Clozapine Therapy With or Without Antipsychotic Augmentation: A Retrospective Evaluation of Prescribing Practices in a Canadian Provincial Residential Treatment Centre for Concurrent Disorders: Traitement par la clozapine avec ou sans intensification à l’aide d’antipsychotiques : évaluation rétrospective des pratiques de prescription dans un centre de traitement résidentiel provincial canadien pour les troubles concomitants
Bibliographic record
Abstract
BackgroundGuidelines for treatment-resistant schizophrenia (TRS) advocate for a trial of clozapine monotherapy before the consideration of antipsychotic augmentation. Commonly cited justifications for augmentation include inadequate response to clozapine monotherapy and the potential to lower the necessary clozapine dose or serum concentration, thereby reducing dose-dependent adverse effects. Nonetheless, the degree to which these outcomes are realized in routine clinical practice, particularly among individuals with concurrent disorders, remains uncertain. This study aimed to explore the extent to which clozapine monotherapy is utilized before the initiation of antipsychotic augmentation strategies, and to assess the effects of antipsychotic augmentation on clozapine serum concentrations and the incidence of related adverse effects.MethodsWe retrospectively analyzed clinical and drug monitoring data from 80 adults with TRS and substance use disorder (SUD) comorbidity at a provincial inpatient centre for concurrent disorders. Antipsychotic augmentation was quantified using Defined Daily Dose (DDD). Generalized and linear mixed models compared the impact of monotherapy vs. augmentation on clozapine serum levels and adverse effects, adjusting for covariates.ResultsMost patients receiving antipsychotic augmentation (78%) did not have an adequate trial of clozapine monotherapy. Analysis revealed that clozapine with antipsychotic augmentation was modestly and negatively associated (B = -0.039; 95% CI = -0.078 - -0.001) with clozapine serum concentrations, particularly at higher DDD (≥2). Clozapine with antipsychotic augmentation was not associated with reduced incidence of dose-dependent adverse events (tachycardia, constipation, or overall anticholinergic medication use).ConclusionFindings from this study indicate that commonly cited rationales for combining clozapine with antipsychotic augmentation - namely, enhancing tolerability through clozapine dose reduction or mitigating inadequate response to monotherapy - are not consistently supported by real-world outcomes. These results underscore the necessity for clinical guidelines to incorporate context-sensitive recommendations that address the complexities inherent in managing individuals with TRS and comorbid SUDs, while integrating real-world considerations and the perspectives of those with lived experience.
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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 | 0.001 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.004 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".