OBJECTIVES: The study purpose was to evaluate cost effectiveness for the treatment with some Depot neuroleptics (Decanoate Zuclopenthixol, Decanoate Flupenthixol, Palmitate Pipothiasine) for patients with schizophrenia (ICD-10) in Moscow community psychiatric outpatient clinic compared with oral forms of conventional neuroleptics. METHODS: In the frame of the first (clinical) stage a 24-weeks mirror-image cost effectiveness study was performed. Three cohorts of 34, 29 and 29 patients at high risk of relapses or frequent exacerbation of schizophrenic symptoms and consequent hospitalizations was treated with Decanoate Zuclopenthixol, Decanoate Flupenthixol, Palmitate Pipothiasine, respectively. Clinical improvement were evaluated with PANSS ? CGI, and dynamic of social functioning and quality of life of patients with original checklist. Severity of extrapyramidal side effects was evaluated with Simpson-Angus Scale. Cost analysis was performed including relevant data about the direct and indirect costs (rub. 1998) for all of the patients. At the second (analytic) study stage by means of decision tree simulation model an economic evaluation of treatment with the Depot neuroleptics over a hypothetical five-year period was performed. RESULTS: Statistically significant clinical improvement along with improvement of social functioning and quality of life of all of the patients receiving depot were achieved. Economic analysis indicated significant (50%) saving in the total medical cost associated with the patients despite the fact that these medicines have a higher acquisition cost. Twice as much gain has reached from societal perspective. Analytic method confirms that the long- term treatment with the Depot antipsychotics is cost effectiveness versus oral standard ones. CONCLUSIONS: The treatment of schizophrenia with studied Depot neuroleptics should be considered as an evidence based (first line) maintenance strategy in usual practice setting especially for outpatients with problems of compliance.