Perspectives of clozapine-naïve outpatients with treatment-resistant schizophrenia on clozapine commencement: a mixed-methods convergent study.

objectivesThis study aimed to investigate the perspectives of clozapine-naïve outpatients with treatment-resistant schizophrenia on clozapine commencement and the barriers and facilitators of it.

designA mixed-methods convergent design was employed using both qualitative and quantitative data on the same items.

settingIn-home visits or meetings at three Mental Health outpatient facilities in Region Zealand East, Denmark.

participantsClozapine-eligible, yet clozapine-naïve, outpatients with schizophrenia. A convenience sample of 206 patients with schizophrenia treated with antipsychotic polypharmacy (APP) was screened for clozapine eligibility. Clozapine eligibility included recurrent/continued prescription of APP throughout the past year, ≥ 3 different antipsychotics (APs) trialled at a therapeutic dose and ≥2 APs trialled adequately before current treatment. All eligible patients able to provide written informed consent were invited to participate.

methodsThe participants' perspectives were assessed qualitatively through semistructured interviews and quantitatively with closed-ended questions, numerical scale ratings, and standardised patient-reported outcome measures. Moreover, the participants' sociodemographic and clinical characteristics were collected through case files, participant questionnaires, and clinical ratings made by the participants' treating clinicians. Interviews were transcribed verbatim and analysed thematically. Quantitative data were analysed with descriptive statistics. Finally, qualitative and quantitative results were compared and merged to draw meta-inferences.

resultsEighteen patients were included, 10 (56%) were men and the median age was 30.0 years (IQR 24.8-37.8). Nine participants (50%) were willing to commence clozapine if offered now, nine were not. No apparent clinical or socioeconomic differences were observed between refusers and acceptors; however, the acceptors rated their subjective recovery on the Brief INSPIRE-O significantly lower than the refusers did, and qualitatively, they all expressed subjective distress due to their current symptoms. Three themes characterised the refusers' reasons for not accepting clozapine: 'Reconciliation with the current situation warrants no change in treatment', 'Clozapine is a last-resort treatment for last-resort people' and 'Permanent or situational reluctance due to practical aspects of treatment'. In the vast majority of cases, blood sampling had little or no impact on the participants' current willingness to commence clozapine, and quantitatively, blood sampling ranked lowest of the suggested barriers, whereas hospital admission for clozapine commencement ranked highest. The adverse side effects of clozapine, sedation and, weight gain in particular, were considered a major barrier if previously encountered with ineffective AP trials. The introduction of individualised commencement plans mitigating personal barriers was highlighted as the facilitator with the greatest impact on clozapine willingness, able to turn refusals into acceptance.

conclusionsPatients tend to prefer the predictability in status quo over switching to clozapine if they previously have trialled multiple APs with inadequate symptom reduction and subsequent deterioration/rehospitalisation or AP-induced weight gain and sedation. Moreover, the impression that clozapine treatment was unmanageable or a last-resort option further accentuated their reluctance to switch. Antipsychotic-trial fatigue and the stigma of clozapine as a last-resort treatment should be avoided by adhering to guidelines, thereby limiting the number of antipsychotics trialled before offering clozapine. Fortunately, it seems as if the patient's willingness to trial clozapine is positively impressionable to the conversation about customised commencement plans offering commencement on the patient's terms. For patients with subjective distress due to their symptoms, such plans can even reverse an initial clozapine refusalCite Now.