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Background: Clozapine has a unique efficacy profile among individuals suffering from treatment-resistant schizophrenia, but is associated with hematological side effects. The use of granulocyte colony-stimulating factors (G-CSF) to allow clozapine continuation or rechallenge has emerged as a promising option, but evidence is still scarce. Aim: To describe the largest case series so far published regarding this practice. Method: A national clozapine hematological monitoring database was consulted to identify all patients who had had neutrophil count <1.5 × 109/L since 2004 in Quebec and was cross-referenced with hospital pharmacy software to identify patients who had received at least one dose of G-CSF, such as filgrastim, while being exposed to clozapine. All data were collected retrospectively, using patients’ medical files, from January to July 2019. Results: Using G-CSF, three out of eight patients could maintain clozapine despite neutropenia episodes that otherwise would have required treatment discontinuation. The only side effect reported was mild short-lived back pain, over a mean 3-year follow-up period. In all but one case, filgrastim was used on an “as-needed” basis at doses of 300 mcg administered subcutaneously. Conclusion: These results suggest that the “as-needed” use of G-CSF is well-tolerated and may allow clozapine rechallenge in some well-selected patients, adding to the paucity of data regarding long-term safety and efficacy of this strategy. More research may help to better define potential candidates and optimal regimen of such practice.

Background Although recognised as the most effective antipsychotic for treatment-resistant schizophrenia, clozapine remains underused. One reason is the widespread concern about non-adherence to clozapine because of poor adherence before initiating clozapine. Aims To determine if prior poor out-patient adherence to treatmentbefore initiating clozapine predisposes to poor out-patient adherence to clozapine or to any antipsychotics (including clozapine) after its initiation. Method This cohort study included 3228 patients with schizophrenia living in Quebec (Canada) initiating (with a 2-year clearance period) oral clozapine (index date) between 2009 and 2016. Using pharmacy data, out-patient adherence to treatment was measured by the medication possession ratio (MPR), over a 1-year period preceding and following the index date. Five groups of patients were formed based on their prior MPR level (independent variable). Two dependent variables were defined after clozapine initiation (good out-patient adherence to any antipsychotics and to clozapine only). Along with multiple logistic regressions, state sequence analysis was used as a visual representation of antipsychotic-use trajectories over time, before and after clozapine initiation. Results Although prior poor adherence to antipsychotics was associated with poor adherence after clozapine initiation, the absolute risk of subsequent poor adherence remained low, regardless of previous adherence level. Most patients adhered to their treatment after initiating clozapine (>68% to clozapine and >84% to any antipsychotics). Conclusions Despite the fact that poor adherence prior to initiating clozapine is widely recognised by clinicians as a barrier for the prescription of clozapine, the current study supports the initiation of clozapine in all eligible patients.

Background Pharmacovigilance studies have reported a higher risk of problematic gambling (PG) in people receiving aripiprazole (ARI), a partial dopamine agonist. This association needs to be specifically assessed in schizophrenia (SZ) given the high prevalence of risk factors for PG in this population (eg, comorbid substance use) and given the nature of the dopamine dysfunction in this disorder. At the present stage, case studies may shed light on such an association. Methods All published cases involving SZ patients with PG while on ARI were systematically identified. Two instruments were used to assess causality. Results We identified 16 published SZ cases exposed to ARI experiencing PG. Half of whom had a gambling history before ARI exposition. Naranjo scores led to the estimation of a possible link between ARI exposition and PG in 15 of 16 cases (average score of 3) and probable (score of 5) in 1 case. More than 50% of items were left unknown owing to the lack of information or scale limitations. Using the Liverpool algorithm, causality estimation was raised to probable in 13 of 16 cases, definite in 1 case, and nonassessable in 2 cases. Conclusions The present review confirms that ARI may be involved in the occurrence of PG in some SZ patients. However, important information to assess causality was frequently missing, and the 2 scales used did not yield the same degree of certainty. The current article calls for including more details in future case reports and for well-powered studies carefully assessing factors such as comorbid diagnoses.

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Background Aripiprazole (ARI), an antipsychotic drug used to treat various mental health disorders, has recently been associated with the emergence of problem gambling (PBG). However, few cases have been reported in the schizophrenia-related psychotic disorders population, and even fewer provided sufficient details to systematically assess the causality of the association. Methods This article describes 6 cases with first-episode psychosis in whom PBG emerged while on ARI. Detailed information was gathered from clinical staff and patients' families to systematically assess the causal link between ARI and the emergence of PBG using the Naranjo and Liverpool Adverse Drug Reaction scales. Findings Five of these cases were previously diagnosed with a substance use disorder and/or cluster B personality traits. Five had received a more potent dopaminergic antagonist treatment before being switched to ARI. Two of them had presented PBG before being diagnosed with a psychotic disorder. The level of certainty about the causal role of ARI varied from possible to certain, and in 4 cases, the 2 scales yielded different ratings. Implications Although these cases suggest that ARI may be associated with the emergence of PBG in the early course of schizophrenia-related psychotic disorders, they cannot prove the causality or the strength of this association. They provide the impetus to perform adequately powered and well-controlled prospective studies to draw more definite conclusion about the causality of this association and, in the meantime, further emphasize the need to carefully assess PBG in this population.

<b><i>Background:</i></b> There is a growing interest in understanding the impact of video games in the clinical field, given that their excessive use could be associated with health issues. Particularly, gaming disorder (GD) is considered as an addictive behavioral disorder. Clinicians widely recognize the comorbidity of gaming and psychotic disorders (PDs). Furthermore, association between addictive (i.e., substance use disorders) and PDs are well recognized by clinicians. It seems of high interest to explore GD among people with PDs. To this day, little is known about the consequences of GD in vulnerable populations. <b><i>Objectives:</i></b> The aim of this scoping review was to summarize the available research on the comorbidity between GD and PD and to identify the knowledge gaps in this field. <b><i>Methods:</i></b> We used Levac’s six-stage methodology for scoping review. Two-hundred and forty-two articles from seven databases were identified. Eight articles respected our inclusion and exclusion criteria. <b><i>Results:</i></b> No available study has assessed the prevalence or incidence of GD among patients with PDs. The cases reported highlight the possibility that excessive video gameplay or abrupt gaming disruption could trigger psychosis in some patients. <b><i>Conclusion:</i></b> The results highlight a significant lack of knowledge concerning PDs associated with GD as only a few reported cases and one empirical study exposed the potential association between those conditions.