The pharmacological treatment of epilepsy in adults

Abstract

The pharmacological treatment of epilepsy entails several critical decisions that need to be based on an individual careful risk–benefit analysis. These include when to initiate treatment and with which antiseizure medication (ASM). With more than 25 ASMs on the market, physicians have opportunities to tailor the treatment to individual patients´ needs. ASM selection is primarily based on the patient's type of epilepsy and spectrum of ASM efficacy, but several other factors must be considered. These include age, sex, comorbidities, and concomitant medications to mention the most important. Individual susceptibility to adverse drug effects, ease of use, costs, and personal preferences should also be taken into account. Once an ASM has been selected, the next step is to decide on an individual target maintenance dose and a titration scheme to reach this dose. When the clinical circumstances permit, a slow titration is generally preferred since it is associated with improved tolerability. The maintenance dose is adjusted based on the clinical response aiming at the lowest effective dose. Therapeutic drug monitoring can be of value in efforts to establish the optimal dose. If the first monotherapy fails to control seizures without significant adverse effects, the next step will be to gradually switch to an alternative monotherapy, or sometimes to add another ASM. If an add‐on is considered, combining ASMs with different modes of action is usually recommended. Misdiagnosis of epilepsy, non‐adherence and suboptimal dosing are frequent causes of treatment failure and should be excluded before a patient is regarded as drug‐resistant. Other treatment modalities, including epilepsy surgery, neuromodulation, and dietary therapies, should be considered for truly drug‐resistant patients. After some years of seizure freedom, the question of ASM withdrawal often arises. Although successful in many, withdrawal is also associated with risks and the decision needs to be based on careful risk–benefit analysis.

Adherence to Epilepsy’s Medical Recommendations

“…In our study, in patients with confirmed drug resistance, the risk of non-compliance with the recommendations when assessed according to the PRCS was almost five times lower (OR = 0.22, 95% CI: 0.05–0.99, p = 0.0493), while on the authors’ scale, the risk of non-compliance with medical recommendations was approximately three times lower than in patients without such resistance (OR = 0.34, 0.16–0.69, p = 0.0032). Although the level of compliance with medical recommendations among patients of the Outpatient Clinic was higher in patients with confirmed drug resistance than in patients with a good response to treatment, it should be considered if drug resistance, especially in those patients who did not follow the recommendations, did not result from the lack of compliance with medical recommendations [ 74 ].…”

Imperatorin interacts additively with novel antiseizure medications in the mouse maximal electroshock-induced seizure model: an isobolographic transformation

“…From a theoretical viewpoint, the additive interaction between two drugs may be clinically efficacious because of the low doses of both drugs administered to the patients offering the same anticonvulsant effects. If monotherapy with ASM is conducted in maximally tolerated doses of an ASM, some adverse effects may occur [ 33 – 35 ]. In such a situation, a duo-therapy with low doses of both ASMs may be helpful for epilepsy patients offering seizure suppression with concomitant reduction of adverse effects accompanied by the treatment with ASM in monotherapy [ 6 , 36 ].…”

Perampanel’s forgiveness factor in a variable medication adherence paradigm in a rat model of chronic epilepsy

“…While this may seem to differ from what one might expect in the patient, there are a few key differences that should be considered. Rather than initiating treatment soon after the onset of a reported seizure, which is standard clinical practice [ 31 ], we started PER therapy in animals with established epilepsy that may have been inherently more refractory. Moreover, unlike in clinical practice when the dose is often titrated to find adequate seizure control [ 31 ], we used a fixed-dose dosing paradigm, which certainly highlights an important limitation to be addressed in future investigations.…”

“…Rather than initiating treatment soon after the onset of a reported seizure, which is standard clinical practice [ 31 ], we started PER therapy in animals with established epilepsy that may have been inherently more refractory. Moreover, unlike in clinical practice when the dose is often titrated to find adequate seizure control [ 31 ], we used a fixed-dose dosing paradigm, which certainly highlights an important limitation to be addressed in future investigations. Nonetheless, many features of the post-KA rat emphasize strengths of this model to support further investigation into whether medication nonadherence may contribute to future pharmacoresistance with different ASM therapies, a limitation that was not addressed by the present investigation.…”