Treatment‐resistant schizophrenia can be very difficult to manage and here the authors discuss the treatment challenges in such a patient who has a dual diagnosis of polysubstance abuse. The patient responded to the unusual combination of clozapine, sertraline, quetiapine, valproate semisodium and clonazepam but there were difficulties with the clozapine titration and augmentation. The clinical management lessons are discussed.

Treatment‐resistant schizophrenia can be very difficult to manage and a significant number of patients go through many different antipsychotic combinations with limited success. Physical health side‐effects such as diabetes, raised cholesterol levels and cardiovascular problems secondary associated with some antipsychotics may complicate a patient's treatment and enforce a difficult but necessary change of antipsychotics. Here, the authors discuss the struggle to balance mental and physical health treatments in a patient who has developed type 2 diabetes, related problems from high HbA1c and cardiac issues.