Mental disorders in epilepsy

tic seizures. However, as notes K. Wolf (1997), it is well known that in some cases even when the dose was increased to toxic, seizures are not cropped, and it is nesessary to decide whether to transfer to another drug or to add to an existing drug another one.

C. Wolf (1997) points out that at present, the studies showing synergism of several drugs are available, but none of the current researches do not confirm that monotherapy in the absence of a therapeutic effect is superior to polytherapy.

Contemporary concept of the first, second and third line of the selection of preparation with conducting of mono-therapy K. Wolf (1997) substantiates by the following positions.

With conducting of mono-therapy in the permissible therapeutic dosages by antiepileptic means the appearance of side effects is less probable, however, despite the fact that in poly-therapy the dose of each medicine is frequently lower than with the mono-therapy, medical interactions are sometimes unpredictable, and the concentrations of medicine in blood frequently exceed the required level.

With polytherapy the reduction in the concentration of precisely that drug, which has the maximum therapeutic effect is possible.

However, as the author notes, in 25-30% of cases it is noted the ineffectiveness of mono-therapy by the drugs of any line of selection. In such cases, the use of a combination of drugs is necessary and the underlining for polytherapy should be based on certain principles.

The advantage possess anticonvulsant combinations having different mechanisms of action.

The dose of the first of the assigned drugs must be adapted taking into the account possible medicinal interactions during the combination with the second drug (for example, valproate of sodium inhibits is the metabolism of many preparations, and this leads to the appearance of toxic reactions as a result of a notable increase in the concentration of the first medication).

There are not predicted interactions of the fermentation-indu- cing drugs (carbamazepine, phenytoin, phenobarbital) on their influence on the concentration in the blood to a considerable degree.

To apply simultaneously more than three drugs, according to K. Wolf (1997), is not reasonable.

At the same time, M.Ya. Vayntrub (1986) notes that to patients with the explicit signs of progressive course of epileptic process already in the initial stage is necessary to prescribe the combined drug treatment.

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This finds confirmation in last data of N. Adachi et al. (1997), according to which 209 patients with epilepsy with the monthly seizures prolongedly assume on the average 2-3 different antiepileptic means. More than 50% patients at the age 60 years and it is older, according to the data of G. Baker et al. (1997), simultaneously take phenytoin and carbamazepine. The same combination of drugs is used by A. Horvath (1997) during the treatment of patients with epilepsy “with the psychotic reactions”. Improvement in the mental condition in “those lowered and clumsy” of patients, primarily treated with one drug, H. Matthis (1997) notes after their two-year-old observation in “the regime of mixed (with lamotrigine) antiepileptic medication”.

As a further means of ongoing drug therapy with epilepsy R. Began et al. (1997) recommend lamotrigine, which, according to the authors, has a wide range of effectiveness. “A good response,” to application for several years of lamotrigine F.M. Besag et al. (1997) note during the addition of the drug to the treatment in patients frequent absences by valproate of sodium, by ethosuximide or by metsuximide.

Increase in recent years of the number of cases of the manifestations of intoxication in patients by antiepileptic means Sh. Bibileishvili (1997) connects with the wide introduction into the clinical practice of mono-therapy. After intensive detoxification and reduce the toxic dose of the drug in such patients the author applies bi-therapy in combinations of carbamazepine and phenobarbital, carbamazepine and phenytoin, phenobarbital, and phenytoin, appointed by him in the medium therapeutic doses, yielding a stable positive effect in about 2 years.

With mediotemporal epilepsy D. Cavalcanti et al. (1997) to that which was carried out for at least 3 months of drug therapy is attached vigabatrin, lamotrigine or gabapentin therapy and attain a decrease in the group of the patients of the medium frequency of seizures. According to A. Richens et al. (1997), tiagabine is effective additional therapeutic means with all types of partial seizures.

To patients with resistantial temporal epilepsy L. Kalinina (1997) successfully uses the combination of carbamazepine and lamotrigine. According to G. Regesta et al. (1997), any combination of two preparations suppresses seizures almost in third to that of the resistance cases. Approximately the same results give S. Viteri et al. (1997) with the description of “additional treatment” of vigabatrin 818 patients with epilepsy older than 14 years, when they

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report, that under the conditions of poly-therapy this drug “suppresses seizures in 32,2% of cases”.

According to our data, a fairly pronounced “combined”, i.e., simultaneously anticonvulsant and psychotropic effects were characterized by also such medications, as meprobamate, nitrazepam and phenazepam. Their application in combination with pyrazidol and benzobarbital during the treatment of our patients proved to be most favorable in the cases of predominance in the clinical picture of transitory and schubweise affective psychoses.

The results of the conducted by us investigation confirmed also noted in the literature (M. David et al., 1953; T. Negishi, 1965) possibility of effective action on the clinical picture of epilepsy of the small doses of aminazine and perphenazine. In many observed by us cases their combination with carbamazepine or convulex although did not exclude completely, for example, the appearance of paroxysms with the epileptic disease with the set aside exacerbation of process however rendered the expressed anti-psychotic effect in the form of reduction in the tension of passion and deactualization of delusional ideas.

Finally, we revealed the undoubted therapeutic effect of frenolon, neuleptil, moditen-depo, perphenazine in combination with phenobarbital, that was being expressed not only in the reduction of paroxysms, but also in reduction in the tension of passion, decrease in patients manifestations of negativism, decrease of the manifestation of stuporous and sub-stuporous disorders, preventive maintenance of the expressed psycho-motor excitation in the structure of twilight states during the treatment of patients with the unfavorable type of the course of epileptic process.

Thus, taking into account the fact that so far, lasting for decades antiepileptic treatment of patients with painstaking selection of appropriate medication for the patient in most cases continues to be carried out mainly by trial and error, and because of this, the main determinant of prognosis are biological factors that shape the stereotype of the disease, all the more evident becomes the need for further research of preventive therapeutic measures in relation to psychotic forms of epilepsy. Prospectively in this respect, apparently, is the establishment of correlation between the quality of care, the type of paroxysmal disorders and a form of psychosis in the earlier stages of the disease.

As the prerequisite for the development of strategy of antiepileptic therapy is important the establishment of the possibilities of con-

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ducting in each individual case of the “aiming” drug therapy with the data about the course and preferred localization of epileptic process. The preferable methods of the combined drug therapy, apparently, should be considered as the timely individually adequate mono-ther- apy, directed toward stopping the primary or prevailing epileptic focus, and also the thoroughly organized poly-therapy as a means of influencing the concerned functional whole system.

Based on the above data, it seems possible to conclude that the modern methods of medical treatment of advanced epilepsy are not yet sufficiently substantiated pathogenesis. It can be assumed that during multi combination drug therapy of mental disorders, with epilepsy, usually set a certain balance between the intensity of the pathological process destructive trends and the effectiveness of therapy, whereby there although aren’t undergoing radical changes in the course of the disease, but its clinical manifestations, undoubtedly are reduced.

In this regard, special attention should be paid to the so-called oligophrenic type of defect, which suggests an early progressive chronic epileptic process and, to our knowledge, is observed in frontal lobe epilepsy. According to Brodtkorb E. (1997), patients with mental retardation and epilepsy usually get a large number of drugs. It is in these patients, the author believes it is especially important to achieve a balance between control of epileptic paroxysms, and side effects of therapy. The negative impact of drugs on cognitive function may be masked by existing intellectual deficit.

Special position in the treatment of epilepsy in patients with the mental retardation, in the opinion of E. Brodtkorb (1997) and other authors, occupy some of new antiepileptic means – vigabatrin, lamotrigine, felbamate. Vigabatrin is the most effective in the treatment of infantile spasms, especially during their combination with the tuberose sclerosis and other damages of the brain (C. Chiron et al., 1991). Lamotrigine and felbamate are effective with symptomatic generalized epilepsies, including syndrome of Lennox-Gastaut (E. Schlumberger et al., 1992, and others).

The medicine of the first line of selection during the treatment of frontal and temporal epilepsies is arbamazepin and phenytoin (P. Shvartsmayr et al., 1997).

Ethosuximide, as valproat, is the medicine of the first line of choice with the typical absences. Stopping seizures during the treatment by ethosuximide is observed in 90% of patients. Metsuxi-

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mid has the same anti-convulsant profile as ethosuximide. However, it is more effective during the treatment of simple and complex partial paroxysms with some forms of myoclonic seizures. Having the frequent and expressed side effects, it is adapted as the preparation of the third stage of selection (K. Wolf, 1997).

Probably following the data, as pathogenic or adequate at the present time can be considered an antiepileptic combination therapy, which reaches such condition of the patient, in which, along with signs of clinical improvement there are absent expressed toxic effects and the patient socially becoming less dependent on their disease than before therapy. In light of this position should be, apparently, as urgent examined the principles of the antiepileptic therapy, developed by domestic researchers in the recent decades (E.S. Remezova, 1965; A.I. Boldyrev, 1971; S.A. Gromov, 1977; V.A. Karlov, 1990, and others): the principle of etiopathogenetic approach to the treatment of epilepsy, the principle of the clinico-pharmacological validity of treatment, the principle of the individualization of treatment, including the selection of the optimum doses of alternative preparations and their interchangeability, the principle of continuity and optimum duration of antiepileptic treatment.

If the first two principles were somehow already discussed above, the validity of the rest, has to be illustrated specifically .

To the special role of the individualization of treatment in the achievement of the reliability of antiepileptic therapy at the childhood indicates the data, obtained by W.F. Arts et al. (1997). G. Avanzini (1997) reports that the intracellular record in various human tissues or tissues of animals attests to the fact that the individual elements of epileptic neuronal aggregates present the recurrent paroxysmal changes in the polarization, synchronous with the spikes on EEG. In another of his work G. Avanzini (1997) cites experimental data, which, in his opinion, confirms the hypothesis about the fact that the stability to the preparations is the result of structural epileptogenic deviations in the brain. In particular, according to the data of the author, the comparative study of the experimentally caused disorders of neuronal migration can present the proofs of the presence of deviations in the interrelations between the individual cellular elements. This is equally inherent in synaptic cellular activity, which, as it follows from the nature of the action of antiepileptic means, proves to be deeply changed.

In this connection is interesting the allocation of A. Maksutova and V. Fresher (1998), the so-called psychopathological syndrome-

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targets during the treatment of epilepsy (Table. 3). As for the mode of regularity medical treatment of epilepsy, among the most frequent causes of “poor compliance,” of the latest J. Beaussart-Defaye et al. (1997) note the rejection of drug treatment, irregular and unauthorized use of medication discontinuation of medication.

The number of the contemporary authors examine questions of the duration of the antiepileptic drug therapy, sufficient for achievement of optimum therapeutic effect.

G. Braathen et al. (1997) suggest that an individual’s prognosis may be determined depending on whether the treatment can be withdrawn one year after the start or it has to be continued. D. Marinkovic et al. (1997) find that satisfactory control of seizures using lamotrigine achieved during treatment with this drug for at least 6-12 months. V. Roman et al. (1997) examined the 5 patients with no seizures within 3-7 years, but with deviations in the EEG. In all cases where they have been used lamotrigine, EEG significantly normalized and seizures were observed. After one year of treatment with vigabrinom all the patients of P. Veggiotti et al. (1997) found reduction of seizures of more than 50%, and some of them – slowing psychotic symptoms.

According to our data, the reduction of the clinical manifestations of disease only to a certain degree can contribute to resolution of questions of the social-working rehabilitation of patients, that does not in turn exclude, however, the need of developing the more adequate approaches to the search for the pathogenetically substantiated therapy.

In light of the aforesaid for refining the symptoms (syndromes)- targets in the process of treating the mental disorders with epilepsy we consider it necessary to compare our findings with the data of M. Sh. Wolf (1991).

Our observations in their clinical content coincide with the observations of this author, who indicates that besides those established in the course of the clinico-electroencephalographic inspection of the patients versions of localization of epileptic process there are clinical signs “of mutual transformations”, “stratifications”, “mixed forms”, the manifested in the complex structure paroxysms, nonpsychotic, psychotic and intellectual disorders in the patients with epilepsy.

To us it is possible in this connection to build the following scheme.

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Table 3

Psychopathological “syndrome-targets” and the selection of preparations

(A. Maksutova, V. Fresher, 1998)

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With the localization of epileptic centers “in the diencephalic region” M.Sh. Wolf used “weak sedative, moderately antilogarithmic and strong antihistaminic property” of diprazin. For the purpose of “braking influence on the amygdala-like nuclei of limbic system” was applied chlordiazepoxide – “polysynaptic interneuronal blocker, which possesses sedative properties”. With the presence of the center of irritation in the mediobasal structures of the brain – diazepam with its “anti-alarming and anti-phobic action”. With “polar fluctuations of mood” in patients the author used thioridazine, either tazepam or meprobamate, but for purposes “of improvement in the mood” in the depressive disorders – amitriptyline, which possesses also the “expressed antiparoxysmal action”, and also valproates, “rendering not only antiparoxysmal, but also thymo-normalizing influence”. In this connection it should be noted that the contemporary authors connect the development of depressive disorders with epilepsy with the limbic system (A. Kanner, J. Nieto, 1999).

In the cases of temporal lobe of epilepsy to “the correctors of behavior” in patients with “expressed psycho-motor disorders” the author carried pericyazine, to lorazepam and ospolot, just as carbamazepine. suppressing temporal psycho-motor seizures. For treating the psycho-motor and psycho-sensory paroxysms was recommended amitriptyline and methinedione, while for treating of paranoid, hal- lucinatory-paranoid syndromes, syndrome of Kandinsky – aminazine and “different psychotropic means with the more powerful anti-psy- chotic action”. However, for treating the patients “with the obtrusive ideas” – seduxen, azaphen and amitriptyline.

In the cases of frontal lobe epilepsy for treating “twilight states, dysphorias, and also epileptic psychoses, which were being accompanied in the patients with affective tension, irascibility, psycho-motor excitation and explosiveness”, M.Sh. Wolf used aminazine and levomepromazine “as the medicine of emergency”. As the drug, at the large doses which suppresses the generalized convulsive seizures, especially during their series and status treatment – seduxen. For treating the generalized convulsive seizures – clonazepam in its combination with barbiturates or diphenine or, in the cases of their special resistance to the therapy -valproates. During the expressed manifestations of oligodinamia and bradyphrenia the author used acephen as “corticosubcortical neuro-anabolic with the stimulating action”. In the complex with other antiepileptic means – pantogam and in the combination with diphenine, carbamezepin or seduxen – amitriptyline.

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For patients with frontal lobe epilepsy with the monotonic behavior, not connected with the real situation, which is interrupted by motor excitation, M.Sh. Wolf recommended neuroleptics (neuleptil in combination with the aminazine) or valproates.

The special interest for our study present the observations of the author, whose content, in our opinion, can be interpreted as the proof of existence of the reciprocal effect of the functional systems of brain, to different degree interested in the course of the development of epileptic process. The possibility of such interaction requires polytherapy – mainly in the form of combination therapy with classical antiepileptics, anxiolytics and antipsychotics.

By M. Sh. Wolf it was, in particular, noted the high efficiency of seduxen during the treatment of psycho-motor seizures and pseudoabsence, beginning of which preceded different vaso-vegetative phenomena, and phenazepam – “as the means of pressing aid for stopping sharply appearing dysphorias”, during application of which after 1-2 days in patients is reduced the affective tension, anxiety and fear decrease or disappear, sleep is normalized, vaso-vegetative paroxysms are reduced and disappear. These examples, in our opinion, can indicate interaction of mediobasal of temporal, in general temporal and frontal formations.

About the same kind of relationship of cerebral structures one can think , tracing conducted by the author comprehensive analysis of the actions of the “mood stabilizer” carbamazepine, to use them for the “prevention of affective psychosis” and relieve “secondarily generalized seizures with focal” temporal “and especially the beginning of the attacks” temporal “epilepsy that occur “in the form of psychomotor paroxysms, oral and swallowing automatisms and twilight feeling.” It is remarkable in this connection also the fact that the complex application of carbamazepine with other antiepileptic traditional means, the author considered as “especially shown patients with epilepsy with the polymorphous seizures”.

“Painful feeling of fear, which is combined with the general affective stress with the temporal localization of process”, “circular disorders of mood”, “disinhibition of emotions and passions with the preferred defeat of frontal region”, require, in the opinion the author, the combined application of anticonvulsive means, tranquilizers and antidepressants.

One should emphasize that presented by us on the basis of literature and own experiment data the recommendations are only the

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overall scheme, which one should adhere to during the organization of the combined drug therapy of patients by epilepsy, which takes place with the mental disorders. A strict individualization of their treatment is necessary to understand as the observance of the old principles of doctoring, which are consisted in the fact that is treated not the disease, but patient, that the treatment is greater skill, than science, and that without the creation of the atmosphere of the partnership between the doctor and the patient adequate treatment is impossible.

In this sense should be, for example, recognized as valid the observation of V.V. Kalinin (2011) about the fact that standard and united criteria on the selection of antidepressants with epilepsy doesn’t exist, with exception of the fact that the selective preparation must not decrease the threshold of convulsive readiness.

From this point of view also of interest are several observations relative to interaction of antiepileptic and anti-psychotic preparations, given in the survey of R. Guarnieri et al. (2004). According to the data of S. Koch-Stoecker (2002), epileptogenic threshold is lowered by all anti-psychotic drugs and pharmacokinetic interactions between the antiepileptic and anti-psychotic preparations can change the assumed therapeutic influences, that explain the need for application of the lowest possible doses of those or others. At the same time the author notes that with the use of phenothiazines occurs the smallest risk of the appearance of extrapyramidal disorders. M.R. Trimble (1995) notes that in this sense haloperidol is the safest medicine. Out of the atypical neuroleptics for treating the epileptic psychoses D. Blumer et al. (2000) prefer risperidone. R. Guarnieri et al. (2004) with the use of the combined therapy by antiepileptic and anti-psychotic drugs assume expedient to avoid abrupt changes in the dosages of these and others.

Regarding the use of psychotherapy in treatment of patients with epilepsy, in the domestic practice to date is mainly used so-called rational therapy. It is necessary to note that in recent years the attention to WHO is paid not only to psychotherapy, but also to so-called traditional or folk medicine. In this case it is indicated that psychotherapy occupies in folk medicine one of the key places. However, one should recognize that in ten of world medical associations, whose activity is one way or another is approved by WHO and has a relation to the treatment and rehabilitations of the persons with the mental disorders, today is not found the places of analogous level for the

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