Терапевтическое значение концентрации клозапина в плазме крови больных приступообразной шизофренией в состоянии симптоматической ремиссии

Schizophrenia is a chronic disease, where remission is defined not only by complete absence of symptoms but rather by the minimum degree of their intensity and by moderate patient’s maladjustment. After relapse 35% of patients have symptoms resistant to most antipsychotic drugs. Clozapine is one of the most effective antipsychotic drugs and is the drug of choice for treatment-re- sistant patients. At the same time, its application could be limited by poor tolerance in majority of patients, especially in the initial treatment period. There is alarge individual variety in effective doses of clozapine.Objective. Assessment of clinical relevance of clozapine blood plasma concentration in patients with episodic schizophrenia in partial remission of poor quality.Materials and methods. Twenty five patients (7 men, 18 women) average age of patients with diagnosis of episodic schizophre- nia in partial remission of poor quality with persistent severe residual psychotic disorders in the form of both delusional and/orпсихиатрия 4`2015 hallucinatory symptoms (paranoid schizophrenia, incomplete remission - F20.04 in ICD-10), who were prescribed clozapine, were included into the study. The average age of the patients was 41 ± 11 years, disease duration was 13 ± 8,6 years, age of onset was 28 ± 7,4 years. The main inclusion criterion was as follows: at least one of two items of PANSS, «Delusions» and «Hallucinatory be- havior», should be of mild or more severe degree (three points and higher). Blood sampling was carried out in the period between the seventh and tenth day of receiving by a patient a therapeutic dose of clozapine. Measurement of clozapine level was performed with mass spectrometry in the laboratory of pharmacokinetics MHRC, Clinical and psychometric (PANSS, CGI-S) assessment was done on the 7-th to 10-th and 28-th days of medication. Side effects were registered with UKU scale.Results. Average index of PANSS composite score for the moment of blood sampling amounted 94,9 ± 13,9, positive symptoms subscale - 23,2 ± 5. Average index for the item «Delusions» was 4,5 ± 1,04. For the item «Hallucinatory behavior» it was - 3,9 ± 1,15. Negative symptoms subscale was 24,2 ± 4 and general psychopathology subscale - 47,6 ± 8. Average level clinical global impression according to CGI-S was 4 ± 0,7 points. Average dose of clozapine was 245 mg/day (min. 100 mg/day, max. 700 mg/day). Plasma20 level of clozapine «hit» into the therapeutic window in 4 patients (16%), while in 15 patients (60%) it was lower and in 6 (24%) - higher than therapeutic levels. In two patients (8%) the concentration exceeded the toxic level. After 3 weeks of treatment andВопросы клинической и биологической психиатрии in 2 weeks after the blood sampling the patients with normal drug concentration (3 patients), had PANSS scores lower than in the groups with abnormal concentration. The patients with low plasma level of clozapine (13 patients) had lower PANSS scores than the patients with a high concentration (4 patients). Average number of side-effect cases caught by UKU scale per group was 2,35 ± 3,7: for patients with normal concentration it was - 3 ± 3,6, for low concentration - 0,38 ± 1,12, for high concentration - 8,25 ± 3. Significant moderate interrelation between the number of side-effects and both with dose ( r = 0,52) and with concentration in plasma ( r = 0,63) was found. The dose-dependent side effects included sedation, tachycardia, hypotension, dizziness.Conclusion. Optimal dose adjustment of clozapine according to clinical data only is a very difficult task. Optimal clinical efficacy and tolerability especially in the initial period of treatment may be achieved by accurate dose correction under control of plasma level of the drug. Information on clozapine plasma level could be helpful for individualizing of medication starting with the be- ginning of treatment in everyday practice.

шизофрения, неполная ремиссия, клозапин, концентрация, schizophrenia, partial remission, clozapine, plasma concentration

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