S1. CLOZAPINE RECHALLENGE FOLLOWING NEUTROPENIA USING GRANULOCYTE COLONY-STIMULATING FACTOR: A QUEBEC CASE SERIES
Bibliographic record
Abstract
Abstract Background Clozapine possesses unique efficacy profile in treatment-resistant schizophrenia but is associated with neutropenia and agranulocytosis, in respectively, 3% and 0.7% of exposed patients. Granulocyte colony-stimulating factor (G-CSF) has been used to allow clozapine continuation or rechallenge in such situation (1,2). Methods We aim to describe the use of G-CSF to maintain clozapine despite neutropenia or agranulocytosis in treatment resistant schizophrenia patients in Quebec province, Canada. A national clozapine hematological monitoring database was consulted to identify all patients who have had red event (neutrophil count < 1,5 threshold) since 2004 in Quebec and was cross-referenced with hospital pharmacy software to identify patients who have received at least one dose of G-CSF while been exposed to clozapine All patients with an active cancer diagnosis while taking clozapine and G-CSF were excluded. A group of pharmacists specialized in psychiatry in Quebec was also contacted to ensure selecting all cases in the province. In additional to demographic data and clozapine and G-CSF details, Clinical Global Impression severity scale (CGI-S) was used to evaluate psychopathology severity during four critical turning points: before and after clozapine introduction, after agranulocytosis episode and after clozapine rechallenge. All data were collected retrospectively, using patient’s medical files, from January to July 2019. Results Eight (8) patients (5 males, 3 females), Caucasian, mean age 48 years old, with clozapine median exposition of 4.8 years, were identified. In 7/8 of those, G-CSF was used according to an “as required strategy”, i.e., whenever the patient’s neutrophil count dropped below a pre-determined threshold, varying according to patient between 0,8 à 1,5. In the other patient, a 3-weekly doses were preventively administered. Despite this, a mean number of 4 red events (ranging from 1 to 10 events) were subsequently observed in those patients, leading to clozapine cessation in 4/8 patients. One other patient responded to G-CSF but the clinical team felt uncomfortable to maintain clozapine in such circumstances. No complication (infection for instance) due to low neutrophil counts was observed nor any significant side effect related to G-CSF. However, in all these cases, while clozapine treatment was associated with clinically significant improvement of psychopathology (mean CGI-S decreased from 5.5 to 3.4), clozapine cessation led to an important psychotic deterioration (mean CGI-S of 6.2) at follow up. Fortunately, in patients successfully rechallenged (3/8), a strong clinical improvement was observed, with return to previous response level observed. Discussion To our knowledge, this is the largest case series of clozapine rechallenge using G-CSF and adds to the 39 already described cases in which G-CSF was concomitantly used with clozapine (1,2). While an “as required” strategy was mainly used here, a different prophylactic G-CSF use may have led to higher rates of clozapine maintenance, despite red codes, which provides the impetus for further studies. Reference
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.003 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.010 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".