurotransmitters (serotonin, noradrenaline and dopamine) in some brain structures (prefrontal cortex, hippocampus, striatum, cerebellum, spinal cord) play a role in the control of cognitive and motor functions. The concentration of neurotransmitters was determined by High Performance Liquid Chromatography (HPLC). RESULTS: Administration of DHE influenced neither the learning processes nor memory in rats. Nevertheless, an increased motor activity of the DHE-administered animals was observed in both the cued and non-cued behavioural tasks. In HPLC examination, changes in the concentration of monoaminergic neurotransmitters and their metabolites were noted in all tested structures, except for the hippocampus. CONCLUSIONS: DHE is able to modulate noradrenergic, serotonergic and dopaminergic neurotransmission that may support the increase in locomotion.

Document of revision and updating of medication overuse headache (MOH). / Documento de revisión y actualización de la cefalea por uso excesivo de medicación (CUEM).

INTRODUCTION: Medication overuse headache is a secondary headache in which the regular or frequent use of analgesics can increase the frequency of the episodes, causing the transition from episodic to chronic headache. The prevalence of medication overuse headache is approximately 1-2%, with higher rates among women aged 30-50 years and with comorbid psychiatric disorders such as depression or anxiety, or other chronic pain disorders. It is important to be familiar with the management of this disease. To this end, the Spanish Society of Neurology's Headache Study Group has prepared a consensus document addressing this disorder. DEVELOPMENT: These guidelines were prepared by a group of neurologists specialising in headache after a systematic literature review and provides consensus recommendations on the proper management and treatment of medication overuse headache. The treatment of medication overuse headache is often complex, and is based on 4 fundamental pillars: education and information about the condition, preventive treatment, discontinuation of the drug being overused, and treatment for withdrawal symptoms. Follow-up of patients at risk of recurrence is important. CONCLUSIONS: We hope that this document will be useful in daily clinical practice and that it will update and improve understanding of medication overuse headache management.

Safety considerations when using non-ergot dopamine agonists to treat Parkinson's disease.

INTRODUCTION: Nonergot dopamine agonists (NEDA) represent an excellent treatment option for Parkinson's disease (PD) patients, in both early and advanced stages of the disease. The post-marketing phase of NEDA has highlighted, though, the occurrence of important long-term adverse events. AREAS COVERED: This review reports recent updates on NEDA adverse events, analyzing neurobiological bases and risk factors of these complications. A literature search has been performed using Medline and reviewing the bibliographies of selected articles. EXPERT OPINION: NEDA represents a very important option in the treatment of PD. Criticisms on their use can be overcome through a better knowledge of these molecules and of the risk factors for adverse events which allow specialists to prevent the occurrence of undesired complications and consent a tailor-based approach. Abbreviations: PD: Parkinson's disease, DA: dopamine agonists, NEDA: non-ergot dopamine agonists, ICD: impulse control disorders, DAWS: dopamine agonist withdrawal syndrome, CYP: Cytochrome P, PK: pharmacokinetic, AUC: area under the curve, HRT: hormone replacement therapy, AV: atrioventricular, HF: heart failure, OH: orthostatic hypotension, RBD: REM behavior disorders, PDP: Parkinson's disease psychosis, DRT: dopamine replacement therapy, DDS: dopamine dysregulation syndrome, MMSE: Mini-Mental state examination, EDS: excessive daytime somnolence.

A systematic review and meta-analysis assessing adverse event profile and tolerability of nicergoline.

OBJECTIVE: To evaluate the safety profile of nicergoline compared with placebo and other active agents from published randomised controlled trials. DESIGN: Systematic review and meta-analysis of nicergoline compared with placebo and other active agents across various indications. DATA SOURCES: MEDLINE, Medline-in-process, Cochrane, EMBASE, EMBASE alerts, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR) and Cochrane Methodology Register (CMR) for all the randomised controlled trials, open-label or blinded, in adults treated with nicergoline. Studies published until August 2013 were included. REVIEW METHOD: 29 studies were included for data extraction. The studies included in this review were majorly from European countries and mostly in cerebrovascular disease (n=15) and dementia (n=8). RESULTS: The treatment withdrawals were comparatively lower in the nicergoline group as compared with the placebo group (RR=0.92; 95% CI 0.7 to 1.21) and other active comparators (RR=0.45; 95% CI 0.10 to 1.95), but the difference was non-significant. Incidence of any adverse events (AEs) was slightly higher (RR=1.05; 95% CI 0.93 to 1.2) while incidence of serious AEs was lower (RR=0.85; 95% CI 0.50 to 1.45) in the nicergoline compared with placebo group. Frequency of anxiety was significantly lower in nicergoline as compared with placebo (p=0.01). Other AEs including diarrhoea, gastric upset, dizziness and drowsiness were less frequent in the nicergoline group when compared with placebo/active drugs, but the difference was non-significant. Frequency of hypotension and hot flushes was slightly higher in the nicergoline group but the difference was non-significant. None of the studies reported any incidence of fibrosis or ergotism with nicergoline treatment. CONCLUSIONS: Nicergoline is an ergot derivative, but its safety profile is better than other ergot derivatives like ergotamine and ergotoxine. This systematic review and meta-analysis suggests that nicergoline has a good safety profile. None of the studies included in this systematic review reported any incidence of fibrosis or ergotism with nicergoline.