Adding or Switching Antipsychotic Medications in Treatment-Refractory Schizophrenia

Abstract

Objective-This study compared patients with schizophrenia whose antipsychotic medications were switched to manage treatment-resistant positive psychotic symptoms with those for whom another antipsychotic was added. Psychiatrists' characteristics and perceptions of effectiveness of the medication change on clinical outcomes were also reported.Methods-Psychiatrists participating in a nationally representative mailed survey (N=209) reported on the clinical features, management, and response to the change in antipsychotic medication (added versus switched) of one adult patient with treatment-refractory schizophrenia under their care for at least one year.Results-Thirty-three percent of patients were treated with an added antipsychotic medication. Compared with patients whose antipsychotic medications were switched, those with an added antipsychotic medication were more likely to be female, to have received care from the same psychiatrist for more than two years, and to have been recently prescribed an antidepressant. Compared with psychiatrists who switched antipsychotic prescriptions, those who added an antipsychotic reported that the change was less likely to reduce positive symptoms, improve functioning, and prevent hospitalization. Psychiatrists who added rather than switched antipsychotics reported more frequent attendance at educational programs sponsored by a pharmaceutical company. Conclusions-Consistent NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript treatment-resistant positive psychotic symptoms. In light of these findings, efforts to identify and implement more effective evidence-based pharmacologic approaches should be undertaken.A substantial proportion of patients with schizophrenia, estimated at 10% to 30% of outpatients, are considered resistant to standard antipsychotic treatment (1-3). In an inpatient population of one state psychiatric hospital, roughly one-half of patients with schizophrenia were determined to be treatment resistant on the basis of inadequate response to two different antipsychotic medication trials of at least six weeks' duration (4). Treatment-resistant patients often exhibit persistent residual disability and impaired quality of life and incur significant health care costs despite sustained adherence with antipsychotic medications (2).Clozapine is the only antipsychotic medication with demonstrated efficacy for treating positive symptoms in treatment-resistant schizophrenia (1,5,6). However, despite dissemination of evidence-based treatment guidelines for schizophrenia that strongly endorse the use of clozapine (7-9), the extent of its use in the United States remains well below the estimated prevalence of treatment-resistant schizophrenia (10,11).Clinicians faced with a patient who does not respond to or cannot tolerate standard antipsychotic therapy are left with few treatment options. One option is to switch the patient to another antipsychotic agent in hopes that its receptor profile will prove beneficial (12-14). However, a considerable...

Antipsychotic Polypharmacy in Schizophrenia

“…[35,49] For example, a multicentre audit of antipsychotic drug prescribing for inpatients in the UK [17] found that the most common clinical indication for the use of polypharmacy was the perceived failure of a single antipsychotic to control symptoms. However, this finding is somewhat at odds with the observation by Kreyenbuhl et al [42] that psychiatrists do not recognize antipsychotic polypharmacy as particularly effective in reducing psychotic symptoms or improving overall functioning. Nevertheless, to treat a poorly responsive schizophrenic illness, many psychiatrists would choose to combine two antipsychotics rather than proceed to a trial of clozapine.…”

“…Clinicians tend to switch more often than they add another antipsychotic. [42,43] But not uncommonly, if a patient's mental state improves during such a switch, the prescribing clinician may be disinclined to complete the switch because of a perceived risk of destabilizing the illness, again potentially leading to continuing antipsychotic polypharmacy. [44][45][46] In the UK, oral antipsychotic medication is co-prescribed to around half of patients receiving depot/long-acting injection preparations; [47,48] in a proportion of cases the oral antipsychotic is the same drug as the depot, a situation that would not be considered as use of combined antipsychotics, although this practice is still a major contributor to high antipsychotic dosage.…”

Antipsychotic polypharmacy – confusion reigns

“…In practice, clinicians appear to perceive antipsychotic polypharmacy to be ineffective for persistent, treatmentresistant positive psychotic symptoms. 13 The combination of typical and atypical antipsychotics seems to produce a typical response (i.e. high rates of movement disorder).…”

Prescribing trends in treatment-resistant schizophrenia

“…As there was no effect of age/experience of prescribers on the choice of prescription, it can be speculated that prescription habits may get inherited from the senior clinicians. In a similar survey done in the US, it was found out that psychiatrists who added rather than switched antipsychotics reported more frequent attendance at educational programmes sponsored by pharmaceutical companies [19]. There was no evidence of influence of pharmaceutical industry on the choice of treatment in this sample.…”

“…In a similar survey carried out in the US, looking into only treatment-resistant cases, 33% of cases were on combination therapy comparing to 46.1% in this sample [19]. Although the frequency of antipsychotic polypharmacy was found to vary according to patient, illness, setting and provider variables, rates in schizophrenia commonly were reported to range from 7% to 50% [13,20].…”