Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research
  Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login  
  Home Print this page Email this page Small font sizeDefault font sizeIncrease font size Users Online: 10401       

   Table of Contents      
Year : 2017  |  Volume : 145  |  Issue : 3  |  Page : 264-266

Playing soft, with tough players: Controlling adverse drug effects while tuning antiepileptic drugs, epilepsy & the person

Psychiatric Department, Clinic for Neurology & Psychiatry for Children & Youth, Belgrade, Serbia

Date of Submission17-Aug-2016
Date of Web Publication27-Jul-2017

Correspondence Address:
Dejan Stevanovic
Psychiatric Department, Clinic for Neurology & Psychiatry for Children & Youth, Belgrade
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijmr.IJMR_1388_16

Rights and Permissions

How to cite this article:
Stevanovic D. Playing soft, with tough players: Controlling adverse drug effects while tuning antiepileptic drugs, epilepsy & the person. Indian J Med Res 2017;145:264-6

How to cite this URL:
Stevanovic D. Playing soft, with tough players: Controlling adverse drug effects while tuning antiepileptic drugs, epilepsy & the person. Indian J Med Res [serial online] 2017 [cited 2020 Feb 24];145:264-6. Available from:

Accumulated evidence over the past decades clearly indicates that successful treatment of epilepsy is based on antiepileptic drugs (AEDs). To be considered successful, it has to be an optimally weighted treatment when the efficacy, safety/tolerability and costs of one or more AEDs are calculated individually for each person with epilepsy. Dozens of AEDs were introduced with various positive neuropsychiatric effects and documented effectiveness in epilepsy[1],[2], but also with various adverse effects related to cognition, emotions, behaviour and somatic functions[2],[3],[4]. Epilepsy poses a substantial economic burden for health systems, individuals and their families, with AEDs being one of the major sources of expenditure[5], including their adverse effects[6].

In the study by Joshi et al[7] in this issue, adverse effects, AEDs load, seizure frequency and biochemical alterations were found to be associated with the total number of AEDs prescribed. This study, although limited due to its cross-sectional design, showed us that various adverse effects were associated with number of AEDs rather than frequency of epileptic seizures. It also showed that polytherapy with a combination of three or more AEDs was probably associated with higher adverse effects and lower seizure control compared to both monotherapy and combination of two AEDs. However, no marked relationship of biochemical parameters with different AED regimens was observed. Taken together, the results of this study closely resemble data from randomized controlled trials primarily showing that adults taking AEDs mostly report more than one AED- related adverse effect, with even 83 per cent of people with epilepsy treated with polytherapy reporting two or more adverse effects[3],[8],[9]. In addition, the results agreed with a recent study that documented a considerable adverse effect of a higher drug load on cognition[4]. However, one previous cross-sectional study showed that adverse effects did not differ between monotherapy and polytherapy and did not correlate with AED load, what was considered to be a result of physicians' intervention in individualizing treatment regimens[10].

Here, I would like to reflect upon the ways in which Joshi et al[7] could extend the study in future projects. First, the outcomes of the association of adverse effects and AEDs are shaped throughout the individualized treatment regimen, which should be studied in a follow up approach considering a network of the various factors. Thus, it would be important to evaluate various individual characteristics (e.g., behavioural, cognitive or social), which might be differently linked to adverse effects in monotherapy and polytherapy. The authors studied age, gender and biochemical parameters and the results were more or less the same to the previously reported ones. Second, an important aspect to include is how specific neurocognitive performances in an individual are linked to adverse effects of a particular AED. Different positive and negative cognitive and behavioural effects for AEDs were documented over the past two decades[11], and studying prospectively cognitive functions in relations to adverse effects on individual levels would be important. Third, it was found that individual AEDs independently predicted some specific adverse effects, but not overall high adverse effect burden[3]. Thus, it would be interesting to study how two or more AEDs predict adverse effects in an individual, as well as their interactions in the case of polytherapy. Fourth, studying the severity of epilepsy beyond a simple measure of seizure frequency as linked to individual adverse effects is another necessary consideration. Recent data showed that the excitability levels in neural tissue mattered most when quantifying the outcomes of AEDs[12]. Finally, in the constellation of these various factors, it would be relevant to the study to which extent monotherapy and polytherapy influence the everyday living, whereas adverse effects could negatively affect the quality of life in epilepsy[13],[14].

The second relevant point is that Joshi et al[7] also evaluated the prescribed daily dose (PDD) and defined daily dose (DDD) for each AED included in the treatment regimen as an indicator for the AED load. It was reported that AED load did not have any correlation with the occurrence of adverse effects, although it was observed that the greater the number of prescribed AEDs, the higher the occurrence of adverse effects. This is an important finding for determining whether specific AED therapy is rational and it deserves an analysis of possible factors for these associations reported. There are some conflicting data on AED load and adverse effects; some authors have shown that AED toxicity may be related to total drug load rather than to the number of AEDs administered[6],[15], for example, Canevini et al[10] provided evidence that adverse events did not differ between monotherapy and polytherapy and did not correlate with AED load.

Although these are hypothetical (i.e., research) considerations, but on the other hand, taking a clinical approach might lead us to further extend the research on adverse effects in a patient-centred way to optimize health outcomes in active epilepsy[16]. Dealing with a person suffering from epilepsy in a routine clinical practice is as fine as tuning a violin to play perfectly. The person her/himself, epilepsy and ADEs form a complex neuropsychopharmacological triangle. Epilepsy is 'a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological and social consequences of this condition'[17], while AEDs act by reducing the excitability levels in neural tissue to reduce seizure severity and frequency[3],[4], each of these having a specific pharmacological profile[2]. Thus, we have the person, epilepsy, and the AEDs that might influence each other and each self to various degrees creating a unique predisposition (i.e., variance) at an individual level to develop specific adverse effects. Weighting these aspects with a person with epilepsy or his/her caregivers would be of significant relevance for successful treatment, which should be effective, safe and least-expensive.

   References Top

Talati R, Scholle JM, Phung OJ, Baker WL, Baker EL, Ashaye A, et al. Effectiveness and safety of antiepileptic medications in patients with epilepsy. Comparative Effectiveness Reviews, No. 40. Rockville (MD): Agency for Healthcare Research and Quality (US); 2011. Available from:, accessed on August 16, 2016.  Back to cited text no. 1
Santulli L, Coppola A, Balestrini S, Striano S. The challengesof treating epilepsy with 25 antiepileptic drugs. Pharmacol Res 2016; 107 : 211-9.  Back to cited text no. 2
Kowski AB, Weissinger F, Gaus V, Fidzinski P, Losch F, Holtkamp M. Specific adverse effects of antiepileptic drugs – A true-to-life monotherapy study. Epilepsy Behav 2016; 54 :150-7.  Back to cited text no. 3
Witt JA, Elger CE, Helmstaedter C. Adverse cognitiveeffects of antiepileptic pharmacotherapy: Each additional drug matters. Eur Neuropsychopharmacol 2015; 25 : 1954-9.  Back to cited text no. 4
Allers K, Essue BM, Hackett ML, Muhunthan J, Anderson CS, Pickles K, et al. The economic impact of epilepsy: A systematic review. BMC Neurol 2015; 15 : 245.  Back to cited text no. 5
de Kinderen RJ, Evers SM, Rinkens R, Postulart D, Vader CI, Majoie MH, et al. Side-effects of antiepileptic drugs: The economic burden. Seizure 2014; 23 : 184-90.  Back to cited text no. 6
Joshi R, Tripathi M, Gupta P, Gulati S, Gupta YK. Adverse effects & drug load of antiepileptic drugs in patients with epilepsy: Monotherapy versus polytherapy. Indian J Med Res 2017; 145 : 317-26.  Back to cited text no. 7
Perucca P, Carter J, Vahle V, Gilliam FG. Adverse antiepileptic drug effects: Toward a clinically and neurobiologically relevant taxonomy. Neurology 2009; 72 : 1223-9.  Back to cited text no. 8
Cramer JA, Fisher R, Ben-Menachem E, French J, Mattson RH. New antiepileptic drugs: Comparison of key clinical trials. Epilepsia 1999; 40 : 590-600.  Back to cited text no. 9
Canevini MP, De Sarro G, Galimberti CA, Gatti G, Licchetta L, Malerba A, et al. Relationship between adverse effects of antiepileptic drugs, number of coprescribed drugs, and drug load in a large cohort of consecutive patients with drug-refractory epilepsy. Epilepsia 2010; 51 : 797-804.  Back to cited text no. 10
Aldenkamp A, Besag F, Gobbi G, Caplan R, Dunn DW, Sillanpää M. Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Adverse cognitive and behavioural effects of antiepileptic drugs in children. Epileptic Disord 2016; 18 : S55-S67.  Back to cited text no. 11
Meisel C, Plenz D, Schulze-Bonhage A, Reichmann H. Quantifying antiepileptic drug effects using intrinsic excitability measures. Epilepsia 2016; 57 : e210-5.  Back to cited text no. 12
Baker GA, Jacoby A, Buck D, Stalgis C, Monnet D. Quality of life of people with epilepsy: A European study. Epilepsia 1997; 38 : 353-62.  Back to cited text no. 13
Jovanovic M, Jocic-Jakubi B, Stevanovic D. Adverse effects of antiepileptic drugs and quality of life in pediatric epilepsy. Neurol India 2015; 63 : 353-9.  Back to cited text no. 14
Deckers CL, Hekster YA, Keyser A, Meinardi H, Renier WO. Reappraisal of polytherapy in epilepsy: A critical review of drug load and adverse effects. Epilepsia 1997; 38 : 570-5.  Back to cited text no. 15
Gilliam F. Optimizing health outcomes in active epilepsy. Neurology 2002; 58 (8 Suppl 5) : S9-20.  Back to cited text no. 16
Panayiotopoulos CP. The new ILAE report on terminology and concepts for organization of epileptic seizures: A clinician's critical view and contribution. Epilepsia 2011; 52 : 2155-60.  Back to cited text no. 17


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article

 Article Access Statistics
    PDF Downloaded276    
    Comments [Add]    

Recommend this journal