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

Abstract

BackgroundMinimal/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.MethodsIn an online survey, 204 psychiatrists self-selected and completed three patient records: two TRS and one schizophrenia (‘non-TRS’).ResultsRespondents 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).ConclusionsAccording 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.

<p>Exploration of Treatment-Resistant Schizophrenia Subtypes Based on a Survey of 204 US Psychiatrists</p>

“…This online survey revealed that, in general, patients with TRS with greater clinical burden (ie, more suicide attempts, more hospitalizations, unemployed) had greater illness severity and chronicity markers. This finding suggests that, not only is TRS a more severe form of schizophrenia,7 but that there is a gradient within the TRS population whereby patients with poorer outcomes have greater illness severity and chronicity. Whether this gradient will also reflect response or non-response to treatments with the strongest evidence-base for TRS, ie, clozapine (where the pooled non-response rate is as high as 60% according to the most recent meta-analysis24) and electroconvulsive therapy adjunct to clozapine (where the pooled non-response rate is 32–46%25), requires further study.…”

“…Demographic and clinical characteristics for the total TRS population (N=408) have been previously published 7. The following text describes patient demographic and clinical characteristics by TRS subgroup.…”

“…The survey methodology has been previously published 7. In brief, a mix of hospital-/office-based and public/private psychiatrists were approached.…”

“…Half of the psychiatrists were asked to select patient records based on their own “spontaneous” definition of TRS, whereas the other half were asked to select patient records based on a “prompted” definition of TRS, adapted from treatment guidelines 3–6. As described previously,7 the two TRS subpopulations (spontaneous and prompted definitions) were similar and thus pooled into a single TRS group.…”

“…Treatment-resistant schizophrenia (TRS) is defined in clinical guidelines as an inadequate response in target schizophrenia symptoms following treatment with two or more antipsychotics of adequate dose and duration 3–6. Patients with schizophrenia and treatment resistance have a higher burden of disease and face poorer outcomes than those without treatment resistance 7. TRS has a high societal and economic burden, and a high caregiver burden 8–11…”