Juan Medrano

Expert-based drug lists to measure anticholinergic burden: similar names, different results

Background:  Scoring scales such as the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS), and the Anticholinergic Cognitive Burden Scale (ACB) provide an estimation of total anticholinergic burden. Not all the lists include the same drugs, and the points given for certain drugs differ among them. Whether these discrepancies present important differences in the estimation of anticholinergic burden for an individual patient is unknown. Therefore, the aim of this study is to assess agreement among the three scales.

Antipsychotic polypharmacy: a needle in a haystack?

OBJECTIVE The aim of our study was to assess the antipsychotic polypharmacy (APP) prevalence in a psychiatric hospital and to find the supporting evidence for the 10 most prescribed two-drug combinations. Secondarily, how many included clozapine, prevalence in the elderly, high dosage and clinically relevant interactions were also assessed. METHOD Clinicodemographic and computerized prescription data on 29th March 2011 were collected. High dosage was defined as more than 1000 mg of chlorpromazine equivalents (CPZeqs). A t test for unpaired measures was applied to compare means of dosage (CPZeq) and age among patients on APP vs. monotherapy. The χ(2) test was applied to compare proportions of patients on a high dose on APP vs. monotherapy. GraphPad Prism 5 software was used to perform statistical analysis. RESULTS From 201 patients admitted on 29th March, 172 had any antipsychotic prescription. APP prevalence was 47.1%, corresponding almost to 24% of elderly patients. Quetiapine was the drug most prescribed in combination, achieving a prevalence rate of 56.8%. Clozapine was not included in 67% of all combinations. Supporting evidence for two-drug combinations was only found for 6 of the 10 most prescribed. Relevant interactions were found in 12 patients on APP. The mean CPZeq dose and percentage of patients on high dosage were significantly higher in the APP than in the monotherapy group (1162±776.1 mg vs. 455.4±369.3 mg; 54% vs. 9%, respectively; P<.0001). CONCLUSIONS Our study shows that APP was being considered earlier in the management plan than what guidelines recommend. This practice was associated with higher total antipsychotic doses. Until further clinical trials are available, a wise APP practice will require a thoughtful choice of products guided by patients prior history and interaction liability, a proper consent by the patients or their representatives and a careful monitoring of clinical outcomes and emerging side effects in order to avoid indefinite administration of ineffective and potentially harmful combinations.

Confusion Regarding Anticholinergic Burden Measurement

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Aripiprazole and impulse control disorders: higher risk with the intramuscular depot formulation?

Dopamine agonists have been associated with an increased risk of developing impulse control disorders (ICDs). The US Food and Drug Administration (FDA) issued a safety warning in 2016 of a possible association between ICDs and aripiprazole. Recently, one large epidemiological study has confirmed this risk. In the present study, we aim to determine whether the safety signal of ICDs associated with aripiprazole detected by the FDA is replicated in the European pharmacovigilance database (EudraVigilance). We searched for all suspected spontaneous cases of ICDs associated with aripiprazole in EudraVigilance up to 23 February 2017. To assess the association between ICD cases and each dopamine agonist drug, we calculated the proportional reporting ratios (PRRs). Among 4 905 110 events of all types recorded in EudraVigilance, we found 160 cases of ICDs associated with aripiprazole. Aripiprazole fulfilled the criteria to generate a safety signal; PRR (95% confidence interval): 16.39 (13.97–19.24). Notably, the association seemed the strongest for the depot formulation of aripiprazole; PRR (95% confidence interval): 27.13 (17.22–42.75). Our analysis of the data contained in EudraVigilance confirms the safety signal detected last year by the FDA. Interestingly, for the first time, we show that the association seems the strongest for the intramuscular depot formulation of aripiprazole.

Psychopharmacological Issues in Geriatrics

Description: Demographic changes due to improved life expectancy and access to medical care has increased the number of people aged 65 years and beyond. This raises an important new challenge for healthcare professionals. Changes in organ functions, homeostatic mechanisms and receptor responsiveness impair drug distribution, metabolism and excretion, and reduce the effectiveness of medicines among geriatric patients. As a consequence, management of medical regimens is much more challenging in the elderly than in younger adult patients. Elderly patients are also more susceptible than other age groups to certain drugdrug interactions, drug-disease interactions and adverse drug reactions owing to the number of drugs administered.

The burden of constipation in psychiatric hospitals

Abstract Objective: In this study, we aimed to explore the total burden of constipation in our setting by measuring aggregate laxative consumption data and hospital admissions potentially associated with complications of chronic constipation. In addition, we aimed to determine point prevalence of individual laxative use. Methods: This study was carried out across all public psychiatric hospitals in the Basque Country. First, laxative consumption data was obtained for the period from January 2008 to October 2016. Total laxative use was then calculated as the total number of individual daily defined doses (DDD). Second, we analyzed the number of admissions to any public acute health-care hospitals for constipation complications. Third, a cross prevalence study was performed to estimate the point constipation prevalence on December 2016. Results: A mean consumption of oral laxatives around 1 DDD per stay and 1 enema per 100 stays was found. A total of 192 admissions potentially associated with constipation complications were recorded. At the time of the study, approximately half of admitted patients had at least one laxative prescribed. Conclusions: Our study highlights the important burden constipation represents in psychiatric inpatients. Although frequently neglected, it can lead to serious adverse clinical consequences.

Clozapine-Induced Cardiomyopathy in Parkinson's Disease

Cardiomyopathy is a potentially fatal adverse drug reaction (ADR) associated with clozapine in psychotic patients, although it is considered very rare. However, one recent study has reported an incidence of echocardiographic evidence of clozapine-induced cardiomyopathy of 4.65%. This suggests that the real incidence of this reaction might be greatly underestimated. To date, this ADR has been described in relatively young psychotic patients, with higher incidence rates reported in Oceania. But, in addition to its main use in treatment-resistant schizophrenia, clozapine is also considered to be the gold-standard treatment for psychotic symptoms in patients with Parkinson’s disease (PD), disease in which the prevalence and incidence increase nearly exponentially with age. Although some reports have shown that clozapine is seldom used in these patients, 1 study carried in France estimated that approximately 25% of all new clozapine prescriptions were indeed for patients with PD. Concern about this ADR affecting patients with PD in addition to young schizophrenic patients was raised as early as 2000. However, to the best of our knowledge, to date, only one case of myocarditis associated with clozapine has been reported in a patient with PD, whereas no cases of clozapineassociated cardiomyopathy have been reported in individuals with this disease. The Pharmacovigilance Unit of the Basque Country was searched for spontaneously reported cases of cardiomyopathy associated with clozapine among patients with PD in the European pharmacovigilance database (EudraVigilance), which includes ADRs reported from the European Economic Area and, in the case of clozapine (the product of a marketing authorization holder based in Switzerland [Novartis]), notifications from anywhere in the world. First, we performed the search using a standardized MedDRA query for “cardiomyopathy” in the EudraVigilance database until February 2015. Then, cases that involved patients with PD were selected and further analyzed. Patients with PD were identified by analyzing the structured medical history record in EudraVigilance. We identified 5 cases of cardiomyopathy in patients with PD (see Table 1). The mean age of these patients was 70 11.4 years (range, 54–86 years), and all 5 patients were men. Two patients were identified in Ireland, and one patient each was identified in France, Germany, and the United States. The clozapine dose was known in only in 3 patients and was 12.5, 25, and 100 mg/day. Latency was 6 years in one patient and unknown in all others. The ADR was considered severe in all patients, and one patient died. Although it was not possible to establish causality in any of the cases, and important data were lacking, our analysis of the EudraVigilance database indicates that the risk of clozapine-associated cardiomyopathy might not be limited to young schizophrenic patients. The mean age of patients with PD who suffered from cardiomyopathy associated with clozapine was 70 years, compared with a mean age of 33.5 years in the systematic review of published cases affecting young psychotic patients. Recognizing this rare ADR in PD is not easy because of the high prevalence of present comorbidities, such as coronary heart disease, arrhythmia, and congestive heart failure, which make it difficult to identify small increases in these problems and also increase the possibility of a coincidental association. Furthermore, apart from these age-related comorbidities, other important causes of cardiac disease were possible in at least 2 of the 5 reported patients. The second patient was being treated with pergolide, which was withdrawn from the US market in 2007 because of its effect on cardiac valves. The fourth patient had the 22q11 deletion syndrome, which has a known association not only with PD but also with congenital cardiac disease and often requires cardiac surgery. As expected, the mean clozapine dose was considerably lower in patients who had PD compared with psychotic patients (45.8

Pharmacotherapeutic Challenges in Parkinson’s Disease Inpatients

During the natural history of Parkinson’s disease (PD), many patients require hospital admission for medical or surgical problems other than the motor features of PD. Therefore, they are often admitted to non-neurological wards where the staff is unfamiliar with PD management. Among the issues related to hospitalization in patients with PD, drugrelated problems such as inappropriate levodopa timing of administration, the use of contraindicated, centrally acting antidopaminergic drugs and anticholinergic burden remain among the most troublesome.