**3. Cognitive side effects of antiepileptic drugs**

At the onset of epilepsy and prior to treatment cognitive impairment can be already observed in a large number of patients. Frequently detectable deficits can be found early in the course of the disease in attention, memory and executive functions [5].

Basically, all anticonvulsants can have a negative impact on cognitive performance. If any cognitive deficits before treatment existed, these deficits may be exacerbated. The most common negative effect of anticonvulsants is a decrease in information processing speed, reaction speed and concentration. Most treatment related cognitive disorders are reversible and fade after dose reduction or completely disappear after a change in substance. Only visual field defects with vigabatrine are irreversible, which is why this substance has been used only in individual cases and under strict ophthalmological control.

Among the anticonvulsants of the older generation valproic acid, carbamazepine and phenytoin have the most favorable cognitive side effect profile with

#### *Cognitive and Psychological Side Effects of Antiepileptic Drugs DOI: http://dx.doi.org/10.5772/intechopen.94308*

comparatively little effects on concentration, memory, information processing speed or word fluency. The newer generation of anticonvulsants with a rather minor influence on cognitive performance are lamotrigine, levetiracetam, gabapentin, perampanel, lacosamide, oxcarbazepine, eslicarbazepine and pregabalin [6, 7]. For lamotrigine and lacosamide - in individual cases also for oxcarbazepine and perampanel - improvements in cognitive partial performance (e.g. information processing speed, concentration, vigilance) have been described [8–11]. In Contrast, topiramate and zonisamide are anticonvulsants with a relatively unfavorable cognitive disturbance profile. However, bromine, phenobarbital and primidone can also be associated with cognitive disturbances (e.g. cognitive slowing), whereby these substances are rarely used in everyday clinical practice. In combination therapies, a frequently condition in refractory epilepsy, undesirable interference effects can accumulate.

Topiramate relatively often and sometimes very impressively leads to deterioration in language skills such as verbal fluency and word finding, to a slowdown in the speed of reaction and to decline in working memory. In general, these interference effects occur even at relatively low doses and also if the dosage is very slow. In addition, there does not seem to be a habituation effect, so that the disturbance effects persist even with long-term therapy. Patients with intelligence impairment react to topiramate with the same cognitive disturbances as intellectually unaffected patients: Slow reactions, reduced language skills and reduced working memory can be found [12]. Even if these patients already have cognitive impairments, an additional drug-related deterioration should not be neglected, as this can have a fundamental impact on everyday competence and independence.

The following case study is intended to illustrate the possible scope of these cognitive effects caused by topiramate: A 20-year-old man introduced himself to the epilepsy centre. He developed epilepsy when he was 14 years old. At that time he attended the 8th grade of a secondary modern school (in German: Realschule). His former neuropediatric put him on topiramate, which he had tolerated subjectively well to this day (a current daily dose at admission 400 mg). He did not remember negative cognitive effects during school and did not complain about it when he was admitted. Soon after onset of epilepsy, the patient switched from secondary modern school to secondary school (in German: Hauptschule –a school with a lower level of graduation). In the end, he left school without graduating and subsequently found no apprenticeship training position, so at the time of admission to the epilepsy centre, he has been working in a supermarket as a temporary helper. While treatment optimization he was given an alternative anticonvulsant. Before changing his mediaction, he underwent neuropsycholgical examination (**Figure 1**).

With a dosage of 400 mg topiramate, the patient displayed significant performance deficits in speech fluency, working memory and reaction speed were striking. These cognitive functions are associated with a successful performance in school: Linguistic skills are required to express yourself concretely and correctly in class and exams, to understand learning content and tasks and to apply or implement them. Working memory functions include the short-term holding and simultaneous manipulation of information – fundamental achievements to understand spoken language. If these skills are impaired or even slowed down, a student will not be able to adequately follow the lessons, which can lead to an overall failure in school. Though epilepsy can be accompanied with cognitive impairments or even global impairments of intelligence regardless of the medication, it is likely that a slight intellectual disability has caused the failed educational/professional career of our patient. After several months he came back to the epilepsy centre for further medication changes. At this point topiramate was completely discontinued.

The patient did not report any cognitive changes. However, he has started to catch up on the secondary school graduation. He even planned the next higher school graduation as well, to start apprenticeship as a car mechanic. We examined our patient again (**Figure 2**).

In contrast to the first neuropsychological examination, cognitive performances that have previously been below range (verbal fluency, reaction speed and working memory), were now within normal range. So, there were significant improvements in cognitive performance after stopping topiramate, which suggests that the deficits

#### **Figure 1.**

*Note: Percentile rank 16 = lower average limit compared to a healthy control group; reaction time = tasks on reaction speed, comprehension = task to understand language, TPM = topiramate; with 400 mg TPM, the patient's performance in almost all of the cognitive areas examined is below average compared to a healthy control group.*

#### **Figure 2.**

*Note: Percentile rank 16 = lower average limit compared to a healthy control group; reaction time = tasks on reaction speed, comprehension = task to understand language, TPM = topiramate; after discontinuing TPM (0 mg), all examined cognitive areas showed normal findings and thus shows a clear improvement compared to the previous examination (400 mg TPM).*

found earlier (and thus probably also the failure in school) are related to the drug topiramate. Based on this case study, the possibly life-long social consequences due to the decision in favor of a certain drug at a certain point in patient patient's life, is very impressive.

Zonisamide - similar to topiramate - can lead to cognitive disturbances with memory disorders, cognitive slowdown and word finding disorders [13]. In contrast to topiramate, a dose effect can be observed here (the higher the dose, the more serious the impairment). It is supposed that the negative interference effects fade, but this is not reported in all studies [14], so that under certain circumstances a therapy attempt could be considered despite the initial interference effects (e.g. if other anticonvulsants have not led to the desired therapeutic success despite increasing them to the limit of interference).

Benzodiazepines (clobazam, clonazepam, diazepam, lorazepam) are a group of anticonvulsant drugs with well-known and sometimes clear cognitive side effects (sedation, fatigue, concentration disorders). Apart from this, additional problems such as development of tolerance and the risk of addiction rule out these drugs for long-term therapy in epilepsy treatment. Apart from individual cases, they are used only as a bridge drug in medication changes and as an emergency medicine with one-time dose.
