Symptomatic Pharmacotherapy in ALS: Data Analysis from a Platform-Based Medication Management Programme
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PostScript J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-322938 on 21 April 2020. Downloaded from LETTER during the observation. Riluzole was ALS were provided with a mean number the drug most commonly used (93% of 3.2 symptomatic drugs. However, of patients; n=2219). Symptomatic the number of drugs per patient varied Symptomatic pharmacotherapy drugs were assorted to pharmacological substantially (figure 1D). Furthermore, in ALS: data analysis from a domains and to the attainment of treat- we identified an increasing number of ment goals (figure 1B). An overview prescribed drugs per patient in correla- platform- based medication and ranking of symptomatic drugs are tion to advanced stages of King’s clinical management programme summarised in the online supplementary stages of ALS (figure 1C).4 file 2. Based on the number of patients who received the drug, the following top INTRODUCTION 10 symptomatic medicines were identi- DISCUSSION Although symptomatic medicines fied (in decreasing order): mirtazapine, The symptomatic medication was anal- constitute an important intervention ipratropium bromide, pirenzepine, ysed at specialised ALS centres in in amyotrophic lateral sclerosis (ALS), citalopram, lorazepam, baclofen, metam- Germany collaborating on multidisci- few systematic investigations into drug izole, quinine, fentanyl and tetrahydro- plinary managed care. Data assessment management have been reported so far.1 cannabinol:cannabidiol. Patients with was facilitated by the common use of Furthermore, symptomatic pharmaco- therapy is constantly evolving with an increasing number of drugs being used. Therefore, more detailed information on drug prescription must be obtained to monitor the current standards of care, identify potential shortcomings in drug management and elucidate progress in symptomatic pharmacotherapy. Thus, the aims of the present study were to (i) identify the spectrum of symptom- atic drugs; (ii) rank symptomatic drugs according to their frequency of use; (iii) assign symptomatic drugs to pharmaco- logical domains and (iv) determine the copyright. number of symptomatic drugs per patient. We hypothesised that the pharmacolog- ical spectrum and frequency of use range widely. Furthermore, we supposed that symptomatic drug treatment may vary substantially among patients with ALS and may be highly personalised. METHODS http://jnnp.bmj.com/ A prospective, multicentre, cross- sectional observational study was conducted. The Figure 1 (A) Characteristics of the study participants. (B) Assignment of symptomatic drugs to participants met the following criteria: (1) pharmacologic domains and ranking according to the frequency of use. The number and percentage 2 diagnosis of ALS ; (2) one or more ALS- of patients is shown who received the drug during the course of ALS treatment. Symptomatic drugs related drug prescriptions; (3) participa- were assorted the leading domains of symptomatic drugs: (1) anticholinergic drugs: pirenzepine, tion in a case management programme ipratropium bromide, amitriptyline, atropine, scopolamine, bornaprine, (2) antidepressant drugs: for ALS medication; (4) consent to data mirtazapine, citalopram, amitriptyline, escitalopram, opipramol, dextromethorphan/quinidine, on September 27, 2021 by guest. Protected 3 capture using a digital research platform. agomelatine, venlafaxine, sertraline, trimipramine, duloxetine, paroxetine; (3) antispasmodic drugs: The cohort encompassed patients who had baclofen, tetrahydrocannabinol:cannabidiol, tizanidine, 4- aminopyridine, botulinum toxin, tolperisone; received treatment at nine specialised ALS (4) benzodiazepines: lorazepam, diazepam; (5) non- opioid analgesic drugs: metamizole, ibuprofen, centres in Germany between July 2013 diclofenac, etoricoxib; (6) opioid drugs: fentanyl, oxycodone, tilidine, tramadol, morphine sulfate, and December 2019. Participant’s demo- tapentadol, tramadol, codeine; (7) cramp- reducing drugs: quinine; (8) hypnotic drugs: zopiclone, graphic and clinical data are summarised zolpidem, melatonin; (9) anticonvulsant drugs: pregabalin, gabapentin, carbamazepine; (10) in figure 1A. Detailed methods and the prokinetic and laxative drugs: polyethylene glycol, domeridone, metoclopramide; (11) Parkinson setting of the study are listed in the online drugs: levodopa, rotigotine, pramipexol, ropinirole; (12) broncholytic drugs: acetylcysteine, tyloxapol, supplementary file 1. carbomer, salbutamol, ambroxol; (13) psycholeptic drugs: olanzapine, quetiapine, melperone; (14) overactive bladder drugs: oxybutynin, trospium, butylscopolamine; (15) cholinergic drugs: pyridostigmine. (C) Number of symptomatic drugs per patient in relation to the King’s clinical stage RESULTS of ALS; stage 1=involvement of one clinical region; stage 2=involvement of second clinical region; A cohort of 2392 patients with ALS stage 3=involvement of third clinical region; stage 4=nutritional or respiratory failure. (D) Number of including 7562 prescriptions of ALS- symptomatic drugs per patient. The number of drugs per patient referred to all drugs of any given related medicines was captured. A total patient that were applied during the course of disease. Detailed methods are listed in the online of 1157 patients (48.4%) had died supplementary file 1. n, number of patients; SD, standard deviation. J Neurol Neurosurg Psychiatry Month 2020 Vol 0 No 0 1 PostScript J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2020-322938 on 21 April 2020. Downloaded from a digital management platform that the national variability in legal and social 8Department of Neurology, Technische Universität Dresden, Dresden, Germany allowed for an assessment of ALS phar- frameworks of drug treatment. 9 macotherapy in the largest cohort so far. The high number of medicines per Research Site Dresden, DZNE, German Center for Neurodegenerative Diseases, Dresden, Germany Moreover, this study included patients at patient (mean 3.2 drugs) underlines the 10Department of Neurology, Hannover Medical School, all stages of the disease. In contrast, symp- relevance of symptomatic pharmaco- Hannover, Germany tomatic drugs were previously collected therapy. One fifth of patients requested 11Department of Neurology, University of Ulm, Ulm, in the context of clinical trials or in late- more than four symptomatic drugs. Germany stage ALS.5 6 In this study, we identified The actual frequency of prescriptions Correspondence to Professor Thomas Meyer, about 100 different drugs administered may even higher as some symptomatic Department of Neurology, Center for ALS and other for symptomatic treatment in ALS. This drugs are likely to have been prescribed Motor Neuron Disorders, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany; thomas. meyer@ charite. impressive number may give rise to the outside the platform. Strikingly, the de conclusion that symptomatic pharmaco- number of drugs requested per patient Acknowledgements The authors wish to thank the therapy is highly diverse and variable, ranged widely (range 1 drug to 18 medi- Boris Canessa ALS Stiftung (Düsseldorf), ’Initiative für supposedly an underestimated fact. The cines). Such variability may be due to Menschen mit ALS’ (Berlin) and Bremer ALS Stiftung ranking of drugs revealed striking differ- the different stages of ALS covered with (Bremen), for co- funding this work and for their ences in the frequency of use ranging from this cohort. In fact, the finding of an continuous support. frequently used to rarely applied agents. increasing number of drugs per patient in Contributors TM: contributed to the design, The highest- ranking drugs encompassed advanced stages of King’s clinical stages conceptualisation, writing, data analysis, data agents for the treatment of excessive of ALS is contributing to this notion acquisition and critical revision of the manuscript. DK, AM, TG, UW, JG, RS, JN, AG, AH, RG, SP, OS, JD salivation, depression and/or emotional (figure 1C, online supplementary file 3). and AL: contributed to the data acquisition and lability, spasticity, anxiety, moderate pain Further investigations are of interest to critical revision of the manuscript. BW: contributed and severe pain or dyspnoea, and fascic- correlate classes of symptomatic medi- to the statistical analysis, data analysis and critical ulations (online supplementary file 2). By cines (and distinct drugs) to stages of revision of the manuscript. CM: contributed to the allocating symptomatic drugs to pharma- design, conceptualisation and critical revision of the disease (or to specific symptoms). manuscript. SS: contributed to the writing, statistical cological domains, it becomes even clearer In conclusion, symptomatic drug treat- analysis, data analysis and critical revision of the how these drugs rank (figure 1B). ment was a frequent and ongoing health- manuscript. The data on symptomatic drugs care intervention in the cohort studied. Competing interests TM and CM are founders as prescribed by ALS specialists are Pharmacotherapy in ALS was complex, of the digital management platform ’APST’ and hold intended to provide a broad benchmark individualised and included multiple shares in Ambulanzpartner Soziotechnologie APST of ALS drug management. It may offer GmbH. drugs. Despite its pivotal importance to copyright. support to neurologists and other physi- ALS care, for most of the many symp- Patient consent for publication Not required. cians who seek guidance in symptomatic tomatic drugs, the level of evidence Ethics approval Ethical