Patient characteristics, burden and pharmacotherapy of treatment-resistant schizophrenia: results from a survey of 204 US psychiatrists

Background: Minimal/non-response to antipsychotic treatment, and persistent positive symptoms despite treatment, are common among patients with schizophrenia. The aim of this study was to characterize a US treatment-resistant schizophrenia (TRS) population in terms of patient demographics, burden of symptoms, treatment history, and factors influencing therapeutic choice.

Methods: In an online survey, 204 psychiatrists self-selected and completed three patient records: two TRS and one schizophrenia ('non-TRS').

Results: Respondents reported that 29.5% of their schizophrenia caseload had TRS. Selected TRS (n = 408) vs non-TRS (n = 204) patients were more likely to be unemployed (74.5% vs 45.1%, p < 0.001), hospitalized at least once (93.4% vs 74.0%, p < 0.001), and to have physical/psychiatric comorbidities including obesity (40.2% vs 23.5%, p < 0.001) and depression (38.7% vs 25.0%, p = 0.001). Psychiatric symptoms were more frequent and severe in TRS, and interfered more with social and functioning domains. Of positive symptoms, eliminating delusions and hallucinations was considered most important to improve a patient's long-term prognosis. In TRS, clozapine monotherapy was the most common treatment (15.9%), though ranked fifth of ten options to treat TRS. Psychiatrists typically increased the antipsychotic dose or added a second antipsychotic before initiating clozapine or switching antipsychotics. Antipsychotic switches were most commonly due to lack of efficacy (TRS = 71.4% vs non-TRS = 54.3%, p < 0.001) and intolerability (34.4% vs 38.4%, p = 0.22) with the prior antipsychotic. Persistent hallucinatory behavior was the top symptom leading to treatment switches in TRS (63.9% vs 37.1%, p < 0.001).

Conclusions: According to psychiatrists, symptoms have a greater clinical burden on patients with TRS than non-TRS. TRS is commonly managed by antipsychotic dose increases/combinations, with clozapine the fifth preference despite being the only approved TRS medication. New treatments are needed for patients who do not respond to available antipsychotics.