Validity and reliability of the Portuguese version of the Epilepsy Medication Treatment Complexity Index for Brazil

Epilepsy & Behavior 21 (2011) 467–472

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Epilepsy & Behavior j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / ye b e h

Validity and reliability of the Portuguese version of the Epilepsy Medication Treatment Complexity Index for Brazil Carla Maria Maluf Ferrari a, c,⁎, Luiz Henrique Martins Castro a, Cristina Helena Costanti Settervall a, b, Rosimary Maria de Moura a, Pollyana Aurichio Coutinho c, Iolanda Eiko Shirota Oshiro c, Roseane Batista Alves c, Regina Marcia Cardoso de Sousa b a b c

Department of Neurology, Hospital das Clinicas da Faculdade de Medicina de São Paulo, São Paulo, Brazil Nursing School of the University of São Paulo, São Paulo, Brazil Centro Universitário São Camilo, São Paulo, Brazil

a r t i c l e

i n f o

Article history: Received 20 January 2011 Revised 14 April 2011 Accepted 17 April 2011 Available online 12 June 2011 Keywords: Epilepsy Complexity Treatment Ambulatory care

a b s t r a c t We evaluated the reliability and validity of a Brazilian-Portuguese version of the Epilepsy Medication Treatment Complexity Index (EMTCI). Interrater reliability was evaluated with the intraclass correlation coefficient (ICC), and validity was evaluated by correlation of mean EMTCI scores with the following variables: number of antiepileptic drugs (AEDs), seizure control, patients’ perception of seizure control, and adherence to the therapeutic regimen as measured with the Morisky scale. We studied patients with epilepsy followed in a tertiary university-based hospital outpatient clinic setting, aged 18 years or older, independent in daily living activities, and without cognitive impairment or active psychiatric disease. ICCs ranged from 0.721 to 0.999. Mean EMTCI scores were significantly correlated with the variables assessed. Higher EMTCI scores were associated with an increasing number of AEDs, uncontrolled seizures, patients’ perception of lack of seizure control, and poorer adherence to the therapeutic regimen. The results indicate that the Brazilian-Portuguese EMTCI is reliable and valid to be applied clinically in the country. The Brazilian-Portuguese EMTCI version may be a useful tool in developing strategies to minimize treatment complexity, possibly improving seizure control and quality of life in people with epilepsy in our milieu. © 2011 Elsevier Inc. All rights reserved.

1. Introduction Epilepsy is one of the most common chronic neurological diseases. Antiepileptic drugs (AEDs) are the mainstay of treatment [1]. International League Against Epilepsy (ILAE) guidelines consider that the goal of epilepsy treatment with AEDs is to improve patients’ quality of life, maintaining them, whenever possible, seizure free, preferably on AED monotherapy, with minimal impact of medication side effects [2]. Many patients diagnosed with epilepsy are treated successfully with a single AED. Patients who do not achieve seizure control with AED monotherapy may need polytherapy to achieve better or complete seizure control. Patients with difficult-to-control epilepsy are usually placed on a complex therapeutic regimen, with multiple AEDs, on different dosing schedules. In this context, patients are required to incorporate a very complex medication administration routine into their day-to-day lives [3]. Medication regimen complexity includes number of AEDs and pills taken, number of units per dose, total number of doses per day, and special requirements regarding ⁎ Corresponding author at: Department of Neurology, Hospital das Clinicas da Faculdade de Medicina de São Paulo, São Paulo, SP, Brazil. Fax: + 55 11 5093 7574. E-mail address: [email protected] (C.M.M. Ferrari). 1525-5050/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2011.04.054

medication ingestion, such as interaction with meals or need to crush pills [4]. The Epilepsy Medication and Treatment Complexity Index (EMTCI) [5] is a validated tool specifically designed to address therapeutic complexity in adult patients with epilepsy. It is a modification of the Medication Complexity Index (MCI). EMTCI was originally developed in the United States and was shown to have high reliability and validity, as assessed with psychometric analyses including test–retest reliability, criterion validity, and construct validity. The EMTCI is a four-section questionnaire that assesses general information about medication, medication administration frequency, and special directions and actions to ensure correct medication intake. Scores for the frequency of administration, special instruction, and administration action sections are obtained by summing the points within the section. According to the authors’ instructions, no scores are attributed to items in the first section, which include name of the medicine, number of different medications or treatments in the regimen, number of pills of each drug taken per day, and number and strength (milligrams) of pills taken for each dose. The EMTCI is calculated by adding the scores of the second, third, and fourth sections of the instrument. For patients on a monotherapy regimen, this sum represents their total regimen complexity score. For patients

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on polytherapy with two or more AEDs, the total regimen complexity score is generated by adding the total scores for each prescribed drug for all drugs in the regimen. Information provided by this questionnaire assesses treatmentrelated issues, as well as adherence to the therapeutic regimen. According to the authors, taking the prescribed medication implies taking the correct medicine and proper dose at the right time, as well as following specific instructions, such as preparing the medication or taking it, for example, on an empty stomach, during meals, or on alternate days [5]. The relevance of therapeutic regimen complexity to treatment adherence is well established, not only in newly diagnosed individuals, but also in patients on chronic treatment for many years [4,6–8]. A study that analyzed 661 patients with epilepsy treated for 10 years showed a relationship between missed medication doses and seizure occurrence. This study also demonstrated that therapeutic regimen complexity leads to missed medication doses and increased probability of seizure occurrence [7]. Treatment adherence is related not only to treatment regimen complexity, but also to patients’ perception of disease severity and to symptom frequency [7,8]. Taking into consideration the specificity of the EMTCI in assessing the complexity of therapeutic regimens in patients with epilepsy, as well as the absence of a similar tool in our milieu, the authors translated and adapted the questionnaire to the Brazilian cultural setting, after obtaining written consent from one of the original authors. Translation and adaptation procedures were based on Beaton and co-workers’ recommendations [9]: translation into Brazilian-Portuguese, back-translation into English, evaluation of the equivalence to the original and back-translated versions, and the pretest. On completion of those procedures, we analyzed the psychometric properties of the Brazilian-Portuguese version of the EMTCI. In the validation process, we evaluated the relationship between therapeutic regimen complexity and number of prescribed drugs, measures of treatment adherence and seizure control, as well as patients’ perception of seizure control.

2. Methods To analyze the psychometric properties of the tool, we administered the Brazilian-Portuguese EMTCI version to patients followed in an outpatient clinic specializing in the treatment of epilepsy, in a tertiary referral university-affiliated hospital in São Paulo, Brazil. Participants fulfilled the following eligibility criteria: diagnosis of epilepsy according to ILAE criteria [10], age ≥18 years, independence in activities of daily living, and absence of major cognitive disorders or active psychiatric disease. After agreeing to participate, all subjects signed the informed consent form approved by the local institutional review board (Ethics Committee for Research Project Analysis, CAPPesq, Process No. 0210/09).

2.2. Psychometric analysis 2.2.1. Reliability We used interrater reliability evaluation to assess reliability. We compared EMTCI scores obtained simultaneously by the same subject by two independent trained observers. This procedure allowed analysis of the degree of agreement between raters or of performance of two raters in simultaneously registering the same answers. A total of 30 patients with epilepsy were included in this evaluation. The interrater reliability for the EMTCI was estimated by using the intraclass correlation coefficient (ICC). A reliability estimate was computed for each of three sections—medication frequency, special instructions, and administration actions—as well as for the total score. The ICC ranges from 0 to 1. ICCs b0.3 were classified as low, ICCs b0.6 but ≥0.3 as moderate, and ICCs ≥0.6 but b0.9 as high, according to Callegari Jacques’ criteria [11]. 2.2.2. Validity We used construct validation to assess the validity of the tool in a sample of 385 patients with epilepsy. This method is based on the principle that to prove the construct validity of an instrument, it is necessary to determine whether instrument responses are associated with theoretically relevant concepts. We tested validity by correlating the patients’ EMTCI total scores with the following variables: number of prescribed AEDs, seizure control, patients’ perception of seizure control, and treatment adherence. In this assessment, patients who required more complex regimens were expected to be more likely to take multiple medications to control their seizures. These more complex treatment regimens increase the burden of taking medications and are associated with lower treatment adherence. In addition, people with complex treatment regimens have more difficulty managing seizures. Seizures were considered controlled if patients had been seizure free for a minimum of 6 months before the interview. To evaluate patients’ perception of seizure control, we used a 3-item Likert scale: controlled, not always controlled (includes less frequent and less severe seizures), and not controlled. The Morisky test was used to assess the degree of adherence to the therapeutic regimen [12]. It is a simple four-question questionnaire that evaluates nonadherence behavior. Adherence was classified as high (if the four questions are answered “no”), medium (if one or two questions are answered “yes”), and low (if more than two questions are answered “yes”). To assess construct validity, the association between EMTCI scores and the other variables (number of AEDs, seizure control, patient's perception of seizure control, and Morisky test) was assessed. After data were tested for normal distribution (Anderson–Darling test [13]), analysis of variance (ANOVA) was used to test these associations [14]. The significance level was set at P b 0.05. 3. Results 3.1. Reliability

2.1. Administration of the Brazilian-Portuguese version of the EMTCI The Brazilian-Portuguese version of the EMTCI was administered to patients by trained examiners, in a personal interview in the office. The interviewer went over each item of the questionnaire, completing all four sections of the tool, regarding: general medication information (first section), frequency of administration (second section), special instructions (third section), and administration actions (fourth section). In line with the authors’ instructions [5], a score was calculated for each section and for each questionnaire, and one questionnaire was completed for each medication prescribed. If a patient took more than one medication in his or her regimen, a total regimen score was generated by adding the total scores for all drugs in the regimen.

Average age of participants in the reliability test (n = 30) was 36.6 ± 14.4 years, 50% were female, 60% were single, 30% were married, and 10% were widowed or divorced. Regarding education level, 13.3% of the patients had up to 4 years of education years (fundamental education, level I), 10% had up to 8 years of education (fundamental education, level II), 60% had up to 11 years of education (high school), and 16.7% had at least some college education. Slightly fewer than half of these participants (46.7%) were employed. In the sample, 73.3% had focal symptomatic epilepsy (of whom 20.0% had temporal lobe epilepsy and 40.0% had mesial temporal sclerosis). Most of the participants (66.7%) were on a polytherapy regimen containing two to four AEDs. In the sample used to assess reliability (n = 30), the mean EMTCI score was 17.6 (SD = 8.5, range = 4–34.0). Interrater reliability ICCs

C.M.M. Ferrari et al. / Epilepsy & Behavior 21 (2011) 467–472 Table 1 Results of interrater reliability assessments of the Brazilian-Portuguese version of the EMTCI.

Frequency of administration Special instructions Administration actions Total score

Intraclass correlation coefficient

95% Confidence interval

0.999 0.721 0.935 0.988

0.998–0.999 0.492–0.857 0.868–0.969 0.975–0.994

ranged from 0.721 to 0.999, indicating high or very high reproducibility (Table 1). 3.2. Validity Validity testing included 385 patients with epilepsy. Participants’ ages ranged from 18 to 76 years (mean = 39.7 ± 12.6). In this sample, 53.5% were women, 31.9% were single, 22.6% were widowed or divorced, 12.0% had some college education, and 37.9% were employed (6.5% self-employed). With respect to epilepsy syndrome classification, 79.5% had focal symptomatic epilepsy (54.5% had temporal lobe epilepsy and 34.5% mesial temporal sclerosis), 8.8% had focal cryptogenic epilepsy, 9.9% had generalized idiopathic

Table 2 Demographics, number of antiepileptic drugs antiepileptic medications, seizure control, perceptions of seizure control, and treatment adherence data for patients who took part in the process of validation (n = 385). Age ≥18 but ≤30 ≥31 but ≤45 ≥46 but ≤60 ≥60 Mean (SD) 95% CI [range] Gender Male Female Marital status Married Single Widowed or divorced Education Level Fundamental (level 1) Fundamental (level 2) High school College Occupation Employed Self-employed Disability benefits Retired Unemployed Never worked Student Homemaker Number of AEDs 1 2 3 4 5 Seizure control Controlled Not controlled Patient's perception of seizure control Controlled Not always controlled Not controlled Morisky scale High adherence Medium adherence Low adherence

111 (28.8%) 155 (40.3%) 97 (25.2%) 22 (5.7%) 39.7 (12.57) 38.4–40.9 [18–76] 179 (46.5%) 206 (53.5%) 175(45.5%) 123(31.9%) 87 (22.6%) 27 (7.0%) 81(21.0%) 231 (60.0%) 46 (12.0%) 121 (31.4%) 25 (6.5%) 31 (8.1%) 60 (15.6%) 102 (26.5%) 9 (2.3%) 9 (2.3%) 28 (7.3%)

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Table 3 Association between mean scores on the Brazilian-Portuguese version of the EMTCI and age, gender, marital status, education level, and occupation (n = 385). N

Age b30 ≥31 but ≤45 ≥46 but ≤60 N60 Gender Male Female Marital status Married Single Widowed/divorced Educational level Fundamental (level 1) Fundamental (level 2) High school College Occupation Employed Self-employed Disability benefits Retired Unemployed Never worked Student Homemaker a

Pa

EMTCI Mean

SD

95% CI

Min–max

111 155 97 22

14 15.5 14.9 12.3

8.63 7.68 7.71 7.67

12.4–15.7 14.2–16.7 13.3–16.4 8.9–15.7

2–44 3–39 3–40 3–30

0.243

179 206

14.9 14.5

8.05 7.94

13.7–16.1 13.5–15.6

3–44 2–40

0.644

175 123 87

14.9 14.1 15.2

7.96 8.35 7.52

13.8–16.1 12.6–15.6 13.6–16.8

3–40 2–44 3–40

0.531

27 81 231 46

16.0 15.7 13.9 14.2

6.2 8.4 7.0 8.1

13.5–18.5 13.9–17.6 12.4–15.9 11.4–17.0

4–28 3–39 3–33 3–40

0.366

121 25 31 60 102 9 9 28

13.9 12.8 17.5 13.9 14.6 16.9 16.6 17.9

7.9 7.5 8.02 7.5 7.9 9.7 4.6 9.3

12.5–15.3 9.7–15.8 14.6–20.5 11.9– 15.8 13–16.1 9.4–24.4 13–20.1 14.3–21.5

2–40 4–35 3–40 3–35 3–44 6–31 10–24 5–39

0.073

One way ANOVA.

epilepsy, and 1.8% had generalized cryptogenic epilepsy. As for number of AEDs, 70.6% of the patients were on a two- to five-AED polytherapy regimen; 79.0% had had uncontrolled seizures in the 6 months preceding the interview, 41.0% of the patients considered their seizures as not always or not at all controlled, and 66.2% had medium or low adherence (Morisky test) (Table 2). We did not find ETMCI scores to be statistically significantly associated with age, gender, education level, or occupation (Table 3). The mean EMTCI score was 14.7 ± 8.0 (range: 2–44). Most of the participants (56.6%) had EMTCI scores ≤ 14 points and smaller proportions of participants (6.8%) had EMTCI scores ≥30 (Table 4). The maximum number of AEDs was 5. The maximum EMTCI score was obtained by a participant taking four AEDs (Table 5). Higher EMTCI scores were associated with a larger number of AEDs, uncontrolled seizures (mean EMTCI: controlled, 10.0, vs not controlled, 15.9; P b 0,001), perception of seizure control (mean EMTCI: not always controlled, 16.4, and not controlled, 17.9, vs controlled, 13.2; P b 0.001), and adherence (mean EMTCI: high adherence, 12.2, vs medium adherence, 15.9, P b 0.001, and low adherence, 16.9; P = 0.01) (Table 5, Fig. 1). 4. Discussion

113 (29.4%) 139 (36.1%) 107 (27.8%) 24 (6.2%) 2 (0.5%)

We performed reliability and validation analysis of the BrazilianPortuguese version of the EMTCI, using samples of 30 patients for

81 (21.0%) 304 (79.0%)

Table 4 Results for the Brazilian-Portuguese version of the EMTCI.

227 (59.0%) 102 (26.5%) 56 (14.5%) 130 (33.8%) 233 (60.5%) 22 (5.7%)

EMTCI score

N

%

≥ 2 ≤14 ≥ 15 ≤ 29 ≥ 30 ≤ 44 Total Mean (SD) Range

218 141 26 385 14.7 (8.0) 2–44

56.6 36.6 6.8 100.0

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Table 5 Association between mean scores on the Brazilian-Portuguese version of the EMTCI and number of AEDs, seizure control, patients’ perception of seizure control, and Morisky score (n = 385). N

Number of AEDs 1 2 3 4 5 Seizure control Controlled Not controlled Patients’ perception of seizure control Controlled (a) Not always controlled (b) Not controlled (c) Morisky score High (a) Medium (b) Low (c)

EMTCI

Significance level

Mean

SD

95% CI

Range

Comparison

P

111 139 109 24 2

7.3 13.6 19.8 31.3 29.5

2.7 4.7 5.6 7.1 2.1

6.8–7.8 12.8–14.4 18.7–20.8 28.3–34.2 10.4–48.6

2–14 4–32 9–33 11–44 28–31

1 1 3 4

b 0.001 b 0.001 0.01 0.614 (NS)

81 304

10 15.9

6.2 8.0

8.8–11.5 15–16.8

2–39 3–44

227 102 56

13.2 16.4 17.9

7.5 8.2 8.0

12.2–14.2 14.8–18 15.7–20

2–44 3–40 3–35

a vs b vs c b vs c

b 0.001 0.27 (NS)

130 233 22

12.2 15.9 16.9

6.36 8.36 9.2

11.1–13.3 14.8–17 12.8–20.9

2–33 3–44 4–33

a vs b a vs c b vs c

b 0.001 0.010 0.59 (NS)

reliability analysis and 385 patients for validation analysis, recruited from a tertiary university hospital-based epilepsy outpatient clinic. Both samples of patients in this study had equivalent numbers of men and women, with an average age of 40 years. Although most studies indicate slightly higher epilepsy prevalence and incidence rates in males [15], other studies indicate a slightly higher prevalence of epilepsy in females [16,17], as in the sample of patients who participated in EMTCI validity testing in the present study. With respect to other sociodemographic features, most individuals in this study did not live with spouses or partners. Approximately 37% of the patients either were unemployed, were on disability benefits, or had never held a job. Only a minority of the patients had a college education. A historic overview of epilepsy noted the difficulties faced by patients with respect to employment, forming and maintaining stable marital relationships, and leisure, which may, at least in part, be attributed to stigma [18]. A South Korean study that compared adults (≥ 18 years) affected by epilepsy with unaffected counterparts showed statistically significant differences in schooling, marital status, and professional status. The adults with epilepsy had a larger number of divorced or single people. Additionally, less than half of the people with epilepsy in that study had completed high school or attended college [19]. Regarding epilepsy etiology, our study group showed a predominance of focal symptomatic epilepsy, with a large proportion of patients with temporal lobe epilepsy, specifically temporal lobe epilepsy associated with hippocampal sclerosis. This scenario is

vs vs vs vs

2 vs 3 vs 4 2 vs 5 5 5

P b 0.001

expected in a tertiary referral outpatient clinic catering to a patient population biased toward patients with medically refractory epilepsy. Temporal lobe structures are probably the most epileptogenic brain regions. Temporal lobe epilepsy is the most common focal symptomatic epilepsy syndrome associated with drug refractoriness [20,21]. Patients with refractory epilepsy are expected to take a larger number of prescribed drugs and to have more complex therapeutic regimens [5], which can negatively impact treatment adherence [22]. The patients included in this study represent a sample of patients with very refractory epilepsy. Only 21% of the patients in this study had been seizure free in the 6 months preceding the study. In the current study, about 70% of the patients were receiving AED polytherapy, a finding in agreement with the higher prevalence of medically refractory epilepsy in our study patient population. This figure is higher than in other studies in which approximately 45% of the patients received AED polytherapy comprising two or more drugs [6,23]. The higher prevalence of medically refractory epilepsy in our study cohort is due to the fact that our study was performed at a major tertiary referral center specializing in the treatment of medically refractory epilepsy. On the basis of the EMTCI scores, therapeutic complexity ranged from low, at 2 points, to very high, at 44 points. Patients on monotherapy (29.4%) obtained lower EMTCI scores, with a mean of 7.3 (range: 2–14) points. In a study using the EMTCI that evaluated treatment complexity in 314 adults [4], the mean score was 6.0 points per medicine; 56% of the

Fig. 1. Association of mean scores on the Brazilian-Portuguese version of the EMTCI with treatment adherence, number of antiepileptic drugs, seizure control, and patients’ perception of seizure control.

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patients took more than one AED. EMTCI scores used to validate the original tool ranged from 1 to 15 for each medicine, and patients took an average of two AEDs [5]. The mean EMTCI score in our study was therefore much higher than the scores in these studies. Although a direct comparison cannot be made with these study results, it is conceivable that this is also due to the fact that our sample contained a higher percentage of refractory epilepsy cases. Although the current study participants’ sociodemographic features are comparable to those in other studies of patients with epilepsy [4,5], our patient population was on more complex therapeutic regimens, as evidenced by the high EMTCI scores and the high prevalence of patients receiving AED polytherapy. Treatment adherence as measured with the Morisky scale in our patient population disclosed that the majority (66.2%) of the patients had medium and low adherence. Other studies that have used the Morisky scale to assess treatment adherence in patients with epilepsy have reported similar values for nonadherence to treatment [1,23]. In one of these studies performed in the United States and comprising 50 patients, most were Caucasian (92%), 50% were women, age ranged between 20 and 70 years, 53% had had at least one seizure in the preceding 30-day period, and 48% were receiving AED polytherapy. Low and medium adherence was seen in 58% of the cases [23]. The other study was performed in the United Kingdom and included 54 adult patients. Low and medium adherence was noted in 59% of the cases [1]. Our results showed slightly higher rates for nonadherence, but were still similar to the values in the other studies. In another Brazilian study that used a specifically designed tool to measure adherence, a similar rate of nonadherence (68.5%) was reported in a sample of outpatients with juvenile myoclonic epilepsy, a form of primary generalized epilepsy that usually has a good response to AEDs [24]. The Morisky scale has not been used to assess treatment adherence in patients with epilepsy in Brazil, but it has been used in the measurement of treatment adherence in other chronic diseases [25–27]. Nonadherence in these studies ranged from 28 to 85.8% [26,28,29]. The lowest nonadherence scores (28%) were obtained in a study that evaluated 61 adult patients receiving oral antineoplastic agents [26]. Compared with our results, slightly lower nonadherence scores were obtained by patients with Crohn's disease (50.0%) [25], chronic pancreatitis (64%) [30], diabetes (54%) [31], and ulcerative colitis (54.4%) [25] and other chronic gastrointestinal conditions (63.35 and 63.4%) [25]. Nonadherence was higher among people with arterial hypertension (77% [28] and 85.8% [29]). When testing the reliability of the original EMTCI, the authors obtained, after training and adaptation, ICCs ranging from 0.96 to 0.99. The ICCs for the Brazilian-Portuguese version ranged between 0.72 and 0.99. The lowest scores were obtained for the section on special instructions. This EMTCI section had a low ICC of 0.59 in initial testing carried out in our study. Consequently, all items were reviewed by the evaluators to ensure proper scoring for each item during EMTCI administration. On this basis, the authors recommend a good understanding of the sections on special instructions and administration actions before administering the EMTCI; this was ensured in the current study by retraining of the interviewers. The Medication Regimen Complexity Index (MRCI) [32], another generic tool that assesses therapy complexity, has also been translated and validated into Brazilian Portuguese. The authors analyzed the medical charts of 105 patients with type II diabetes treated with oral hypoglycemic agents or insulin. The full therapeutic regimen for each patient was analyzed, including drugs prescribed for the treatment of other diseases, drugs prescribed for acute conditions, and medications prescribed on an as needed basis. The MRCI was independently administered by two researchers. Reliability, measured with ICCs, was greater than 0.98 for the three sections [32]. In our study, increasing mean EMTCI scores correlated with number of AEDs. Number of AEDs was not the only factor influencing treatment complexity. Some patients taking only one AED obtained EMTCI scores

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as high as and even higher than those of patients taking up to four AEDs (Table 5). Other features of the therapeutic regimen, not only number of AEDs, play an important role in treatment complexity. According to DiIorio et al., less complex therapeutic regimens have been found to be associated with a higher concordance of EMTCI results [5]. The lower EMTCI reproducibility found in the present study may be related to the higher therapeutic regimen complexity observed in our study sample. Despite the therapeutic complexity in our sample, reproducibility was still very high for the following items: frequency of administration, administration actions, and total score. Moreover, even the section on special instructions had high reproducibility, indicating good reliability for use in our milieu. The present study results indicate the validity of the BrazilianPortuguese version of the EMTCI. High scores on the EMTCI, indicating high therapeutic complexity, were related to a higher number of AEDs, uncontrolled seizures, patients’ perception of lack of seizure control, and low and medium adherence to the treatment regimen. A large number of pills increases the complexity of the therapeutic regimen and, hence, the risk of treatment failures [33–36]. High therapeutic complexity in AED regimens may have a major negative impact on treatment adherence [4,5,37]. In other chronic diseases, therapeutic regimen complexity also plays a pivotal role in proper medication intake [25,32,38,39]. Of patients treated with antiretroviral medications in one study, 26.2% identified number of medications as a problem in managing medication intake [39]. Increasing complexity results in patients’ poorer understanding of the therapeutic regimen, leading, consequently, to treatment failure. Poor treatment adherence reduces therapeutic efficacy, resulting in uncontrolled seizures [1]. In our study, people on more complex treatment regimens were more likely to have had seizures in the previous 6 months, which was also corroborated by a perception of poor seizure control. An association between higher EMTCI scores and seizures within the previous year, as well as negative expectations regarding seizure control, was also noted in the validation of the original EMTCI [5]. Our results lend further support to these associations. Patients with refractory epilepsy require more complex therapeutic regimens to control seizures, which, paradoxically, may decrease the adherence to and efficacy of the medication, creating a vicious circle. The challenge for appropriate management of difficult-tocontrol epilepsy is, therefore, to adjust the medication regimen to minimize therapeutic complexity. The EMTCI can serve as a valuable tool in therapeutic regimen adjustment, particularly in difficult-tocontrol epilepsy. The EMTCI may also provide important information to minimize treatment complexity, even when more medication has to be added to the therapeutic regimen. We have demonstrated the reliability and validity of the BrazilianPortuguese version of the EMTCI version. Our data also indicate that the Brazilian-Portuguese version may be a useful tool in assessing the therapeutic complexity of AED regimens in our milieu. The BrazilianPortuguese version of the EMTCI may be useful in clinical practice and in research to identify groups of patients at higher risk for nonadherence to their medication regimens and to evaluate the possible impact of therapy changes on patients with epilepsy; and, possibly, and more importantly, it may serve as a very important tool in developing strategies to increase treatment adherence in people with epilepsy. Use of the EMTCI may positively impact seizure control, leading to improved quality of life in people with epilepsy. References [1] Jones RM, Butler JA, Thomas VA, et al. Adherence to treatment in patients with epilepsy: associations with seizure control and illness beliefs. Seizure 2006;15:504–8. [2] McCorry D, Chadwick D, Marson A. Current drug treatment of epilepsy in adults. Lancet Neurol 2004;3:729–35. [3] Ben-Menachem E, Sander JW, Privitera M, et al. Measuring outcomes of treatment with antiepileptic drugs in clinical trials. Epilepsy Behav 2010;18:24–30. [4] Yeager KA, DiIorio C, Shafer PO, et al. The complexity of treatments for persons with epilepsy. Epilepsy Behav 2005;7:679–86.

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