The evolving definition of treatment resistance.

Despite the introduction of antipsychotic treatment for schizophrenia, the outcome for many patients has remained poor. This is largely due to the treatment-resistant nature of schizophrenia in some patients and inadequate long-term maintenance treatment. The definition of treatment resistance remains controversial in spite of its importance. This review discusses the importance of treatment resistance and the factors affecting its definition in the light of recent advances in knowledge and treatment. A decade ago, positive symptoms were thought to be the prime outcome measure for schizophrenia and were the standard by which treatment resistance was largely assessed. More recently, however, a wider range of outcome measures has been recognized, including both negative symptoms and cognitive function. All of these outcome measures affect quality of life such that the patient may consider any outcome other than a return to premorbid levels of functioning as inadequate. Furthermore, patient responsiveness should be recognized as a continuum rather than as a dichotomy of response or nonresponse; partial response to treatment may not be accepted as satisfactory. Definitions of treatment resistance should reflect these factors. Patients may benefit from pharmacotherapy with atypical antipsychotics even if they do not meet criteria for narrowly defined treatment resistance. Although clozapine use has often been restricted to treatment-resistant patients, the benefit it bestows outweighs the potential risk of side effects in patients with less stringently defined treatment resistance.