Mental disorders in epilepsy

Topiramate. – Weakness, fatigue, psychoses, depression, the tangled nature of consciousness, disturbance of the concentration of attention, retarding associative processes, amnesia, emotional lability, fears, irritability.

Levetiracetam. – Sleepiness, vertigo, anorexia, ataxia, asthenic syndrome, tremor, amnesia, aggression, agitation, depression, anxiety, psychoses.

Zonisamide. – Sleepiness, ataxia, anorexia, agitation, irritability, depression, psychoses.

Lacosamide. – Sleepiness, tremor, the decreased coordination, depression, fatigue.

Rufinamide. – Sleepiness, insomnia, anorexia, anxiety. Stiripentol. – Loss of appetite, retardation, a cognitive decrease,

ataxia, aggression, anorexia, the disorder of sleep, excitability, hyperkinesis, irritability.

We adhere to the view, according to which the concept of alternative psychosis should be used only in the explicit cases “of the replacement” of seizure by the psychosis as a result of therapeutic action, but not in a broader sense. According to our research, the assessment of the dynamics and characteristics of alternation in epilepsy syndromes, including those with many years of of its medical treatment, it must be assumed that, following the personality changes in the socalled epileptic type, which is the earliest differential diagnostic sign in patients, a period of active development of paroxysmal syndrome, and the latter gives way to their period of dominance in the clinical picture of the disease psychotic disorders, which often, in turn, give way to the stages of the formation of epileptic dementia.

What is the impact of antiepileptic therapy on a regular formation of such a stereotype of epilepsy – the answer to this question can probably be obtained in the course of special studies.

The purpose of present chapter is the study of the possibilities of the combined treatment of epilepsy with the use of an antiparoxysmal therapy, psycho-pharmacotherapy, psychotherapy and sociotherapy.

Combination of anticonvulsive (M. David et al., 1953) and antipsychotic (J. Delay et al., 1953) effects of aminazine from the very beginning of its application attracted attention of many researchers. With the sharp epileptic psychoses J. Delay et al. (1953) recommended the application of medicine simultaneously with the physical cooling. Effective was the application of aminazine in epileptic de-

231

lirium, catatonic excitation and other various forms of sharp epileptic psychosis (T.A. Nevzorova, 1960; E.S. Remezova, 1965, and others). It was recommended the use of aminazine for the involution of the action of barbiturates for purposes of smoothing and warning of explosiveness in patients (N.P. Statsenko, 1961; V.S. Pozdniakov, 1963, and others).

During the treatment of patients it was proposed to combine aminazine with the antidepressants and the tranquilizers (V.P. Belyayev, 1964; L.P. Lobova and T.A. Dobrokhotova, 1964; V.S. Pozdniakov, 1967 and others). The action of anti-convulsants was contradicted to the effectiveness of chlorpromazine and perphenazine during the treatment of hallucinatory-paranoid states and catatonic manifestations (T. Negishi, 1965; V.S. Pozdniakov, 1967). As effective during the treatment of epileptic psychoses was recognized the combination of carbamazepine with the aminazine, levomepromazine or haloperidol (T.A. Nevzorova, 1960, and others).

If, however, we consider that in Russia for many decades, the vast number of epileptic patients under the supervision of the district psychiatrist, take an active treatment of so-called anticonvulsants and the original meaning of the concept of alternative psychosis largely retains its value, the only adequate methodological approach to the verification legitimacy of the existence of this concept should be recognized clinical research.

A number of works of the period of 1970-1980’s was typical of generalize long-standing practice of active treatment of epileptic psychosis, to find new methods to the treatment of the therapeutically resistant cases. For overcoming the varied inosculating between themselves reversible and irreversible syndromes as the substantiated therapeutic approach to the solution of problem was proposed the combined treatment (L. Diehl and H. Helmchen, 1973). As prognostically unfavorable at the plan of therapeutic prognosis were evaluated the cases of the combination of the large polymorphism of seizures with the transitory and especially with the protracted psychotic states (E.S. Remezova, 1974; V.P. Hermann et al., 1982). As appropriate preventive measures was used mutual potentiation and long-term application of anticonvulsant and psychotropic drugs in small and medium doses (R.G. Golodets, 1971; O.Z. Golubkov and R.G. Gismatulina, 1971; A. Stoudemire et al., 1983).

For example, in connection with reduction in the effectiveness of carbamazepine after 1,5-2 years of its continuous application one

232

should have for treating the depressive-hypochondriacal states combine this preparation with the mixture of Sereyskyj, the phenobarbital, the primidone, the chlorakonum, bromine, seduxen, tazepam, elenium, levomepromazine (R.E. Halperin et al., 1971; M.V. Levin et al., 1971), amitriptyline (N.N. Andreev, 1972), or to assign it as the additional means to the basic anticonvulsive treatment (V.F. Leksikova, 1971; V. Below, 1973; L.Y. Visnevskaya 1976).

Given the possibility of the development of psychosis during the end of paroxisms, was considered, along with anticonvulsants, a longterm application of psychotropic drugs (H. Helmchen, 1973; Z.D. Gavrilyuk, 1981; D. Blumer, 1982, and others). In particular – tryptizol and leptril (R.G. Golodets, 1971; Yu.I. Afanasjev et al., 1972), neyleptil (V.K. Kaubish et al., 1971), mesoridazine (Yu.I. Afanasjev, 1975), nitrazepam (M.S. Wolf et al., 1973; J. Huszar et al., 1973), chlormethiafole (H. Gebelt, 1973), sultiam (J. Huszar et al., 1973, and others), melperon (S. Kosanic, 1979).

With the protracted epileptic psychoses was indicated the possibility of the achievement of different quality of therapeutic remissions under the massive neuroleptic influence (A.R. Merdeev et al., 1972, and others), the combination of sulfozin and insulin-shock therapy (N.O. Narbutovich, 1972), the removal of the structures of the almond-shaped and partially hippocampal set of temporal lobe (B.M. Rachkov and V.A. Fedorenkova, 1978; N.M. Panchenko et al., 1982).

By R.A. Kharitonov et al. (1976) and O.Z. Golubkov et al. (1981) developed the schemes of the treatment of epileptic psychoses in the cases of the resistance of the latter to the drug therapy. With the ineffectiveness of antiepileptic and anti-psychotic means was assigned, in particular, the treatment by cholinolytic coma. Noting the need for a lower than during the treatment of so-called endogenous psychoses dosages of antidepressants and antipsychotics, N. Penin (1978), in each case of epileptic psychosis admitted advisable to seek cessation of seizures, since any therapeutic resistance, in his opinion, is a condition for of the development of psychosis.

In this regard, it is interesting to refer to the discussions of recent years on the desirability of a combination, during the treatment of epilepsy, of anticonvulsants, psychotropic of dehydration and other drugs to overcome its resistance.

As for the combinations of anticonvulsants, then by the most acceptable of them are recognized the combination of carbamazepine and sodium valproate, carbamazepine and vigabatrin, lamotrigine

233

and vigabatrin (I. Stolarek et al., 1993 E. Rerucca, 1995, EV Sorokova, 2004; W . Loescher, 2011; J. French, 2011). By “resistance” refers the lack of effect with sequential monotherapy of every possible anticonvulsants (using all the so-called bursts of choice), and all their possible combinations (M. Nikanorova, 1997).

Valproates as the cure of overcoming resistance epilepsy are more rapid than other anti-convulsants (phenytoin, phenobarbital, primidone), penetrate through the blood-brain barrier. They render not only anticonvulsive action, but improve the mental condition of patients (P.A. Temin et al., 1997).

Special position in the treatment of resistant epilepsy, according to E. Brodtkorb (1997) and K. Wolf (1997), occupy some of the new anti-convulsants – vigabatrin, lamotrigine, gabapentin, felbamate. E. Maxoutowa (1997) considers that besides the normothymic effect, lamotrigine on the anticonvulsive effects can be compared with carbamazepine and valproate of sodium. F. Monaco (1997) focuses attention on two aspects of the action of vigabatrin: it can cause the development of psychosis, but during the adequate application the very same it can be used, also, for eliminating the depression.

Brodtkorb E. (1997) suggests that patients with intellectual disabilities or organic brain damage often require combination therapy with anticonvulsants and antipsychotics; however, the high doses of neuroleptics can provoke seizures, explaining this partly by their sedative properties. By most “epileptogenic” neuroleptics (J.A. Cold et al., 1990) are counted chlorpromazine and clozapine, while piperazine phenothiazines (perphenazine) influence the threshold of convulsive readiness moderately, and butyrophenones and thioridazine

– are insignificant. In this connection is interesting the recent statement of P. Shiozawa et al. (2011) about the successful treatment of the cases “refractory schizophrenia” by the combination of lamotrigine and clozapine.

Carbamazepine in the chemical structure is close to the tricyclic antidepressants and is the medicine of the first line of selection during the treatment of partial epileptic paroxysms, including seizures with the secondary generalization (K. Wolf, 1997).

Should be noted that the problem of drug-resistant forms of epilepsy recently received special attention. In the general population of adult patients with epilepsy who regularly attend clinic, J. Beaussart-Defaye et al. (1997) considered 37% of patients resistant to the drug therapy. According to D. Besana et al. (1997), the total

234

number of children with epilepsy, directed to the hospital, with intractable epilepsy were detected in 12%. According to M.S. Picot et al. (1997), the incidence of refractory epilepsy in the population is 0.1%.

In the complex of the combined treatment in such cases are included the antidepressants, behavioral of technology, surgical treatment (F.M.S. Besag et al., 1997), alternative therapy (T. Betts, 1997; S. Uhlmann et al., 1997). From other side, H. Mayer et al. (1997) note that the antiepileptic treatment can be the factor, which facilitates the optimization of cognitive therapy.

Complex application of vaso-active drugs and neuroprotectors L. Mouzitchouk et al. (1997) consider as one of the factors, which facilitate overcoming resistance epilepsy.

In this chapter, we present the results of our analysis of longterm (13.3 + / -0.6 years) monitoring of the treatment efficacy of 450 patients (234 men, 216 women) with epilepsy, flowing with mental disorders.

As the main position was accepted that the development of clinical criteria of social and labor prognosis of remote stages of the epileptic process flow can not do without evaluating the effectiveness of the use of modern combination (antiepileptic and psychotropic drugs ) medication, used to prevent the onset or worsening of patients disability. Many authors recognize that the organization of medical care for patients with epilepsy, the purpose of which is to prevent the worsening of the patients, depends on the level of organization of health services in the country (S.M. Al Deeb, 1997; L. Andermann, 1997; A. Bener et al., 1997; N.E. Bharucha et al., 1997; S. Cerino et al., 1997, and others). In this case even in the satisfactory countries, according to the data of the study, carried out by W.F. Arts et al. (1997), in 45% of cases of development of epilepsy in children prognosis is evaluated as “poor”. The influence of the treatment of epilepsy on the quality of life of elderly people is evaluated more optimistically – unfavorable prognosis is noted in them in 30% of cases (G. Baker et al., 1997). J. Beaussart-Defaye et al. (1997) separate number of the factors, which facilitate the loading of therapeutic prognosis with epilepsy: the failure of patient of the timely medicinal therapy, the use of traditional medicine, the irregularity of medication used and other.

In the opinion of K. Wolf (1997), the optimum duration of the treatment of epilepsy before the cancellation of anti-convulsants therapy is 2-3 years. The refinement of the factors of the risk of the

235

renewal of paroxysms after cancellation of anti-convulsants therapy is always paramount prognostic task. The most significant factors of risk are represented in Table 2.

According to R. Nikolaishvili (1997), after discontinuation of medication in 2-3 years after the cessation of seizures frequency of relapses in patients ranges from 15 to 70%.

Table 2

Factors of the risk of the renewal of seizures after cancellation anti-convulsants therapy (K. Wolf, 1997)

The effectiveness of drug therapy was evaluated by us according to the possibility of its influence on the basic trend of development of disease – type of the course of epileptic process.

Corresponding statistical analysis (with the application of associative coefficient of G. Yule) showed that the prolonged application of average doses of classical antiepileptic means (phenobarbital, primidone, dipheninum, carbamazepine), and also average and high doses of neuroleptics (aminazine, levomepromazine, haloperidol, trifluoperazine, moditen depo) is more effective with the favorable course of epileptic process. In the cases of the course of disease with the set aside exacerbation of process and especially with its unfavo-

236

rable course drug therapy rarely leads to the curtailment of seizures and the complete disappearance of psychotic disorders.

Upon consideration of all basic principles of conducting antiepileptic therapy, proposed by E.S. Remezova (1965): complexity, individualization, the timeliness, adequacy and opportuneness of the application of doses of medicines, continuity, duration and orientation of treatment to a change in the clinical picture of disease, – our evaluation of the results of therapy were reduced to the following.

Overall, two out of every three cases studied by us could talk about the low efficiency of the therapy on a regular basis. With regard to the inadequacy of the use of certain drugs, the late start of treatment and the treatment of irregularities, then, according to our data, these factors are evenly distributed on the types and stages of the disease. At the same time the level of effectiveness of drug therapy varied as in the cases of exacerbation of the disease, and in cases of treatment failure of patients, and among the reasons for the low efficiency of regular drug therapy in general in the first place was its late start.

It should be noted that in the contemporary literature actively develops a question about the criteria of effectiveness of the methods of the therapy of epileptic disease. The majority of the authors proceeds from the fact that the anticonvulsive therapy, especially in the persons with the mental disorders, must not be rigidly oriented for reaching of the complete control of seizures, because the side effects of treatment often cause more damage than the seizures themselves (E. Brodtkorb, 1997).

The optimum method of treatment is anticonvulsive therapy with the smallest possible dose of preparation (E.N. Reynolds et al., 1981). Among four most widely used anti-convulsants carbamazepine and valproate of sodium, in the comparison with phenytoin and phenobarbital, to a lesser degree adversely affect the cognitive functions (M.R. Trimble, 1987). It is, at the same time, necessary to remember that the presence and degree of the manifestation of the defeat of the brain aggravates the negative influence of anti-convulsant on the cognitive functions (C. Helmstaedter et al., 1993; R.J. Thompson, 1993).

“Necessary”, according to the recommendations of WHO (World Health Organization) (1990), are the preparations, which satisfy the requirements of an improvement in the health in the majority of patients. They include сarbamazepin, valproate of sodium, phenytoin, phenobarbital, вiazepam and ethosuximide. As noted by K. Wolf

237

(1997), less clearly are emphasixed “anticonvulsants of the first line of choice.” In the Anglo-American literature these include the first four listed above, in German – the first two.

Positive, in our opinion, is the fact that in recent years more attention with the estimation of the effectiveness of the conducted antiepileptic therapy researchers turn for the observance of the clinical uniformity of the groups of the studied patients.

G. Baker et al. (1997), for example, with the use of the developed by them questionnaire studied the effectiveness of the influence of lamotrigine on the gravity of paroxysms, mood, behavior and general quality of life in 33 children and adolescents with epilepsy and incapacity to the instruction. The effectiveness of treatment by preparation was expressed in the fact that together with the reduction of gravity of the manifestations of paroxysms in patients occurred a substantial improvement in the behavior, capability for communication and realization of medium.

For establishing the effectiveness of antiepileptic means G.A. Baker et al. (1997) propose the creation of the matched protocol of a study of the results of treating the patients through the estimation of their cognitive functioning.

Efficient and effective scale of the estimation of cognitive abilities in patients, in spite of the negative influence on them of the toxic antiepileptic preparations, in the opinion of G.K. Banks et al. (1997), contributes to the development of the clinical tests of medications. The difficulty of designing of such tool of estimation indicates B. Bourgeois (1997), assuming that the estimation of cognitive functions and behavior of the patients with epilepsy in the process of their drug treatment varies in the limits from the ignoring to the overestimation depending on the predominance until today of one or other point or another of view. Difficulties in the measurement of the success of treatment notes also B. Brulde (1997), explaining by their uncertainty of aim in the permission of a question, that to consider the criterion of the success: clinical improvement or an improvement in the quality of life. His doubts about the necessary sensitivity of measurements in different groups of patients in terms of evaluating therapeutic effects of changes also expresses D. Chadwick (1997).

As the well-known confirmation of the lawfulness of a similar kind of doubts it is possible to give also data of D. Cavalcanti et al. (1997) about the fact that a homogeneous population of patients with temporal lobe epilepsy, medial, which they treated with various new

238

antiepileptic drugs (vigabatrin, lamotrigine and gabapentin), regardless of the medication, the maximum positive clinical effect of the treatment was observed by them in first 3 months of treatment and was equally reduced significantly during the year.

With the analogous results of treating the resistance forms of epilepsy in children with phenobarbital, primidone, clonazepam and ethosuximid with the periodic additions of celontin , bromides and ospolot Е. Коrn-Merker et al. (1997) come to the conclusion that the precise analysis and diagnosis, consecutively complete utilization of therapeutic doses and sufficient presence of antiepileptic means for guaranteeing the limit of compatability help to transfer epilepsy into curable state.

In the opinion of B. Spilker (1997), quality of life is the final point of the estimation of the effectiveness of therapy (i.e. by its purpose). The measurement of the corresponding parameters in the more thinned form is, possibly, the matter of future, and their study will, possibly, play more efficient role in the clinical practice, than this can be noted today.

We separately studied the question of the value held by the precinct psychiatric therapy for the individual prognosis depending on the flow of the main forms of epileptic psychosis. It was, in particular, established that in the cases of transitory psychoses the more expressed therapeutic effect occurs at the stages of disease before the appearance in the patients signs of dementia. At the schubweise and chronic psychoses steady therapeutic remissions are reached in the periods of the stabilization of epileptic process at considerably later stages.

Taking into account stated, it seems necessary to develop a classification of epileptic psychosis, which, along with the identification of target syndromes would ensure compliance with the principle of dynamic therapy (GY Avrutsky, AA Neduva, 1988).

Conducted by us for this purpose type mapping process of flow epileptic in patients with predominant type of EEG revealed a correlation between the predominant localization of epileptic process and register productive psychopathological disorders: affective, delusional and catatonic.

As was already mentioned in previous chapters, the predominance in the studied patients of affective and affective-delusional disorders was more characteristic for the favorable course of disease, with which among the paroxysmal disturbances, key place occupy

239

vegetative paroxysms. Hidden, without the signs of lateralization, epileptic activity, which is revealed on EEG with the photo stimulation or hyperventilation, testifies the “centrencephalic” or “deep” localization of epileptic process. Epilepsies with the set aside exacerbation of process are more characteristic, according to our data, the hallucinatory-delusional forms of psychosis and the polymorphism of paroxysmal manifestations. In this case is typical resistance to the therapy of temporal seizures (psycho-motor and psycho-sensory), predominantly parietal-temporal and temporal localization of the center of epileptic activity, so-called temporal epilepsy.

Finally, in the cases of the unfavorable course of disease, we have established correlations between the polymorphism of psychotic manifestations, the presence in structure of the psychosis of catatonic disorders, the predominance in the general structure of the paroxysms of generalized convulsive seizures and dysphorias with the temporal-frontal localization of epileptic center, so-called frontal lobe epilepsy.

These clinical and electrophysiological data allowed us to consider appropriate combination of differentiated (by ES Remezova, 1965) antiepileptic therapy with directional integrated use of tranquilizers, antidepressants and antipsychotics. As to the required components of poly-therapy we gave preference to the means, which possess not only “preventive”, but also simultaneously “direct” effective action both on the different kind paroxysms and to the wide spectrum of the psychotic disorders of affective and affective-delusional register. To such means were first of all related carbamazepine and valproates.

The adequacy of the use of mono-, bi-and polytherapy of epilepsy in recent years received much attention due to the introduction of new antiepileptic drugs.

The appearance of the antis-convulsant, the spectrum of action of which includes the anti-psychotic, anti-obsessive, thymoleptic, normothymic effects, including of carbamazepine, valproates, lamotrigine and others, considerably enlarges the possibilities of treating the patients (A. Maksutova et al., 1998).

In the valid opinion of K. Wolf (1997) and E. Perucca (1997), the discussion about strategy of anti-convulsant therapy for a period of many years has a number purely scholastic characteristics. The authors practically do not have doubts about the fact that in the majority of the cases the treatment must begin from one drug. A similar tactics in the majority of patients provides complete control of epilep-

240