Clozapine-resistant schizophrenia – non pharmacological augmentation methods

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Clozapine is the drug of choice for drug-resistant schizophrenia, but despite its use, 30-40% patients fail to achieve satisfactory therapeutic effects. In such situations, augmentation attempts are made by both pharmacological and non-pharmacological methods. To date, most of the work has been devoted to pharmacological strategies, much less to augemantation of clozapine with electroconvulsive therapy (C+ECT), transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS).

Aim: The aim of the work is to present biological, non-pharmacological augmentation treatment methods with clozapine.

Material and methods: A review of the literature on non-pharmacological augmentation treatment methods with clozapine was made. PubMed database was searched using key words: drug-resistant schizophrenia, clozapine, ECT, transcranial magnetic stimulation, transcranial electrical stimulation and time descriptors: 1980-2017.

Results: Most studies on the possibility of increasing the efficacy of clozapine was devoted to combination therapy with clozapine + electric treatments. They have shown improved efficacy when using these two methods simultaneously from 37.5 to 100%. The only randomized trial so far has also confirmed the effectiveness of this procedure. Despite the described side effects of tachycardia or prolonged seizures, most studies indicate the safety and efficacy of combined use of clozapine and electroconvulsive therapy. Transcranial magnetic stimulation also appears to be a safe method in patients treated with clozapine. However, further research is needed before ECT can be included in standard TRS treatment algorithms. The data for combining transcranial electrical stimulation with clozapine, come only from descriptions of cases and need to be confirmed in controlled studies.

Conclusions: The results of studies on the possibility of increasing the effectiveness of clozapine using biological non-pharmacological treatment methods indicate a potentially beneficial effect of this type of methods in breaking the super-resistance in schizophrenia. Combination of clozapine and ECT can be considered as the most recommended strategy among these treatment methods.

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