© 2021 Informa UK Limited, trading as Taylor & Francis Group.Objectives: One-third of the patients with schizophrenia show treatment resistance and literature on the effectiveness of interventions in patients with persistent symptoms is conflicting. This study aimed to assess clinical preferences of clinicians in those showing treatment resistance to antipsychotics and to determine correlates of interventions. Methods: Treatment strategies applied in the patients with schizophrenia in daily practice were inquired retrospectively. Those showing poor response to at least two antipsychotics and were administered a clinical intervention in a University Hospital between January and September 2018 were included. Clinical correlates of distinct interventions were evaluated. Results: The most common intervention (47%) was transition to a long-acting injectable antipsychotic (LAIA) and the second most common (22%) was addition of a second/third oral drug to on-going oral therapy. Switching to clozapine was more effective on positive symptoms comparing with the other interventions (p < 0.01). LAIA therapy showed a superiority over oral antipsychotic interventions at improving positive symptoms, except clozapine (p < 0.01). Conclusions: LAIA administration and oral antipsychotic augmentation were the most common interventions in the patients with persistent symptoms. Clozapine was related to better clinical improvement in the present study and it might be administered as a second-line treatment in schizophrenia.Key points Effectiveness of the treatment strategies in schizophrenia patients with persistent symptoms is not satisfactory to meet expectations of the clinicians yet. Clozapine still seems to be the best option to provide a favourable improvement in TRS. LAIA and oral AP combination are used frequently in schizophrenia for persistent psychotic symptoms and targets of the combination therapies in daily practice needs to be clarified. The most common intervention was transition to a LAIA (47%) in the study and none of the patients administered LAIA had used a long-acting AP before the intervention. High rate of treatment nonadherence in schizophrenia is an important reason for common LAIA preference in the patients with persistent symptoms. Growing evidence indicates that clozapine can be used as a second-line treatment in schizophrenia, and thus, there is an urgent need to increase clozapine use in the patients with persistent symptoms in clinical practice.