Knowledge of the sociodemographic and pharmacological profile of patients with pharmacoresistant epilepsy and factors that can influence them aim to help in the success of the treatment.
Most patients with epilepsy treated at the hospital are low-income people, and according to the literature, these individuals can be exposed to several causes of epilepsy, which can lead to a more serious condition [17]. In addition, still in the economic aspect, the high frequency of crises may be one of the factors that makes it difficult to remain in work activities among the patients in this study. [18]. In this context, the need for social security benefits and multidisciplinary care for such patients is relevant, with emphasis on social assistance to be able to help them in this matter, given the low incidence of retirees [19].
The high prevalence of AED polytherapy is characteristic of patients with pharmacoresistant epilepsy. This implies a complex therapeutic regimen, whose seizure control is achieved by a minority of patients [6]. Although some studies indicate the absence of evidence that polytherapy is more effective than monotherapy, the need for new attempts to control seizures becomes imperative [20].
In this sense, it was observed that as the patient does not have control over the seizures, the seizures can generate an increase in the drug load through the increase of doses in the pharmacotherapy in an attempt to control them (p < 0.05). Added to this fact is the patient's need to use other therapeutic groups that can also contribute to the increase in the drug load and lead to the appearance or increase in the intensity of AE [21]. The evaluation of the patient's drug load can help define the pharmacotherapeutic plan and manage the disease [22].
Still on the difficulty of controlling seizures, it is imperative to consider that some patients with pharmacoresistant epilepsy may benefit from other types of treatment, such as surgical intervention [23]. However, qualitatively, there were spontaneous reports from patients at the time of the interview about their fear of undergoing this procedure.
The therapeutic groups most used for self-medication were analgesics and muscle relaxants, which may be justified by the AE “headache,” prevalent in the LAEP instrument, very common in patients with focal epilepsy [24].
The most prescribed AED found in the study (CLB, LTG, CBZ, TPM, VPA) are consistent with the national guidelines, and partially consistent with international guidelines and other studies, which point to these AED as effective and relatively safe. CLB was the most prescribed AED, probably due to its relatively low tendency to produce sedation and lower incidence of loss of therapeutic effect over time, when compared to other benzodiazepines [25]. Thus, it becomes appropriate for long-term adjuvant therapy in association with other AED, in patients with pharmacoresistant epilepsy [26].
The widespread prescription of second-generation AED such as LTG and TPM is due to the favourable AE profile and pharmacokinetic profile when compared to the first-generation AED [27 – 28], thus they are widely used for the treatment of patients diagnosed with focal and generalized seizures [29].
Other AED options such as LEV, OXC, and GBP, which make up the international guidelines for the treatment of pharmacoresistant epilepsy, were not frequent in our results. Even though LEV and GBP are acquired free of charge by patients through the Brazilian Public Health System (BPHS) [30], their cost to the health system can be considered a limiting factor for acquisition, thus hindering access to these medications.
The BPHS also covers the AEDs that are more difficult to access (LMT, CLB, and TPM) [31] but patients report frequent drug shortages. The lack of regularity in access can directly compromise the family income, cause underuse of the medication, or even lead to the total interruption of treatment [32]. Our numbers show that more than half of patients have access irregularities, evidencing an important limitation of medication policies in Brazil.
It is also noteworthy that there are new AED available on the market, such as perampanel and brivaracetam; these are not offered by the BPHS [30], however they are recommended for the treatment of pharmacoresistant epilepsy in developed countries [32-33]. Thus, restrictions on the use of the antiepileptic drug arsenal may favour therapeutic associations and possibly increase AE [34].
The AE profile is influenced by multifactorial causes, with evidence for the use of AED association and the use of other therapeutic groups [35]. The quantitative analysis of the LAEP identified that 83 (38.4 %) of the patients had a total score equal to or greater than 45 points, thus this value represents a risk of overdose with a possible need for clinical intervention [36]. However, the high frequency of AED associations made it difficult to predict the relationship between the AE and the drug used, since polytherapy makes it difficult to associate the patient's complaint with a specific AED.
Many studies involving pharmacoresistant patients, more frequently present psychiatric and neurological manifestations [37], thus, the use of antidepressants and antipsychotics by patients may be related to this fact. Failure to identify and treat these comorbidities, especially anxiety and depression, can have a major impact on the quality of life of this population [38].
Adherence to pharmacological therapy can determine the success of treatment in patients with epilepsy, which corroborates the profile of patients in this study, where almost half of them did not adhere to treatment and had a greater number of seizures when compared to patients considered adherent to treatment. The literature does not have a consensus on the adherence rate in this population [39], but some studies have reported variations of 40 to 60 % [40-43]. It is noteworthy that better results were expected due to the place of care being a reference centre, part of an economically favoured region, where there are good public and private health systems.
Furthermore, patients with a higher level of education showed greater adherence to treatment (p˂0.05), which may be associated with the ability to follow the pharmacological treatment correctly, as demonstrated by the MedTake result of this study. Thus, these results corroborate with [44] which showed that the lack of formal instruction for patients with drug-resistant epilepsy may be one of the factors that compromise therapeutic adherence.
Through studies of medication use, "Pharmaceutical Care", as a model of professional practice, becomes appropriate for evaluating and monitoring potentially modifiable factors of non-adherence (forgetfulness, AE, patient concerns) with the possibility of constructing criteria to enhance the quality of pharmaceutical services and to detect failures in pharmacological treatment [45].
Despite the limitation of the Brazilian guideline in the face of new adjuvant AEDs in the treatment of pharmacoresistant epilepsy, the list of antiepileptic drugs available for the first lines of treatment of this health problem is similar to the drugs set out in the main current guidelines such as, for example, the American [46], the Scottish [47] and the Belgian [48] guidelines.
Study limitations (bias)
Data collection was performed in a single hospital. Findings may also be understated because causality assessments were performed using interviews, chart review, and clinical judgment. This approach can make it difficult to identify possible confounding variables not described in the medical records and questionnaires, and the results can change according to the complexity of the hospital, the judges who carry out the causal association and the prospective or retrospective study design. However, the study has strengths that are important for the evolution of the state of the art, as this study generated a vast amount of information about the drug-resistant population, thus contributing to the evaluation of important points in relation to the management of pharmacological treatment.