Clozapine discontinuation in early schizophrenia: a retrospective case note review of patients under an early intervention service

Abstract

Aim:Research in patients with treatment-resistant schizophrenia has demonstrated that clozapine discontinuation is associated with poor outcomes. There is, however, a paucity of research investigating the impact of clozapine discontinuation specifically in younger patients with more recent onset schizophrenia. A case note review was therefore conducted to ascertain medium-term prognoses in patients with treatment-resistant schizophrenia under an early intervention service (EIS) following clozapine discontinuation.Methods:The case notes of 25 patients under the care of Birmingham EIS who discontinued clozapine were examined retrospectively. Reasons for discontinuation were recorded. Clinical outcomes including total duration of inpatient or home treatment admission, antipsychotic dose, number of alternative antipsychotics prescribed and adverse events were recorded for both the year before and the year after stopping clozapine. Statistical comparisons of pre- and post-discontinuation clinical outcomes determined whether discontinuation had negative effects.Results:There was no significant difference between the pre- and post-discontinuation clinical status following clozapine discontinuation. More than half (56%) of patients remained stable after stopping clozapine. Mean inpatient or home treatment stay rose from 29.7 to 62.6 days (p = 0.155), total antipsychotic dose from 50.1% of British National Formulary (BNF) limits to 60.5% (p = 0.627), number of alternative antipsychotics prescribed from 1.28 to 1.80 (p = 0.186), number of hospital/home treatment episodes from 0.20 to 0.44 (p = 0.083) and number of adverse events from 0 to 0.20 (p = 0.059). Non-compliance was the main reason for discontinuation (44%, n = 11).Conclusions:This is the first clozapine discontinuation study specifically considering EIS patients. Discontinuation did not lead to significant effects on 1 year outcomes, though the study is underpowered. These findings may be used to inform future prospective cohort discontinuation studies.

Clinical Outcomes after Clozapine Discontinuation in Patients with Schizophrenia: A Systematic Review

“…The number of patients in each study was 106 in one RCT 13 ; 190 in one retrospective study 12 ; 1,008 in one mirror-image study 26 ; 2,250 in one retrospective cohort study 17 ; and small sample sizes (n<100) for the remaining studies. All studies included patients with schizophrenia spectrum disorders, 12 14 16 18 19 23 23 25 27 32 32 34 37 exclusively included patients with TRS, two 11 35 included both patients with TRS and non-TRS, and 14 12 13 15 17 20 20 22 26 28 28 29 31 36 37 did not clearly state whether patients had TRS or non-TRS ( Table 1 ).…”

“…The mean duration of clozapine treatment varied considerably from weeks to years. Among the 18 studies 11 11 11 12 14 16 19 21 22 24 25 27 28 30 32 32 33 34 36 that stated reasons for clozapine discontinuation, we classified the reasons into the following six categories: inefficacy, intolerance, nonadherence, patient or clinician decision, study design, and other. Among the 15 studies 11 13 15 18 20 23 28 28 30 32 33 35 35 37 that described a clozapine discontinuation strategy, six studies 18 29 30 32 37 reported abrupt discontinuation and nine studies 11 13 15 20 23 28 33 35 36 reported gradual discontinuation ( Table 1 ).…”

A Case Report of Excessive Use of Clozapine Combined With Clonazepam

“…In addition, it is the only effective drug for refractory schizophrenia. However, although CLZ is effective in treating psychosis, it may need to be discontinued in several cases such as pericarditis ( 11 ), agranulocytosis, and antipsychotic malignant syndrome ( 12 ). In addition, there may be a variety of withdrawal reactions such as autonomic nervous system symptoms, psychosis, gastrointestinal tract and serotonin discontinuation symptoms during drug withdrawal ( 5 ).…”

Clozapine discontinuation withdrawal symptoms in schizophrenia

“…8 In some circumstances, clozapine has been discontinued successfully after symptom remission. 9 , 10 …”

“…8 In some circumstances, clozapine has been discontinued successfully after symptom remission. 9,10 Since the widespread use of clozapine, it has been recognised that stopping clozapine can lead to marked deterioration in clinical status in patients. Whilst this has been attributed largely to a relapse of the underlying mental disorder, it has become increasingly recognised that this may also be attributable to clozapine withdrawal symptoms.…”